2026-2027 NEW & CONTINUED RESEARCH GRANT RECIPIENTS/PROJECTS: 

• Jose A Adams, MD, Mount Sinai Medical Center, research study entitled: "Whole Body Periodic Acceleration (pGz) in Heart Failure". Heart failure (HF) is a serious and increasingly common condition, particularly in older adults. More than 50 out of every 1,000 people over the age of 65 are affected, and the lifetime risk of developing HF between ages 45 and 95 is as high as 20–45%. Individuals with HF often experience shortness of breath, fatigue, reduced ability to exercise, and fluid buildup in the lungs and body. Common causes include damage to the heart from prior heart attacks, as well as conditions such as diabetes and high blood pressure. Despite advances in treatment, approximately half of patients diagnosed with HF die within five years. HF also leads to more than one million hospitalizations each year in the United States and costs over $30 billion annually, making it a major public health and economic challenge. Whole Body Periodic Acceleration (pGz) is a non-invasive therapy that gently moves the body back and forth in a head-to-foot direction using a bed-like platform, similar to the motion of rocking a baby carriage. This movement creates beneficial pulses throughout the blood vessels, stimulating the release of substances that improve blood flow and support heart health. With prior support from the Miami Heart Research Institute and Florida Heart Research Foundation, our laboratory has shown that pGz can improve heart function after cardiac arrest. We have also demonstrated that using pGz before a cardiac event (a strategy known as “preconditioning”) enhances recovery and preserves heart function. This project will examine whether pGz can improve heart function in established heart failure, particularly in models that reflect the most common causes of the disease. We will also investigate how pGz works specifically whether it reduces heart scarring, inflammation, and harmful biological processes. If successful, this research could lead to a simple, non-invasive therapy that improves survival, enhances quality of life, and reduces healthcare costs for patients living with heart failure.
  
• Nanette Bishopric, MD, Georgetown University, research study entitled: “Restoration of Heart Function by Targeting Remodeling Pathways in the Ischemic and Stressed Heart”.  Cardiovascular disease remains the #1 cause of death in the US, despite remarkable advances in treatment and prevention, and heart failure affects more than 6 million Americans. Our laboratory is studying how chronic stress and inflammation lead to development of heart failure. Heart failure is not only lethal, but it also greatly reduces quality of life, leads to shortness of breath, reduced exercise capacity, and a high risk of cardiac rhythm disturbances. Heart failure has many causes, but cures are lacking, and in most cases, treatment is focused on symptom relief. Groundbreaking research in our laboratory, with the support of the MHRI, has now begun to shine light on exactly what goes wrong at the molecular and cellular level in some common forms of heart failure, leading the way to more effective treatment and reversal of this debilitating, progressive and lethal condition.  The heart is a pump made up of specialized muscle cells, called cardiac myocytes, that beat in coordination to circulate the blood. These cells are very long-lived, possibly more than 50 years, and are replaced very slowly (0.5-1% per year). Over a lifetime of continuous beating, they adapt remarkably to a range of physical and mental challenges. However, many common chronic diseases, such as high blood pressure, obesity and diabetes, generate stress that triggers inflammation, leads to abnormal function and cell death, and damages heart function. Aging by itself is an important contributor to both inflammation and cardiac damage. Our project in the lab this year is to understand how age and inflammation affect the function and survival of cardiac myocytes in the context of chronic stress. We hypothesize that chronic inflammation associated with aging and age-related disorders is responsible for damage and dysfunction of cardiac myocytes and ultimately leads to heart failure. We also hypothesize that the stress pathways we have identified and will further characterize in this year’s work will become practical targets for treatment with new types of specially-designed drugs from our collaborators at the University of Michigan. We will continue to explore the role of molecular pathways common to inflammation, cancer chemotherapy and aging through the use of genetically modified cells and animal models. We will specifically explore the effect of RAGE, a receptor for inflammatory signals, and p300, a key regulator of the heart’s response to damage, on the immune cells that control cardiac inflammation and healing. Our ultimate goal is to prevent and reverse the morbidity and mortality of age- and stress-associated heart failure. 
  
• Florida Heart Research Foundation Cardiovascular Summer Research Internship Program at FIU:  The Florida Heart Research Foundation Cardiovascular Summer Research Internship (CV-SRI) at Florida International University provides a transformative summer research experience for highly motivated high school students, incoming FIU undergraduates, and transfer students interested in cardiovascular and biomedical research. Through this immersive eight-week program, participants are paired with FIU faculty mentors conducting cutting-edge cardiovascular related research. Students gain hands-on laboratory experience while developing critical thinking, scientific communication, and professional skills essential for success in STEM careers and advanced education. The Foundation’s continued support has also allowed FIU to expand long-term undergraduate cardiovascular research opportunities through the Florida Heart Research Scholars program and the Florida Heart Undergraduate Research Fellowship. These programs provide sustained faculty mentorship, advanced research training, and ongoing professional development for undergraduate students pursuing careers in medicine, biomedical science, and related health professions. Students regularly present their research at institutional, state, and national conferences, strengthening their preparation for graduate school, medical school, and research careers. Together, these initiatives create a comprehensive research pathway that supports students from early exposure to advanced undergraduate research engagement. The partnership between the Florida Heart Research Foundation and Florida International University continues to foster innovation, discovery, and educational opportunity while helping cultivate the next generation of cardiovascular researchers, healthcare professionals, and scientific leaders.
• Florida Heart Research Foundation Cardiovascular Doctoral Student Grant Program at FIU: 
• Aasma Dahal, PhD Candidate, Florida International University, research study entitled: “Peripheral Arterial Disease Monitoring: Spatio-Temporal Near-Infrared Spectroscopy Imaging in Pre-Clinical and Clinical Studies”.  Peripheral Arterial Disease (PAD) is a serious condition caused by narrowed blood vessels, often due to calcium buildup, leading to reduced blood flow and potential amputation. Millions of people worldwide live with PAD, and it significantly lowers the quality of life. One of the major causes of PAD is the calcium buildup within the blood vessels, which makes the blood vessels stiff and less flexible, restricting healthy blood flow. Therefore, finding PAD early is important because treatment works best in early stages. However, many current diagnostic techniques like ultrasounds and angiograms are difficult to access in low-income communities and often fail to detect disease early. Some of these tests are also uncomfortable and involve harmful radiation, making them unsuitable for frequent monitoring of disease progression. To address this challenge, our team has developed a new tool called “Near-Infrared Optical Scanner (NIROS)”. NIROS is a portable, safe device that does require direct contact to the skin to detect the disease. It uses harmless near-infrared light to measure blood flow and oxygenation in the feet. Since PAD affects circulation, these measurements can reveal early signs of disease and track how it progresses over time. Our prior studies have shown that NIROS could detect abnormalities linked to calcification in mice heart by measuring blood flow changes in the tail. We now want to further evaluate it to determine whether it can detect the PAD-related changes in blood flow and oxygen. This project has the potential to transform how PAD is detected and managed. NIROS offers earlier diagnosis, simpler follow-up, personalized care, ultimately improving the quality of life for those with PAD. This technique has a potential to be a portable, triage technique for a quick assessment of blood flow and oxygenation in the legs in emergency rooms procedures.
• Katherine Kaiser, PhD Candidate, Florida International University, research study entitled: "Defining the Role of Caveolin-1 Localization in Tissue-Specific Calcification Mechanisms”.  Calcium mineral formation is essential for building strong, healthy bones, but when calcium builds up inside blood vessels it can become dangerous and increase the risk of heart disease. Although both bone and blood vessels can accumulate calcium mineral, this project explores the idea that these tissues use fundamentally different cellular mechanisms to control mineral formation. This research focuses on a protein called caveolin-1 (CAV1), which appears to play opposite roles in the mineral formation of bone cells and vascular cells. Using advanced methods to study cell membranes, proteins, and signaling pathways, this project will investigate how the location of CAV1 within cells and its interaction with another signaling protein called ERK can influence how calcium minerals form. By improving our understanding of how mineralization differs between bone and blood vessels, this work aims to help identify new strategies to prevent harmful vascular calcification while preserving the healthy mineralization needed for strong bones.
• Perony Nogueira, PhD Candidate, Florida International University, research study entitled: "Developmental origin of elastin producing cells and mechanism underlying elastogenesis in the murine aortic valve". Every day, your heart's aortic valve opens and closes about 100,000 times, a tireless doorway between the heart's main chamber and the artery that carries oxygen to your entire body. To survive that endless motion without tearing, this valve is woven with elastin, a stretchy protein that acts like the heart's built-in rubber bands. When elastin fails, valves stiffen or leak, and in rare genetic conditions like Williams-Beuren Syndrome and Supravalvular Aortic Stenosis, children are born without enough of it, leaving their major heart vessels dangerously narrowed from the very start of life. Surprisingly, the same cells that color our skin and hair, also called melanocytes, also live inside the aortic valve. Their job there has long been mysterious. Both these pigment cells and many of the valve's structural cells share a common origin: a remarkable embryonic population called neural crest, which travels through the developing body to build tissues as different as facial bones, nerves, and skin pigment producing cells. To test whether this lineage is responsible for the valve's elastin, we used genetically engineered mice in which the elastin gene was switched off only in neural crest cells. Our data showed that their valves contained significantly less elastin, identifying neural crest cells as major architects of these rubber bands. When we studied albino mice, whose pigment pathway is broken, their valves had noticeably less elastin, as if the stage crew had walked off the job. When we treated these albino mice with L-DOPA, a small molecule already used safely in medicine for decades, the missing elastin came back. This discovery opens a tangible door: repurposing a familiar, well-tolerated drug as a possible therapy to treat people with elastin-deficient valves, giving their hearts back the resilience they were never able to build on their own.
• Manuel Perez, PhD Candidate, Florida International University, research study entitled: "Flow-Induced Conditioning of Stem Cells for the Production of Cardioprotective Exosomes”.   Stem cells are especially important in biology because they have natural ways to protect themselves from stress and damage. One way they do this is by releasing special proteins that help keep them—and other cells—healthy. Interestingly, when gentle pressure or movement is applied to stem cells, they react by producing proteins that can help protect the heart. These helpful proteins are packaged into tiny vesicles called exosomes. Exosomes act like messengers that travel between cells, carrying signals that promote healing. They have been shown to help heart cells survive, reduce damage, fight inflammation, and even help grow new blood vessels. Our research is focused on finding ways to encourage stem cells to release more of these healing exosomes. We’re exploring how moving fluids, like the flow of blood, can “activate” the stem cells and cause them to produce more exosomes. This could be especially useful for repairing hearts damaged by blocked blood flow during a heart attack, a condition known as ischemia. In our lab, we use a system that lets us control how the fluid flows over the stem cells. By adjusting the flow, we are identifying the ideal conditions that trigger the stem cells to release the most beneficial exosomes. If we can determine how to reliably produce these exosomes, we could create a new kind of treatment to help repair hearts damaged by disease.
•  Alexi Switz, PhD Candidate,  Florida International University, research study entitled: “Development and Characterization of Helically Coiled Conductive Electrospun Fibers for Cardiac Patch Application”.  Every 40 seconds, someone has a heart attack. Right now, the only approved way to fix the damage caused by a heart attack is through a heart transplant. But since there aren’t enough donors and transplants can be risky, scientists are looking for other solutions. One idea is a cardiac patch—a kind of “living band-aid” that could repair the damaged heart. To make this patch, we are using a process called electrospinning to create two kinds of fibers. The first type looks like rows of tiny Slinkys, and the second type looks like pencils stacked neatly in a case. The slinky-shaped fibers might help the patch bend and move with the beating of the heart. Conductive particles will also be added to the fibers, since the heart uses electrical signals to beat. We plan to test how these fibers work, including how well they work with heart cells. The goal is to create a patch that could help heal heart damage in the future.
• Florida Heart Research Foundation Cardiovascular Doctoral Student Grant Program at FSU:
• Gallage Ariyaratne, PhD Candidate,  Florida State University, research study entitled: "The Role of Non-Canonical NFkB Signaling in Arrhythmogenic Cardiomyopathy".  Arrhythmogenic Cardiomyopathy, or ACM, is an inherited form of heart disease that is a primary cause sudden cardiac death in young individuals. Presently, disease management focuses on symptomatic control using pharmacologic agents (e.g., antiarrhythmics) or invasive interventions, such as the placement of implantable cardioverter defibrillators (ICDs). Sadly, these interventions do not target underlying mechanisms that contribute to chronic heart inflammation in patients with ACM, ultimately leading to heart failure. Recently, it has become more evident that these chronic inflammatory reactions are mediated by a protein (NFκB) that is often considered the “master regulator of inflammation.” In cardiomyocytes (aka, heart cells) from patients with ACM, NFĸB is a major driver of inflammatory disease processes that contributes to disease progression in ACM. NFĸB triggers the release of pro-inflammatory mediators that drives local, heart inflammation, but also recruits immune effector cells (aka, white blood cells) like neutrophils and macrophages to the heart in large numbers. These infiltrating immune cells can cause heart injury, cardiac dysfunction, and potentially lethal arrhythmias. Therefore, the objectives of this project are to elucidate the molecular and cellular mechanisms by which heart cells send signals to immune cells and influence their trafficking to the heart and induce myocardial inflammation. By elucidating NFĸB-mediated pathways that cause heart inflammation, fibrosis, cardiac dysfunction and remodeling, and electrical instability, it may be possible to determine which disease processes are responsible for maintaining chronic heart inflammation. As such, results from this project may uncover new pharmacologic targets – at the molecular level – that selectively block NFĸB-mediated signaling pathways, without suppressing the innate immune response. In summation, project outcomes aim to target the root causes of cardiomyocyte injury and shielding the heart from chronic inflammation that leads to heart failure.
• Ronnie Chastain, PhD Candidate, Florida State University, research study entitled: "The Role of the C-domain of Troponin C in Health and Development of Cardiomyopathic Disease".  Over the past decade, more evidence has accumulated implicating myofilament-related mechanisms in the progression of heart disease. Investigating these mechanisms has uncovered different mutations or changes to sarcomere proteins, such as the troponin (Tn) complex of the thin filament or other proteins involved with myofilament function, that can lead to early developments in cardiac related-disease progression. The Tn complex resides on the thin filament of sarcomeres, the functional unit of muscles, where it regulates the contractile ability of the muscle fiber in a Calcium (Ca2+)-dependent manner. Tn is comprised of three different proteins: TnI, TnT, and TnC. TnC is the Ca2+-binding subunit of the complex and the cardiac (cTnC) isoform has three Ca2+-binding sites (II, III, IV); Ca2+ binding to site II (N-domain) ‘activates’ contraction whereas sites III and IV (C-domain) always have the divalentcations Mg2+ or Ca2+ bound. My research will revolve around characterizing the mouse models that have mutations which block the ability of Ca2+ to bind the ‘structural binding sites’ of cTnC of the C-domain. After which, we will explore any biochemical or physical alterations to the myofilament to expand our understanding of the structural and modulatory elements involved in cardiac muscle regulation. To investigate these possible changes, I will use various techniques such as skinned fiber mechanics, small-angle x-ray diffraction, echocardiogram and others to understand the different force- Ca2+ relationships, sarcomere alterations, and cardiac dysfunction in our models. The information that can be garnered with this research will help increase our knowledge of cardiac muscle, which can lead to the resolution of better therapeutic targets or new modes of identification for early cardiac disease progression.
• Paula Nieto Morales, PhD Candidate,  Florida State University, research study entitled: "Investigating the role of TNNC1 in Pediatric Dilated Cardiomyopathy".  Dilated cardiomyopathy (DCM) is the most common cardiomyopathy in children, with nearly 40% of symptomatic pediatric DCM (PDCM) cases resulting in heart transplantation or death within two years. PDCM involves the enlargement and weakening of the heart muscle, leading to impaired systolic function and heart failure. While the disease's clinical severity is well recognized, its molecular mechanisms remain complex and poorly understood. Most cases are idiopathic or familial, involving mutations in over 30 genes. Recently, a rare variant in TNNC1, which encodes cardiac troponin C (cTnC), has been linked to PDCM. Nevertheless, the specific pathophysiology underlying this variant has yet to be fully elucidated. Utilizing a newly developed mouse model, we characterized disease progression from the organ level down to the sarcomere, identifying a robust DCM phenotype as early as four weeks of age. Our findings highlight significant remodeling in myofilament calcium sensitivity and intracellular calcium handling. A central focus of this study is the evaluation of a novel small-molecule myosin activator, currently in Phase II clinical trials for adults. Specifically, we will evaluate the in vivo effectiveness of this activator post β-adrenergic stimulation. These in vivo assessments are paired with muscle mechanics studies using permeabilized fibers pre-treated with protein kinase A (to mimic β-adrenergic stimulation) to determine if the observed physiological benefits are achieved by directly correcting biophysical deficits at the myofilament level. Although this molecule was designed to target thick-filament mutations, our research suggests that activating the thick-filament molecular motor can provide therapeutic benefit for cardiomyopathies caused by thin-filament defects.
•  Chunming Dong, MD, University of Miami, research study entitled: "The Use of CRISPR Interference (CRISPRi) Technology to Prevent Acute and Chronic Rejection in Organ Transplantation."   Organ transplantation using organs from the same species (allograft transplantation) remains the most effective treatment for patients with end-stage heart, lung, liver, and kidney diseases. Although advances in surgical techniques and immunosuppressive therapies have significantly improved patient outcomes, acute rejection (AR) and chronic rejection (CR) continue to be major causes of graft failure. In heart transplantation, chronic rejection often manifests as cardiac allograft vasculopathy, a progressive narrowing of the coronary arteries that can ultimately lead to graft dysfunction and failure. To prevent rejection, transplant recipients must remain on lifelong immunosuppressive medications, which increase their risk of serious infections, malignancies, and other complications. Therefore, developing strategies that reduce the immune response to transplanted organs while minimizing the need for long-term immunosuppression would provide substantial clinical benefits.  With the continued support of the Miami Heart Research Institute (MHRI), Dr. Dong's laboratory has made significant progress toward addressing the root cause of transplant rejection—alloimmunity. In previous funding cycles, the laboratory successfully utilized CRISPR-Cas9 genome-editing technology to suppress major histocompatibility complex (MHC) class I and class II molecules, the primary triggers of immune recognition and rejection. Using a novel dual sgRNA approach, the team demonstrated efficient suppression of these molecules in endothelial cells and experimental transplantation models, resulting in reduced alloimmune responses and improved graft survival in mice. The laboratory subsequently extended this work to human leukocyte antigens (HLA), the human equivalent of MHC molecules, and successfully reduced HLA-ABC and HLA-DR expression in human cells. Although CRISPR-Cas9 has proven to be a powerful and effective gene-editing tool, its reliance on permanent genomic modification presents potential challenges for clinical translation, including concerns regarding off-target effects and long-term safety. To overcome these limitations, Dr. Dong's laboratory has transitioned to CRISPR interference (CRISPRi), an innovative gene-regulation technology that suppresses gene expression without altering the underlying DNA sequence. CRISPRi utilizes a catalytically inactive (dead) Cas9 protein (dCas9) linked to a transcriptional repressor, allowing genes to be turned down in a reversible and highly controlled manner while preserving genomic integrity.  The current project focuses on suppressing HLA Class I molecules (HLA-ABC), which play a critical role in activating immune responses against transplanted organs using CRISPRi. The research team will use novel guide RNAs targeting the promoter regions of HLA-A, HLA-B, and HLA-C genes. Their preliminary studies showed substantial reduction of HLA-A both at transcription and protein levels, providing feasibility for the proposed approach. Importantly, this suppression was achieved without permanently modifying the genome, representing a potentially safer and more clinically applicable approach than conventional gene editing. The laboratory is currently expanding this strategy to target HLA-B, HLA-C and HLA-DR, with the long-term goal of simultaneously suppressing both HLA Class I and Class II pathways that are major players in immune activation. Successful completion of this work could significantly reduce the need for prolonged immunosuppressive therapy, decrease transplant-related complications, and transform the field of transplantation medicine. Ultimately, this technology may lead to the development of less immunogenic donor organs, reducing the need for lifelong immunosuppression and improving long-term transplant outcomes. 
• Lina Shehadeh, PhD,  University of Miami, research study entitled: "Cardiolipin Remodeling as a Driver of Mitochondrial Dysfunction in Heart Failure with Preserved Ejection Fraction".  Understanding and Treating Heart Failure with Preserved Ejection Fraction: Over 6 million Americans suffer from a form of heart failure called HFpEF (heart failure with preserved ejection fraction), where the heart becomes stiff and cannot relax properly between beats. Despite being responsible for half of all heart failure cases, there are currently no effective treatments. Patients experience severe shortness of breath, fatigue, and have a life expectancy of only 5 years after diagnosis. Dr. Lina Shehadeh and her team at the Miami Heart Research Institute have discovered promising clues in animal models: the heart's energy-producing powerhouses—called mitochondria—appear to be damaged in HFpEF. Specifically, the protective membranes surrounding these mitochondria become abnormal, potentially causing them to rupture and release toxic substances into the heart muscle. This damage may prevent the heart from generating enough energy to function properly. The research team identified a protein called Gasdermin D that may play a key role in this mitochondrial damage. Their preliminary studies in mice suggest that when animals develop obesity, diabetes, or high cholesterol, Gasdermin D becomes overactive and creates holes in the mitochondria, potentially triggering a cascade of problems that leads to heart stiffness and failure. The exciting prospect: Gasdermin D can potentially be blocked by an FDA-approved drug called dimethyl fumarate (DMF), currently used to treat multiple sclerosis. Because this drug has already been proven safe in humans for other conditions, it could potentially move to clinical testing faster than developing a completely new medication—if the animal studies prove successful.  What the researchers will do: First, they will study mice with HFpEF to test the hypothesis that mitochondrial damage drives disease progression and determine whether DMF can prevent it. Second, they will analyze blood samples from 273 heart failure patients to investigate whether simple blood tests might one day detect mitochondrial damage, potentially allowing doctors to diagnose the condition earlier and monitor treatment effectiveness. Third, they will test DMF in pigs, which have hearts very similar to humans, using the same advanced imaging and heart function tests used in patients. These large animal studies are a critical step toward determining whether this approach could work in humans.  Why this matters: This research represents an important step toward developing the first effective treatment for HFpEF. If the hypothesis proves correct in both mouse and pig models, it could pave the way for human clinical trials within 2-3 years—dramatically faster than typical drug development timelines. Additionally, if the blood biomarkers under investigation prove useful, they could eventually help doctors identify which patients might benefit most from treatment, enabling personalized medicine approaches. Beyond HFpEF, this research may also provide insights for patients with diabetes-related heart disease and other conditions where mitochondrial damage appears to play a role.  This project offers hope for developing new treatments for millions of Americans living with a currently untreatable disease by testing whether an existing safe medication could be repurposed for HFpEF, based on promising findings from laboratory and animal models.
• Roberta Lassance-Soares, PhD, University of South Florida, study entitled: "“Ischemic-Trained Extracellular Vesicles Reprogram Monocytes and Improve Hindlimb Ischemia Outcomes”.  Critical limb ischemia (CLI) is a severe form of vascular disease in which the arteries supplying the leg become blocked, causing extreme pain, poor wound healing, and a high risk of amputation. Many patients cannot undergo surgical procedures to restore blood flow, leaving them with very limited treatment options. New approaches that help the body naturally repair blood vessels are urgently needed to prevent limb loss and improve quality of life. Our recent work shows that when blood flow is temporarily reduced in a controlled setting (a single ischemia insult), the body releases tiny particles into the bloodstream called extracellular vesicles (EVs). These EVs carry signals that “reprogram” immune cells, specifically monocytes, making them less inflammatory and able to better contribute to blood vessel growth. This blood vessel growth, called neovascularization, is a natural process that improves blood flow in the limb. In this project, we will study whether EVs collected from mice subjected to an ischemia insult can reprogram monocytes in other mice, improving blood flow and healing after a limb blockage. First, we will determine whether these EVs change monocyte function inside the body. Then, we will test whether giving these EVs to mice with poor circulation improves recovery and reduces tissue damage. By understanding how these EVs help blood neovascularization, this research may lead to a new, non-invasive therapy for patients with CLI. This approach has the potential to reduce amputations, improve patient outcomes, and offer new hope to individuals with limited treatment options. Ultimately, this study can be the first step to using those EVs to improve cardiovascular health for people across Florida and beyond.
  
  

2025-2026 NEW & CONTINUED RESEARCH GRANT RECIPIENTS/PROJECTS: 

• Sonya Natalie Tuerff, MD (Principal Investigator),  Memorial Hospital, Memorial Healthcare System, project entitled: "Empowering Access: Enhancing Vascular Health for Underserved Women in Broward County, FL".  This project strives to help women in South Florida who are at high risk for heart and vascular problems. Many of these women face major obstacles that make it difficult to stay healthy, such as a lack of reliable transportation, childcare duties, or challenges to their immigration status. Doctors at Memorial Healthcare System are seeing a disturbing increase in serious health issues among these women, including severe diabetic foot wounds, uncontrolled high blood pressure, and a low rate of adherence to prescribed treatments. This project tackles the problem by combining vascular health screenings with existing community outreach programs. We plan to screen at least 500 women from under-resourced areas over one year for Peripheral Artery Disease (PAD), diabetes, and hypertension, addressing not only their physical health but also the social and psychological factors that impact it. At every interaction, women will be taught about their health conditions so they can better understand their results and what steps they can take to stay healthy. Finally, the project will create a "toolkit" that other hospitals and healthcare systems can use to replicate this successful model.
•  LaPrincess C. Brewer, MD (Project Lead), Mayo Clinic Jacksonville, project/study entitled: "FAITH! Emergency Preparedness Initiative".  The FAITH! Emergency Preparedness Initiative is a community-driven project focused on improving emergency response and health outcomes among African-American churches in Jacksonville, Florida, with a special emphasis on cardiac emergencies like sudden cardiac arrest. Research shows that Black and Hispanic individuals are much less likely than their white counterparts to receive lifesaving CPR from bystanders during cardiac emergencies. This gap means lower survival rates for these communities. The COVID-19 pandemic also hit African-American communities especially hard, highlighting the need for better emergency preparedness and health education. The FAITH! program first began in Minnesota, partnering with local churches to promote heart health and emergency readiness. We created culturally tailored resources, trained church leaders known as “Prevention Champions”, and built emergency preparedness teams (EPTs) within churches. The program also offered CPR and AED training and shared health information through newsletters and webinars. Encouraged by the success in Minnesota, FAITH! expanded to Jacksonville. Our team recruited 19 local churches, trained leaders, and hosted webinars on emergency preparedness. We also provided Spiritual First Aid certification to church pastors and Prevention Champions. Each church received a $500 grant to improve their emergency plans and was asked to showcase how they used the funds. As we continue to partner with Jacksonville churches, we intend to provide AEDs to each of the 19 churches and host CPR/AED training for pastors and Prevention Champions in collaboration with the local American Heart Association affiliate. A post-doctoral research fellow will be hired to engage with the churches and work to share findings among the community and academic outlets. By empowering churches and their leaders, FAITH! helps communities become more resilient in emergencies, especially cardiac events. The program also addresses broader health disparities and builds stronger networks for sharing lifesaving information and resources.
• Demilade Adedinsewo, MD, Mayo Clinic Jacksonville, research study entitled: "Evaluating ElectroCardioGram based Artificial Intelligence predictions across device types (ECG-AI)". Utilizing artificial intelligence to analyze the 12-lead electrocardiogram (ECG), a first line diagnostic test for detection of heart disease, has enhanced the ECGs ability to accurately predict multiple cardiac disorders. The use of artificial intelligence in this context currently exceeds human-level interpretation of the ECG test. Despite its remarkable performance, there are significant challenges with scaling this technology and making it accessible to all for cardiovascular care. This is often due to differences in ECG data configuration, formats, and storage practices across health care institutions within the United States. The overall goal of this study is to develop and establish a process for extraction and integration of digital ECG signals from multiple devices, thus making novel artificial intelligence algorithms more accessible so patients can benefit equitably from this technology, facilitate data sharing/transfer, and support dataset curation for development of newer prediction algorithms.
• Joshua Hutcheson, PhD (Principal Investigator) & Prem Chapagain, PhD, Jin He, PhD & Francisco Fernandez-Lima, PhD (Co-Investigators), Florida International University, research study entitled: "A Nanoanalytical Approach to Unraveling Differences Between Physiological and Pathological Mineralization". Calcification, the buildup of calcium mineral, commonly occurs in two places: during natural bone formation and in diseased blood vessels. Calcification of major vessels that distribute blood from the heart to the body, known as arteries, serves as a predictor of future heart problems and even death. Bone-like mineral buildup can cause heart attacks and make arteries stiff, putting more strain on the heart. Interestingly, the more mineral found in arteries, the less in bones, and vice versa—a phenomenon known as the "calcification paradox." Accordingly, individuals with weaker bones tend to have more mineral in their arteries. However, we still do not fully understand how minerals form in each tissue. The study focuses on nano-sized structures called calcifying extracellular vesicles (EVs), which play a role in mineral formation. By comparing how these EVs form and function in bone cells versus artery cells, the study seeks to uncover differences in their makeup and behavior that can provide new insight into the origins of the calcification paradox. Ultimately, this research could lead to better understanding of mineral formation in both tissues and potentially influence future treatments for conditions like osteoporosis and cardiovascular disease.
• Florida Heart Research Foundation Cardiovascular Summer Research Internship Program at FIU:  The Florida Heart Research Foundation Cardiovascular Summer Research Internship (CV-SRI) at Florida International University offers a transformative summer research experience for highly motivated high school students and incoming FIU undergraduates. Participants are paired with FIU faculty conducting cutting-edge cardiovascular research and gain exposure to laboratory techniques, critical thinking, and scientific communication. This immersive program provides professional development workshops and early access to the world of biomedical research. In addition to the summer experience, the Foundation’s continued support has allowed FIU to expand longer-term cardiovascular research opportunities for undergraduates through one- and two-year research fellowships. These students, recognized as Florida Heart Research Scholars and Florida Heart MARC Fellows, are mentored by faculty and conduct sustained cardiovascular research. The students participate in weekly professional development workshops and present at scientific conferences to increase their preparation for graduate studies, medical training, and careers in biomedical research. These Florida Heart Research initiatives form a strong pathway to cultivate the next generation of cardiovascular researchers and clinicians, advancing the Foundation’s mission of fostering innovation, discovery, and education in heart health.
• Anamika Prasad, PhD (Principal Investigator) & Darryl Dickerson, PhD (Co-Investigator),  Florida International University, research study entitled: "Advancing Regenerative Approaches for Myocardial Infarction through a Standardized ex-vivo Diagnostic Platform for Cardiac Patches".  Myocardial infarction or heart attack causes lasting damage to the heart and leads to long-term health challenges due to the heart's limited repair capacity. Cardiac patches are a promising regenerative approach for repairing and recovering heart function. This research aims to fast-track cardiac patch treatment by developing a standardized diagnostic platform to systematically evaluate the effectiveness of cardiac patch features impacting heart support and regenerative capacity. The research goals are achieved by creating patches with tunable mechanical properties and a cost-effective 3D-printed dynamic testing environment, which will be together used to assess cell-loaded patch viability and regenerative capacity. By addressing critical limitations in current patch designs and developing a unifying enabling technology for evaluating the effectiveness of tissue-engineered solutions, this research will enhance the translation of cardiac patches from bench to bedside, ultimately improving heart health, extending life, and reducing the burden of heart failure.
• 2025 Junior Faculty Researcher: Valentina Dargam, PhD, Florida International University, research study entitled: "Modeling Lead and Cadmium Cardiotoxicity: Understanding How Exposure Levels Influence Cardiovascular Disease Onset and Progression.”  Lead and cadmium are widespread environmental contaminants absorbed through the respiratory and gastrointestinal tracts. Both metals have been linked to increased cardiovascular risk and were recently classified as independent risk factors for cardiovascular disease by the American Heart Association, with evidence suggesting that even low-level exposure can significantly elevate risk. This study will develop preclinical models to investigate how different doses and durations of lead and cadmium exposure affect cardiac and vascular remodeling. Through a combination of invasive and noninvasive techniques, researchers will measure blood pressure, vascular resistance, and cardiac function to identify exposure thresholds that induce hypertension and cardiac dysfunction in mice. Findings from this research will improve our understanding of how chronic exposure to environmental metals contributes to the development and progression of cardiovascular disease.
• Florida Heart Research Foundation Cardiovascular Doctoral Student Grant Program at FIU: 
• Abeer Al Barghouthi, PhD Candidate, Florida International University, research study entitled: “The Role of 3D Multiscale Biophysical Cues on the Maturation Advancement of Induced Pluripotent Stem Cell-Derived Cardiomyocytes” . Heart disease is still the leading cause of death around the world. Right now, there are no treatments that can regrow the heart tissue damaged during a heart attack. A promising direction we are exploring is using lab-grown heart cells called induced pluripotent stem cell-derived cardiomyocytes (iCMs). These cells have the potential to fix damaged heart tissue. As of now, iCMs don’t look or behave exactly like the real heart cells found in the body. They aren’t fully developed and don’t have the complex structure that real heart cells do. Real heart cells, called cardiomyocytes (CMs), live in a 3D environment inside the body, surrounded by a structure called the extracellular matrix (ECM). They respond to different biophysical signals from this environment. In our research, we want to understand how these 3D surroundings help iCMs grow and become more like real heart cells. We aim to understand how different biophysical signals affect iCMs and help them mature. Our goal is to learn how to use these signals to create stronger, more realistic lab-grown heart tissues for future treatments.
• Yih-Mei Lin, PhD Candidate, Florida International University, research study entitled: "Development of Physiological Cardiac Patch for Diminishing Adverse Events of Ischemic Heart Injury”. In recent decades, researchers have developed a powerful tool called human-induced pluripotent stem cells (iPSCs). These special cells can be made from a person’s skin or blood and turned into almost any type of cell in the body. One exciting use of iPSCs is creating heart cells—called cardiomyocytes (iPSC-CM)—which can be used to study heart disease, test new medicines, and even help treat heart conditions in the future. However, these lab-grown heart cells often do not fully mature like real heart cells in the body, which limits how useful they are for research and therapy. To solve this problem, researchers are using soft, 3D materials called hydrogels. These hydrogels are designed to mimic the natural environment of the heart and can be adjusted in their stiffness and flexibility, which affects how the heart cells grow and develop. In this study, we are building a 3D hydrogel system to test how different levels of stiffness and stretchiness influence the growth and maturity of iPSC-derived heart cells. Our ultimate goal is to create more realistic heart tissue in the lab to improve research and develop better treatments for heart disease.
• Perony Nogueira, PhD Candidate, Florida International University, research study entitled: "Developmental origin of elastin producing cells and mechanism underlying elastogenesis in the murine aortic valve". Cells similar to the ones that give our skin its color and protect us from the sun's harmful UV rays are also found inside our heart valves. Surprisingly, scientists are still trying to understand why these pigment-producing cells, called melanocytes, exist in the heart. Heart valves are crucial, since they open and close more than 40 million times each year. They ensure blood rich in oxygen flows correctly from your heart to the rest of your body without going backward. Our research recently discovered that these heart melanocytes help produce elastin, a protein that gives heart valves the flexibility they need to open and close smoothly. Interestingly, we also learned that the melanocytes in the heart valves don't all come from the same place as the ones in our skin. This suggests they have a unique origin during the development of the heart. Understanding exactly where these cells come from and what role they play can help doctors detect and treat heart valve diseases that are present at birth and might also offer clues for other diseases affecting the heart valves later in life.
• Manuel Perez, PhD Candidate, Florida International University, research study entitled: "Flow-Induced Conditioning of Stem Cells for the Production of Cardioprotective Exosomes”.   Stem cells are especially important in biology because they have natural ways to protect themselves from stress and damage. One way they do this is by releasing special proteins that help keep them—and other cells—healthy. Interestingly, when gentle pressure or movement is applied to stem cells, they react by producing proteins that can help protect the heart. These helpful proteins are packaged into tiny vesicles called exosomes. Exosomes act like messengers that travel between cells, carrying signals that promote healing. They have been shown to help heart cells survive, reduce damage, fight inflammation, and even help grow new blood vessels. Our research is focused on finding ways to encourage stem cells to release more of these healing exosomes. We’re exploring how moving fluids, like the flow of blood, can “activate” the stem cells and cause them to produce more exosomes. This could be especially useful for repairing hearts damaged by blocked blood flow during a heart attack, a condition known as ischemia. In our lab, we use a system that lets us control how the fluid flows over the stem cells. By adjusting the flow, we are identifying the ideal conditions that trigger the stem cells to release the most beneficial exosomes. If we can determine how to reliably produce these exosomes, we could create a new kind of treatment to help repair hearts damaged by disease.
• Alexi Switz, PhD Candidate, Florida International University, research study entitled: “Development and Characterization of Helically Coiled Conductive Electrospun Fibers for Cardiac Patch Application”.  Every 40 seconds, someone has a heart attack. Right now, the only approved way to fix the damage caused by a heart attack is through a heart transplant. But since there aren’t enough donors and transplants can be risky, scientists are looking for other solutions. One idea is a cardiac patch—a kind of “living band-aid” that could repair the damaged heart. To make this patch, we are using a process called electrospinning to create two kinds of fibers. The first type looks like rows of tiny Slinkys, and the second type looks like pencils stacked neatly in a case. The slinky-shaped fibers might help the patch bend and move with the beating of the heart. Conductive particles will also be added to the fibers, since the heart uses electrical signals to beat. We plan to test how these fibers work, including how well they work with heart cells. The goal is to create a patch that could help heal heart damage in the future.
• Jose A Adams, MD, Mount Sinai Medical Center, research study entitled: "Whole Body Periodic Acceleration (pGz) in Heart Failure". Heart failure (HF) is a devastating problem which occurs in more than 50 per 1000 individuals greater than 65 years of age. The lifetime risk of heart failure from ages 45 through 95 years is 20-45%. The symptoms of HF are varied but include; shortness of breath, easy fatigue, intolerance to exercise, fluid retention, and congestion of the lungs. The causes of HF include; scarring of the heart due to previous heart attack, uncontrolled diabetes and hypertension, genetics and other still unknown causes. Death from HF remains at approximately 50% within 5 years of diagnosis. Additionally, HF accounts for over 1 million hospitalizations annually. Furthermore, the total cost of HF in the US exceeds $30 billion annually, making HF a significant public health problem and economic burden. Whole Body Periodic Acceleration (pGz) is the back and forth motion of the body in a head to foot direction utilizing a bed like platform. The motion is similar to “a mother pushing a baby carriage back and forth”. The pGz motion induces pulsations to the body in the in all blood vessels, liberating beneficial substances from the cells which line these vessels. Previous grant support from the Miami Heart Research Institute/Florida Heart Research Foundation have allowed our laboratory to show that pGz improves the function of the heart after cardiac arrest. Additionally, pGz performed before (pre-conditioning) cardiac arrest or a heart attack, improved recovery, and heart function when compared with no treatment. This project investigates the use of pGz in models of the most common causes of HF. The study will determine whether or not pGz will improve heart function after established HF and will seek to determine if such improvements in heart function are related to the effects of pGz on heart scarring, excess inflammation, and other biochemical pathways. The findings of this study when applied to populations with HF could have a tremendous impact in reducing death, improving quality of life, and reducing healthcare costs in those affected by HF. 
• Florida Heart Research Foundation Cardiovascular Doctoral Student Grant Program at FSU
• Ronnie Chastain, PhD Candidate, Florida State University, research study entitled: "The Role of the C-domain of Troponin C in Health and Development of Cardiomyopathic Disease".  Over the past decade, more evidence has accumulated implicating myofilament-related mechanisms in the progression of heart disease. Investigating these mechanisms has uncovered different mutations or changes to sarcomere proteins, such as the troponin (Tn) complex of the thin filament or other proteins involved with myofilament function, that can lead to early developments in cardiac related-disease progression. The Tn complex resides on the thin filament of sarcomeres, the functional unit of muscles, where it regulates the contractile ability of the muscle fiber in a Calcium (Ca2+)-dependent manner. Tn is comprised of three different proteins: TnI, TnT, and TnC. TnC is the Ca2+-binding subunit of the complex and the cardiac (cTnC) isoform has three Ca2+-binding sites (II, III, IV); Ca2+ binding to site II (N-domain) ‘activates’ contraction whereas sites III and IV (C-domain) always have the divalentcations Mg2+ or Ca2+ bound. My research will revolve around characterizing the mouse models that have mutations which block the ability of Ca2+ to bind the ‘structural binding sites’ of cTnC of the C-domain. After which, we will explore any biochemical or physical alterations to the myofilament to expand our understanding of the structural and modulatory elements involved in cardiac muscle regulation. To investigate these possible changes, I will use various techniques such as skinned fiber mechanics, small-angle x-ray diffraction, echocardiogram and others to understand the different force- Ca2+ relationships, sarcomere alterations, and cardiac dysfunction in our models. The information that can be garnered with this research will help increase our knowledge of cardiac muscle, which can lead to the resolution of better therapeutic targets or new modes of identification for early cardiac disease progression.
• Paula Nieto Morales, PhD Candidate, Florida State University, research study entitled: "Investigating the role of TNNC1 in Pediatric Dilated Cardiomyopathy". Dilated cardiomyopathy (DCM) is the most common cardiomyopathy in children, with nearly 40% of symptomatic cases resulting in heart transplantation or death within two years. Pediatric dilated cardiomyopathy (PDCM) involves the enlargement and weakening of the heart muscle, leading to impaired systolic function and heart failure. While the disease's severity is well known, its molecular genetics are complex and poorly understood. Most pediatric cardiomyopathies are idiopathic or familial, involving mutations in over 30 genes. Recently, rare variants in TNNC1, which encodes cardiac troponin C (cTnC), have been linked to PDCM, although the underlying mechanisms are not well studied. This study aims to investigate the role of TNNC1 in PDCM using a new knock-in mouse model and human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs). Additionally, the study will assess the therapeutic potential of a novel myotropic drug to modulate contractility. Preliminary data from the mouse model show a DCM phenotype at four weeks of age assessed by echocardiography, with increased heart size and left ventricular dimensions confirmed by histopathology. Since cTnC is a major cytosolic calcium buffer, further research will examine if calcium regulation of the myofilament and intracellular calcium handling are altered in these mice and hiPSC-CMs. Understanding how rare genetic variants affect myocardial processes offers insights into the structural and functional roles of heart proteins. This study aims to uncover conserved pathogenic pathways, validate the mouse model's translational relevance, and identify potential therapeutic targets for precision medicine in PDCM.
• Nanette Bishopric, MD, Georgetown University, research study entitled: “Restoration of Heart Function by Targeting Remodeling Pathways in the Ischemic and Stressed Heart”. The heart is able to pump because it is made up of specialized muscle cells (=cardiac myocytes) that beat spontaneously and respond to the body’s constantly changing demands for blood supply. These cells are very long-lived. Over a lifetime of continuous beating, they adapt dynamically to changes in body size, hormonal state, and activity, and successfully meet a variety of acute challenges, ranging from mental stress to tennis matches to marathons. Many common chronic diseases, such as high blood pressure and diabetes, also cause persistent and ongoing stress that can lead to damaged function and heart failure. Despite recent success in treatment and prevention of heart attacks, cardiovascular disease continues to be the #1 cause of death in the US, as it has been since the middle of the last century. The reason is the increasing frequency of heart failure – particularly the kind known as Heart Failure with Preserved Ejection Fraction (HFpEF). More than 3 million people in the United States are living with this kind of heart failure. Heart attacks weaken the ability of the heart to pump. In contrast, HFpEF prevents the heart from relaxing. This means that it takes higher pressure to fill it with blood for the next beat. The abnormal pressure is felt in all the filling systems of the heart, especially the lungs. This in turn leads to shortness of breath, reduced exercise capacity, and a high risk of atrial fibrillation. Recognized only recently as a disorder, the incidence of HFpEF is increasing rapidly along with its major known causes: obesity, physical inactivity, diabetes, high blood pressure, and old age. Aging is also a powerful risk factor for cancer, thus cancer treatments are frequently given in the setting of HFpEF, increasing the risk of heart failure. There is no known cure and no specific treatment for HFpEF, although symptoms can be relieved with daily medication. It is increasing apparent that inflammation is an important feature of many of these conditions, and a likely common factor in their harmful cardiac effects. Groundbreaking research in our laboratory, along with others, has now begun to shine light on exactly what goes wrong at the molecular and cellular level in HFpEF, leading the way to more effective targeting and reversal of this debilitating and eventually fatal condition. In this ongoing project, we are working to understand the causal relationship between chronic stress and HFpEF. We hypothesize that inflammation is one component of a maladaptive molecular response involving that impairs the ability of the heart muscle to relax. With the multi-year support of the Miami Heart Research Institute, we have been able reveal a network of biochemical pathways in the stressed heart cell and have designed and tested novel structurally-designed molecules to reverse the process of HFpEF. In the current year of funding, we will continue to explore the role of molecular pathways common to inflammation, cancer chemotherapy and aging through the use of genetically modified cells and animal models. We will specifically explore the roles of RAGE, a receptor for inflammatory signals, and p300, a key regulator of the heart’s response to damage in the context of toxins such as cancer chemotherapy. Our ultimate goal is to prevent HFpEF-related morbidity and mortality, as well as to reverse it.
• Esther Lutgens, MD, Mayo Clinic Rochester, research study entitled: “Blocking CD40-TRAF6 interactions in macrophages to ameliorate atherosclerosis: validation and mechanistic evaluation of the 2nd generation CD40-TRAF6 small molecule inhibitors”.   The underlying cause of the majority of cardiovascular diseases is atherosclerosis, a lipid-driven chronic inflammatory disease that affects mid- and large-sized arteries. Due to the formation of atherosclerotic plaques, life-threatening atherothrombotic events, including myocardial infarction or stroke may arise when these plaques rupture or erode. Recent clinical trials have revealed that lowering inflammation is an important strategy to combat cardiovascular disease. However, these anti-inflammatory immunotherapies were not developed specifically for cardiovascular disease and therefore exhibited suboptimal efficacy and induced unwanted side effects, including infections. We have developed small molecule inhibitors that target CD40, an important immune modulator. We showed that treatment with these drugs ameliorated atherosclerosis without causing side effects in laboratory models. In this project, we aim to optimize our CD40-inhibitors for ‘in human treatment’ to enable the development of safe, anti-inflammatory therapies to combat atherosclerotic disease. 
  
• Joerg Herrmann, MD, Mayo Clinic Rochester, research study entitled: "TACTIC - TrAstuzumab Cardiomyopathy Therapeutic Intervention with Carvedilol Trial".   This study looks at how to protect the hearts of breast cancer patients who are receiving a drug called trastuzumab, which can sometimes cause heart problems. The researchers want to find out if a heart medication called carvedilol can help prevent these issues. They divided 219 patients into three groups: one group receives carvedilol only if their heart function drops below a certain level, another group receives carvedilol if there are early signs of heart damage, and the third group starts taking carvedilol before beginning trastuzumab treatment. The study is now closed to new patients, but they are still following the current participants to see which approach works best.
• Joerg Herrmann, MD, Mayo Clinic Rochester, research study entitled: “CAncer Survivor CArdiomyopathy DEtection (CASCADE)”. This study focuses on cancer survivors who have been treated with a type of chemotherapy called anthracyclines, which can increase the risk of heart problems even years after treatment. The researchers want to find the best and most cost-effective way to monitor these patients for heart issues. They test two methods: an artificial intelligence (AI) analysis of heart activity (ECG) and a blood test for a heart disease marker (NT-pro-BNP). They also look at whether using both tests together would be more effective. The study, which includes 114 patients, has finished enrolling new participants. The results will help determine the best way to keep an eye on the heart health of cancer survivors and catch any problems early. 

2023-2024 NEW & CONTINUED RESEARCH GRANT RECIPIENTS/PROJECTS: 

• Joshua Hutcheson, PhD (Principal Investigator) & Prem Chapagain, PhD, Jin He, PhD & Francisco Fernandez-Lima, PhD (Co-Investigators), Florida International University, research study entitled: "A Nanoanalytical Approach to Unraveling Differences Between Physiological and Pathological Mineralization".   Calcification, the buildup of calcium mineral, commonly occurs in two places: during natural bone formation and in diseased blood vessels. Calcification of major vessels that distribute blood from the heart to the body, known as arteries, serves as a predictor of future heart problems and even death. Bone-like mineral buildup can cause heart attacks and make arteries stiff, putting more strain on the heart. Interestingly, the more mineral found in arteries, the less in bones, and vice versa—a phenomenon known as the "calcification paradox." Accordingly, individuals with weaker bones tend to have more mineral in their arteries. However, we still do not fully understand how minerals form in each tissue. The study focuses on nano-sized structures called calcifying extracellular vesicles (EVs), which play a role in mineral formation. By comparing how these EVs form and function in bone cells versus artery cells, the study seeks to uncover differences in their makeup and behavior that can provide new insight into the origins of the calcification paradox. Ultimately, this research could lead to better understanding of mineral formation in both tissues and potentially influence future treatments for conditions like osteoporosis and cardiovascular disease.
• Joshua Hutcheson, PhD & Meghan Martin, PhD (Principal Investigators), Florida International University, research study entitled: "A Novel Small Molecule Therapy for Late-Stage Atherosclerosis".   This study aims to explore a novel treatment strategy for cardiovascular diseases, especially those involving vascular calcification, by targeting a hormone called relaxin and its receptor, RXFP1. Relaxin is known for its critical role in helping the maternal cardiovascular system adapt during pregnancy, such as increasing blood volume and improving vascular flexibility. Remarkably, these changes are reversible after childbirth, making pregnancy a unique model for understanding large-scale tissue remodeling in adults. By studying how relaxin facilitates these transformations, this study hopes to uncover new ways to treat pregnancy-related vascular complications. Additionally, this knowledge could pave the way for innovative therapies for broader cardiovascular conditions, such as hardened or calcified blood vessels that currently lack effective reversal treatments. The research involves two main goals. First, we will investigate how activating RXFP1 can prevent or even reverse vascular calcification, the deposition of bone-like mineral in late-stage vascular disease. Second, we will study the role of RXFP1 during pregnancy-related cardiovascular changes, helping us identify key molecular mechanisms linked to vascular remodeling and postnatal recovery. By understanding these mechanisms, this research could lead to breakthrough treatments not only for women experiencing complications during or after pregnancy but also for vascular diseases in the general population, addressing critical gaps in cardiovascular care.
• Florida Heart Research Foundation Cardiovascular Summer Research Internship Program at FIU: The annual Summer Research Internship program at FIU pairs motivated high school students and incoming FIU students with cardiovascular researchers, offering these students an immersive experience in innovation during their summer break. This program also encourages matriculation into undergraduate research following their summer experience. Through generous support from the Florida Heart Research Foundation, we have expanded the FIU MARC U*STAR program. MARC U*STAR is an NIH-funded training program for undergraduate students. Students within MARC U*STAR are paired with faculty mentors and complete two-year long research projects that prepare them for graduate school. The Florida Heart Research Foundation funding will specifically support MARC U*STAR affiliate students performing cardiovascular research with FIU faculty. Following this intensive training in cardiovascular research from high school through their undergraduate careers, students emerge well-poised to make substantial impacts in cardiovascular research and medicine in academic graduate programs, medical training, and/or industry.
• Florida Heart Research Foundation Cardiovascular Doctoral Student Grant Program at FSU:
• Sediqua Bufford, PhD Candidate, Florida State University, research study entitled: "Transriptomics Signature of African-American vs Caucasian Human Heart Tissue: the first step to the understanding of cardiovascular health disparities".  The overall goal is to utilize translational research to discover and target potential genes that can be used as a biomarker to advance clinical therapies to close the gap of reported mortalities due to cardiovascular disease. With a keen understanding of the urgency and significance of addressing health disparities within this population, we are ecstatic about the potential opportunity to collaborate while utilizing cutting-edge research initiatives that aim to unravel the complexities of cardiovascular health disparities. We will investigate if there is a correlation in genetic profiles based on sex and race. In Aim 1 we will study the transcriptomic profiling of the human heart evaluating the potential for different gene expression signatures in heart tissue obtained from African-American vs Caucasian individuals, including potential sex differences as well. Aim 2 involves studying physiology and disease at the cellular level using human inducible pluripotent stem cells derived cardiomyocytes (hiPSC-CMs). These hiPSC-CMs experiments will include samples from multiple individuals, i.e., African-American males and females, and Caucasian males and females. The first step will be to determine if the contractile profile of hiPSC-CMs differ based on race and sex. Subsequently, we will leverage the data obtained in Aim 1 to identify genes that may be associated with distinct contractile behaviors within our variable groups. The benefits of using hiPSC-CMs to investigate human heart disease is a comprehension of disease mechanisms, more specific drug development, and the advancement of precision medicine with the ability to identify distinct characteristics among different population groups. The goal of this project is to generate fundamental data intended for the development of more targeted treatments designed for a population currently suffering from significantly elevated mortality rates. 
• Paula Nieto Morals, PhD Candidate,  Florida State University, research study entitled: "Investigating the role of TNNC1 in Pediatric Dilated Cardiomyopathy".   Dilated cardiomyopathy (DCM) is the most common cardiomyopathy in children, with nearly 40% of symptomatic cases resulting in heart transplantation or death within two years. Pediatric dilated cardiomyopathy (PDCM) involves the enlargement and weakening of the heart muscle, leading to impaired systolic function and heart failure. While the disease's severity is well known, its molecular genetics are complex and poorly understood. Most pediatric cardiomyopathies are idiopathic or familial, involving mutations in over 30 genes. Recently, rare variants in TNNC1, which encodes cardiac troponin C (cTnC), have been linked to PDCM, although the underlying mechanisms are not well studied. This study aims to investigate the role of TNNC1 in PDCM using a new knock-in mouse model and human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs). Additionally, the study will assess the therapeutic potential of a novel myotropic drug to modulate contractility. Preliminary data from the mouse model show a DCM phenotype at four weeks of age assessed by echocardiography, with increased heart size and left ventricular dimensions confirmed by histopathology. Since cTnC is a major cytosolic calcium buffer, further research will examine if calcium regulation of the myofilament and intracellular calcium handling are altered in these mice and hiPSC-CMs. Understanding how rare genetic variants affect myocardial processes offers insights into the structural and functional roles of heart proteins. This study aims to uncover conserved pathogenic pathways, validate the mouse model's translational relevance, and identify potential therapeutic targets for precision medicine in PDCM. 
• Joerg Herrmann, MD,  Mayo Clinic Rochester, research study entitled: "TACTIC - TrAstuzumab Cardiomyopathy Therapeutic Intervention with Carvedilol Trial".   Breast cancer patients undergoing trastuzumab treatment are at risk of heart function decline or heart failure symptoms, but it is unknown if, when, and for how long cardiovascular protective strategies, e.g. with a beta-blocker, could help. This study randomly assigns those taking curative-intent trastuzumab to the beta-blocker carvedilol—either when significant heart function decline or subtle early signs of heart injury (either by elevation of a cardiac blood biomarker, i.e. cardiac troponin, or by an abnormal heart ultrasound marker, i.e. global longitudinal strain) are noted, or preventatively before beginning trastuzumab therapy. This study will further randomly assign those patients on carvedilol in these three groups to either discontinue at the end of trastuzumab therapy or to continue for another year, providing much needed clinical trial data on what the best strategy (“tactic”) for those at risk of cardiotoxicity with trastuzumab therapy is.
• Joerg Herrmann, MD, Mayo Clinic Rochester, research study entitled: “CAncer Survivor CArdiomyopathy DEtection (CASCADE)”.   Currently, there are over 15 million cancer survivors in the United States, and this number is projected to exceed 20 million within the next five years-- most of whom will be long-term survivors (5+ years). Many of these individuals are at a high lifetime risk of developing heart disease due to their exposure to anthracycline-based chemotherapy during cancer treatment. The most efficient and cost-effective way to monitor, predict and prevent the development of heart failure in these cancer survivors is not known. While echocardiography has been the standard approach, serial studies are costly and require logistics, time and effort, kindling interest in identifying less expensive cardiac surveillance strategies that can be implemented over long periods of time to a large population at risk. The current application’s objective is to assess and optimize the diagnostic performance of novel artificial intelligence (AI) electrocardiography (ECG) and an established blood marker for heart disease (NT-pro-BNP) for the detection of an abnormal heart function in cancer survivors and to compare and combine these two tests to define the most optimal strategy. These studies will inform cardiac surveillance efforts for clinical practice and the planning of a randomized clinical trial to address the clinical impact of optimal cardiac surveillance. 
• Nanette Bishopric, MD, Georgetown University, research study entitled: “Restoration of Heart Function by Targeting Remodeling Pathways in the Ischemic and Stressed Heart”.  The heart is able to pump because it is made up of specialized muscle cells (=cardiac myocytes) that beat spontaneously and respond to the body’s constantly changing demands for blood supply. These cells are very long-lived. Over a lifetime of continuous beating, they adapt dynamically to changes in body size, hormonal state, and activity, and successfully meet a variety of acute challenges, ranging from mental stress to tennis matches to marathons. Many common chronic diseases, such as high blood pressure and diabetes, also cause persistent and ongoing stress that can lead to damaged function and heart failure. Despite recent success in treatment and prevention of heart attacks, cardiovascular disease continues to be the #1 cause of death in the US, as it has been since the middle of the last century. The reason is the increasing frequency of heart failure – particularly the kind known as Heart Failure with Preserved Ejection Fraction (HFpEF). More than 3 million people in the United States are living with this kind of heart failure.  Heart attacks weaken the ability of the heart to pump. In contrast, HFpEF prevents the heart from relaxing. This means that it takes higher pressure to fill it with blood for the next beat. The abnormal pressure is felt in all the filling systems of the heart, especially the lungs. This in turn leads to shortness of breath, reduced exercise capacity, and a high risk of atrial fibrillation. Recognized only recently as a disorder, the incidence of HFpEF is increasing rapidly along with its major known causes: obesity, physical inactivity, diabetes, high blood pressure, and old age. Aging is also a powerful risk factor for cancer, thus cancer treatments are frequently given in the setting of HFpEF, increasing the risk of heart failure. There is no known cure and no specific treatment for HFpEF, although symptoms can be relieved with daily medication. It is increasing apparent that inflammation is an important feature of many of these conditions, and a likely common factor in their harmful cardiac effects. Groundbreaking research in our laboratory, along with others, has now begun to shine light on exactly what goes wrong at the molecular and cellular level in HFpEF, leading the way to more effective targeting and reversal of this debilitating and eventually fatal condition. In this ongoing project, we are working to understand the causal relationship between chronic stress and HFpEF. We hypothesize that inflammation is one component of a maladaptive molecular response involving that impairs the ability of the heart muscle to relax. With the multi-year support of the Miami Heart Research Institute, we have been able reveal a network of biochemical pathways in the stressed heart cell and have designed and tested novel structurally-designed molecules to reverse the process of HFpEF. In the current year of funding, we will continue to explore the role of molecular pathways common to inflammation, cancer chemotherapy and aging through the use of genetically modified cells and animal models. We will specifically explore the roles of RAGE, a receptor for inflammatory signals, and p300, a key regulator of the heart’s response to damage in the context of toxins such as cancer chemotherapy. Our ultimate goal is to prevent HFpEF-related morbidity and mortality, as well as to reverse it.
• Jose A Adams, MD, Mount Sinai Medical Center, research study entitled: "Whole Body Periodic Acceleration (pGz) in Heart Failure". Heart failure (HF) is a devastating problem which occurs in more than 50 per 1000 individuals greater than 65 years of age. The lifetime risk of heart failure from ages 45 through 95 years is 20-45%. The symptoms of HF are varied but include; shortness of breath, easy fatigue, intolerance to exercise, fluid retention, and congestion of the lungs. The causes of HF include; scarring of the heart due to previous heart attack, uncontrolled diabetes and hypertension, genetics and other still unknown causes. Death from HF remains at approximately 50% within 5 years of diagnosis. Additionally, HF accounts for over 1 million hospitalizations annually. Furthermore, the total cost of HF in the US exceeds $30 billion annually, making HF a significant public health problem and economic burden. Whole Body Periodic Acceleration (pGz) is the back and forth motion of the body in a head to foot direction utilizing a bed like platform. The motion is similar to “a mother pushing a baby carriage back and forth”. The pGz motion induces pulsations to the body in the in all blood vessels, liberating beneficial substances from the cells which line these vessels. Previous grant support from the Miami Heart Research Institute/Florida Heart Research Foundation have allowed our laboratory to show that pGz improves the function of the heart after cardiac arrest. Additionally, pGz performed before (pre-conditioning) cardiac arrest or a heart attack, improved recovery, and heart function when compared with no treatment. This project investigates the use of pGz in models of the most common causes of HF. The study will determine whether or not pGz will improve heart function after established HF and will seek to determine if such improvements in heart function are related to the effects of pGz on heart scarring, excess inflammation, and other biochemical pathways. The findings of this study when applied to populations with HF could have a tremendous impact in reducing death, improving quality of life, and reducing healthcare costs in those affected by HF. 
• Jose R. Lopez, MD,  Mount Sinai Medical Center, research study entitled: “Cardioprotection in Diabetic Cardiomyopathy via upregulation of ATP-sensitive K+ channels”.  Diabetes is a major public health problem that represents a huge health concern for Americans and the global population. Studies estimate that the number of people living with diabetes today ranges from 415 million to 425 million, and currently, 1.5 million deaths are attributed to diabetes worldwide every year. There are two main types of diabetes, type 1 (T1D) and the more common type 2 (T2D) diabetes. Both T1D and T2D patients develop heart failure even in the absence of other cardiac risk factors, such as coronary artery disease, hypertension, and significant valvular disease. Nearly 80% of the deaths related to diabetes are attributed to cardiac complications. Although drugs and insulin have been successfully used to treat high blood glucose levels in diabetic patients. Despite maintaining adequate blood glucose levels in diabetic patients, the latter has not been enough to prevent cardiac complications. Plant-based dietary nutrients referred to as nutraceuticals have been the basis for innovative strategies to promote health and prevent or slow the progression of chronic diseases. The term nutraceutical is defined as a food or portion of food, that has a medical or health benefits, including the prevention and treatment of chronic disease. Citrus fruits such as oranges, mandarins, grapefruit are notably rich in flavonoids, and citrus flavonoids have been demonstrated to protect against diabetic complications. Among them, naringin found mainly in grapefruits and oranges has been reported to be helpful for the treatment of obesity, hypertension, cardiovascular diseases, and blood glucose levels in diabetic patients. However, no studies have been carried to determine if naringin, in addition to helping to maintain normal blood sugar levels, can protect diabetic patients from developing heart failure. In two experimental mouse models of diabetes, we have previously found that their heart cells have elevated intracellular calcium concentrations, elevated production of free radicals, a decrease in cell viability, reduced glucose transport into the cells, and low expression of ATP sensitive potassium channels. This project will explore whether or not naringin provides cardioprotection in diabetic models, and whether or not this protection is elicited via the expression of the ATP sensitive potassium channels. Our preliminary work suggests that naringin represents a novel therapeutic approach and an exciting and promising new direction for treating diabetic patients. We hope that this new therapy can eventually prevent or modify the progression of diabetic heart failure. 
• Nirat Beohar, MD, Principal Investigator & Steve Xydas, MD, Angelo LaPietra MD, George Gonzalez, MD, Co-Investigators, Mount Sinai Medical Center, research study entitled: "A Cerebral Embolic Protection during High-Risk Cardiac Surgery: A Feasibility study of the Sentinel Cerebral Embolic Filter Device to Reduce Neurologic Complications”. Stroke and cognitive dysfunction are related complications after cardiac surgery. Despite technical improvements the rates of stroke (as high as 4%) and neurocognitive decline (as high as 50-70%) after cardiac surgery have remained mostly unchanged over the years. The Sentinel CEP filter (Boston Scientific, Minneapolis, MN), remains the only currently FDA approved device indicated for reduction of clotting debris in trans-catheter aortic valve replacement (TAVR) procedures. There are currently no data studying the use of this device in cardiac surgery. The importance of reducing adverse neurological events after cardiac surgery and the indication from TAVR data that the CEP may be effective, suggest that a randomized trial of CEP with the Sentinel device should be done to guide future surgical therapy and Guidelines. Our proposed 30-patient feasibility study aims to: 1. Evaluate the practicality of placing and removing the CEP in the operating room using a mobile X-ray (C-arm); 2. Assess the ability to scientifically characterize debris collected in the CEP filter; 3. Determine the frequency of embolic debris collection in the CEP device; and to 4. Investigate the possibility of conducting pre-operative and post-operative (30 days after surgery) neurological evaluations. 
• Chunming Dong, MD, University of Miami, research study entitled: "The Use of CRISPR/CAS9 Technology to Prevent Acute and Chronic Rejection in Cardiac Allograft Transplantation". Clustered Regularly Interspaced Short Palindromic Repeats-Cas9 (CRISPR-Cas9) is a gene editing technique that has revolutionized genome engineering and allows for efficient gene knockdowns and knock-ins. Organ transplantation between species is known as xenotransplantation. With the advent of CRISPR-Cas9 technology, there is a rush for xenotransplantation using genetically modified pig organs in humans to tackle donor organ shortage. However, xenotransplantation as a clinical experimental treatment has had a very limited success. Furthermore, although xenograft transplantation may eventually lead to the clinical use of animal organs that will overcome the shortage of human organs, multiple hurdles remain before animal organs can be made available in routine medical care. These include ethical dilemmas, uncertain clinical outcomes, availability and cost of the genetically modified organs, insurance coverage, as well as policy issues. On the other hand, allograft organ transplantation (AOTx) using organs from the same species (i.e., human donors) has proven to be a life-saving approach for patients with end-stage heart, lung, liver and kidney diseases5. This isn’t to say that AOTx recipients do not face challenges. They are at increased risk for acute rejection (AR) and chronic rejection (CR) manifested as progressive cardiac allograft vasculopathy in heart transplant recipients. As a result, patients have to be on prolonged and heightened immunosuppression necessary to prevent AR, which increases their susceptibility to the development of cancers and infections. The common denominator for all of these morbidities is alloimmunity and the use of immunosuppressants. Therefore, approaches that could decrease the immune response to the graft without the need for prolonged and heightened immunosuppression would be of substantial therapeutic value.  With the strong and sustaining support from MHRI, Dr. Dong’s laboratory has made considerable progress in solving the root cause of allo-immunity—the holy grail of transplantation medicine. They mastered the CRISPR-Cas9 technology—an efficient and effective gene editing tool. They developed a novel dual sgRNA lentiviral vector (DSLV) containing sgRNAs for both MHC class I & II—molecules responsible for triggering immune response. Using this advanced CRISPR-Cas9 gene editing system, they have efficiently ablated MHC I and II in endothelial cells (ECs) and livers in mice. Upon implantation into the allogeneic recipient mice, the genetically modified ECs and livers showed markedly suppressed alloimmune reaction and improved survival, similar to unmodified allografts treated with immunosuppression. Recently, they have transitioned to applying CRISPR-Cas9 technology to ablate human leukocyte antigens (HLA—the MHC class I and II equivalent in humans). Traditional methods for delivery of CRISPR-Cas9 are based on the usage of lentiviral or adenoviral systems but those strategies have undesirable effects in humans reducing their potential clinical utility. They have developed a viral-free delivery strategy to deliver CRISPR-Cas9 systems safely and efficiently to human cells. They used this advanced delivery system to successfully knock out HLA Class I molecules (HLA-ABC) by targeting beta-2 microglobulin (β2M), which is a component of the HLA system required for surface expression of class I HLA molecules (e.g. HLA-ABC). They are in the process of designing sgRNAs for HLA-DR to further suppress rejection in human transplants, to reduce the need for high-level immunosuppression and, thus lessening the adverse consequences associated with immunosuppression. The success of this project will revolutionize the allograft transplant medicine with the goal of creating off-the-shelf universal donor hearts and other organs.
• Lina Shehadeh, PhD,  University of Miami, research study entitled: “Anti-Osteopontin Monoclonal Antibody Therapy in a Pig Model of Atherosclerosis”.  Atherosclerosis is a chronic inflammatory disease of the arteries responsible for up to 50% of all deaths in westernized society. It is principally lipid-driven, initiated by the accumulation of low-density lipoprotein (LDL) cholesterol. Clearance of LDL cholesterol from the bloodstream is therefore the first line of therapy and can be achieved by uptake via the LDL receptor (LDLR) in the liver. Existing therapies like statins and anti-PCSK9 antibodies are potent in LDL cholesterol clearance via increase of LDLR in the liver. In this project funded by the Miami Heart Research Institute, the Shehadeh lab will investigate how anti-Osteopontin (OPN) antibodies can further increase LDL cholesterol clearance. Data from the lab suggest that anti-OPN antibodies can further elevate LDLR levels and increase LDL cholesterol clearance. Experiments are proposed to develop the antibodies and validate findings in a large animal (pig) model of atherosclerosis. 
•  Jeffrey Goldberger, MD,  University of Miami, research study entitled: "Atrial ECG Assessment in Atrial Fibrillation". Atrial fibrillation (AF) is the most common heart rhythm disorder and current therapies for AF are suboptimal, particularly catheter ablation which is a procedure designed to eliminate AF by burning or freezing the areas in the heart responsible for the AF. The widely available electrocardiogram (ECG) records the electrical activity of the heart and is a "window" into the underlying heart problems. While physicians can easily recognize AF on the ECG, at this time the only information that is extracted from the ECG is whether the patient has AF or not. Because AF is a very rapid and disorganized rhythm in the upper chambers of the heart, it also appears to be a very rapid and irregular rhythm on the ECG. The electrical waves generated during AF are small and occur throughout the cardiac cycle. These waves are called fibrillatory waves. Although physicians recognize that these waves have multiple appearances, we do not have tools to differentiate one patients fibrillatory waves from another patient. This is unfortunate as the ECG is the most widely used tool for evaluation of patients with AF. This project uses advanced signal processing techniques to analyze the fibrillatory waves seen in the ECG in patients with AF and assess whether the fibrillatory wave characteristics can help physicians assess whether ablation will be effective.
  
• Florida Heart Research Foundation Cardiovascular Doctoral Student Grant Program at FIU: 
• Daniel Chaparro, PhD Candidate, Florida International University, research study entitled: "Valvular Heterogeneity in Bicuspid Aortic Valve Disease and Post Developmental Remodeling".  Bicuspid aortic valve (BAV) disease is the most common congenital defect in humans where a person is born with two instead of three leaflets within the aortic valve (AoV). People born with this defect are at a much higher risk of developing early onset aortic valve disease (AVD) necessitating valvular replacement intervention sooner and more frequently. While investigating a common genetically modified mouse model of BAV, we noticed a pattern between melanocytic pigmentation on the tissue and the presence of this congenital defect. Now, we are actively investigating if melanocytic pigment production itself plays a role in BAV malformations and AVD progression by using some genetically modified mouse models of varying pigmentation levels. 
• Perony Nogueira, PhD Candidate,  Florida International University, research study entitled: "Developmental origin of elastin producing cells and mechanism underlying elastogenesis in the murine aortic valve". Our group has recently demonstrated that the presence of pigment in the heart aortic valve is related to the arrangement of elastic fibers responsible for the mechanical behavior of the valve. My project aims to determine the origin and characteristics of the cells that make pigment in the valve. I have found that the pigment cells derive from at least two precursor populations. I have also found that in addition to the cells known to produce elastin in other tissues, namely fibroblasts and endothelial cells, pigment cells in the valve can make elastin.
  
• Abeer Al Barghouthi, PhD Candidate, Florida International University, research study entitled: “The Role of 3D Multiscale Biophysical Cues on the Maturation Advancement of Induced Pluripotent Stem Cell-Derived Cardiomyocytes”. Heart disease continues to exert a significant global burden, contributing to millions of fatalities every year. To date, there are no clinical solutions that regenerate tissue damaged by a heart attack. A promising avenue to address this dire need involves induced pluripotent stem cell-derived cardiomyocytes (iCMs), engineered heart cells with potential to repair the damaged tissue. However, iCMs in their current state do not fully resemble or behave like the native heart cells. They lack advanced structural organization and functional maturity. Native heart cells, cardiomyocytes (CMs) thrive in a complex 3D setting within the body, specifically the extracellular matrix (ECM). They interact with various biophysical cues from the surrounding environment at multiple scales. We seek to unravel the mechanisms by which these 3D-ECM inspired biophysical cues influence the development of iCMs. We will investigate the individual and collective roles of these cues on the maturation of iCMs at multiple length scales. This work will uncover some of the passive mechanical regulators of heart muscle maturation and enable us to use those mechanical cues in biomanufacturing mature engineered heart tissues. 
• Yih-Mei Lin, PhD Candidate,  Florida International University, research study entitled: "Development of Physiological Cardiac Patch for Diminishing Adverse Events of Ischemic Heart Injury”. Myocardial infarction (MI) continues to be a leading cause of morbidity and mortality worldwide. With the development of ischemic injury, the myocardium goes through a series of stages from acute inflammation, proliferation and repair, to scar tissue maturation and ventricular remodeling. These events not only cause the death of cardiomyocytes but also gradually break down the extracellular matrix and eventually form fibrotic scar tissue. Without proper treatment, this will result in the obstruction of blood flow and dysfunction of heart. One of the current cardiovascular approaches to treat MI is developing functional induced pluripotent stem cells differentiated cardiomyocytes (iPSC-CMs) derived cardiac patch; however, it has been challenging to overcome clinical requirement such as immune response. An enhanced engineered cardiac patch with improved functionality and immunosuppression property would be an urgent need to delay or reduce myocardial scar burden. The use of mechanical stimulation is in attempt to recapitulate the mechanical environment in the heart that is necessary for proper cardiac development. In fact, physiologically-oscillatory flow conditioning has been observed to facilitate de novo tissue deposition. In addition, mechanical stimulation has the potential to produce optimum cardioprotective cargo of exosomes. However, oscillatory flow stimulation has not related to the formation of cardiac tissue patch and the effects of exosomes released from iPSC-CMs on the patch remain unclear. Therefore, this study aims to address the role of physiologically-oscillatory flow in facilitating iPSC-CMs derived cardiac patch development and the potential application of iPSC-CMs-derived exosomes to the patch. The efforts of this study could offer a new strategy to enhance the production of cardiac patch with functional recovery property and minimal translational challenges.
• Manuel Perez-Nevarez, PhD Candidate,  Florida International University, research study entitled: "Flow-Induced Conditioning of Stem Cells for the Production of Cardioprotective Exosomes”. Stem cell therapy has previously been investigated as an option for the treatment of infarcted cardiac tissues. However, recent findings suggest that the beneficial effects of stem cells are the localized secretion of bioactive factors that act to recapitulate the therapeutic effects of the parent stem cells. A subset of these secreted factors (exosomes) contain growth factors and proteins, that may potentially be used as therapeutic agents to promote the healing of injured heart tissue. Mesenchymal stem cells (MSC) are able to respond and adapt to forces sensed from their external microenvironment. It has been shown that physical cues produced by fluid-induced shear forces significantly modulate MSC function and increase the production of both proteins and secreted exosomes. In addition, pulsatile flow regimens have been shown to induce preferential MSC gene expression and phenotype. However, the relationship between the specific flow parameters of the conditioning regimen and the production of cardioprotective exosomes is not fully understood. There is a need for the development of a process that can produce exosomes with optimal secretory contents for use in cardiac applications. The proposed study will provide insights on the flow-conditioning parameters that upregulate the production of cardioprotective exosomes as well as their effects on in-vitro models of cardiac ischemia. Determination of an efficacious preconditioning regimen could lead to the identification of a drug delivery strategy for cardiac wound healing applications.

2022-2023 NEW & CONTINUED RESEARCH RECIPIENTS/PROJECTS:

• LaPrincess Brewer, MD , Mayo Clinic Rochester, research, education and prevention grant for "FAITH! Emergency Preparedness Initiative: First Aid CPR and AED Training Among African-American Churches":  The recent cardiac events of Damar Hamlin and Bronny James highlighted in the media shine a spotlight on a vital issue: the importance of cardiopulmonary resuscitation (CPR) training and readily available automated external defibrillators (AEDs). Thanks to both, and the quick actions of bystanders, these young men are on their way to recovery. Their survival stories are event more compelling considering the significant survival disparities for African-Americans in out-of-hospital cardiac arrest situations. The New England Journal of Medicine recently published a study which found that despite the significantly increased chances of survival with immediate CPR, Black and Hispanic individuals receive these life-saving efforts from bystanders far less often than their White counterparts. This was true not only in predominantly White neighborhoods, but also in public locations and predominantly Black or Hispanic neighborhoods. These findings demonstrate the critical need for CPR training and access to AEDs in these disproportionately impacted communities.  The FAITH! (Fostering African-American Improvement in Total Health!) Program, led by Mayo Clinic cardiologist, Dr. LaPrincess Brewer, partners with local African-American churches to increase awareness and prevention of cardiovascular disease (DVD) through multi-component healthy lifestyle interventions. The program's primary goal is to promote health and wellness in a culturally relevant, faith-based manner to address ongoing health disparities in African-Americans. Given the staggering disparities related to bystander CPR and cardiac arrest survival, along with the disproportionate incidence of cardiovascular risk factors in African-Americans, we aim to increase knowledge and preparedness to handle life-threatening CVD emergencies by offering CPR training and equipping partnering churches with on-site AEDs.
• LaPrincess Brewer, MD,  Mayo Clinic Rochester, research, education and prevention grant for "FAITH! Hypertension App Mobile Health Initiative to Improve Hypertension Control and Cardiovascular Health Among African-Americans":  The FAITH! (Fostering African American Improvement in Total Health!) Program, led by Mayo Clinic cardiologist, Dr. LaPrincess Brewer, has previously leveraged community-academic partnerships in Minnesota to co-design a smartphone-based mobile app (FAITH! HTN App) with patients and clinicians to promote hypertension self-management with culturally tailored resources. The app was integrated into a 2021 pilot collaboration with a federally qualified health center (FQHC) In Minneapolis, MN to support a Centers for Disease Control and Prevention (CDC) initiative for cardiovascular disease prevention/management in disproportionately impacted communities. This project involves an integrated care model (ICM) and the mobile health intervention to improve hypertension self-management in under resourced, high-risk African-American patients while simultaneously addressing adverse social determinants of health (SDOH). The app provides culturally relevant education tools to promote patient self-empowerment for hypertension control.  The ICM includes weekly check-ins between patients and Community Health Workers (CHWs) to assess blood pressure control and screen for SDOH acting as barriers to care. Patients are referred to community resources for unmet needs. The CHW reports and app allow for meaningful clinical data transfer to enhance the patient-clinician relationship and hypertension care plans. The successful 2021 pilot study resulted in improved blood pressure among African-American patients with uncontrolled hypertension. There was a clinically meaningful 6-point reduction in systolic BP, from baseline to immediate post-intervention (N=7). Additionally, the FAITH! HTN App increased participant knowledge of cardiovascular topics including HTN, as there were statistically significant increases in self-assessment quiz scores on education modules. Positive behavioral changes related to HTN self-care were also observed. In follow-up focus groups and surveys, patients notes that the intervention fostered healthy lifestyle changes and overall accountability for hypertension self-management including and beyond medication adherence. Patients perceived the FAITH! HTN App as engaging, informative, and found the peer support through the sharing board particularly useful. We are currently moving forward with a larger-scale trial in collaboration with another FQHC, Neighborhood Health Source, which will include 100 total participants randomized to either an intervention group (using the app) or control group (standard of care). 
• Nanette Bishopric, MD, Georgetown University, research study entitled: “Restoration of Heart Function by Targeting Remodeling Pathways in the Ischemic and Stressed Heart”.   The heart is very resilient, and heart muscle cells (the cell type that beats) are very long-lived. Over a lifetime of continuous beating, they adapt dynamically to changes in body size, hormonal state, and activity, and successfully meet a variety of acute challenges, ranging from febrile illnesses to tennis matches to marathons. However, certain common chronic diseases, such as high blood pressure and diabetes, cause persistent and ongoing stress that can lead to damaged function and heart failure. Despite recent success in treatment and prevention of heart attacks, cardiovascular disease continues to be the #1 cause of death in the US, as it has been since the middle of the last century. The reason is the increasing frequency of heart failure – particularly the kind known as Heart Failure with Preserved Ejection Fraction (HFpEF). More than 3 million people in the United States are living with this kind of heart failure. Heart attacks weaken the ability of the heart to pump. In contrast, HFpEF prevents the heart from relaxing. This means that it takes higher pressure to fill it with blood for the next beat. The abnormal pressure is felt in all the filling systems of the heart, especially the lungs. This in turn leads to shortness of breath, reduced exercise capacity, and a high risk of atrial fibrillation. Recognized only recently as a disorder, the incidence of HFpEF is increasing rapidaly along with its major known causes: obesity, physical inactivity, diabetes, high blood pressure, and old age. There is no known cure and no specific treatment for HFpEF, although symptoms can be relieved with daily medication. Groundbreaking research in our laboratory, along with others, has now begun to shine light on exactly what goes wrong at the molecular and cellular level in HFpEF, leading the way to more effective targeting and reversal of this debilitating and eventually fatal condition. In this ongoing project, we are working to understand the causal relationship between chronic stress and HFpEF. Our working hypothesis is that certain kinds of chronic diseases (e.g. diabetes, hypertension, and obesity) trigger a maladaptive molecular response involving that impairs the ability of the heart muscle to relax. With the multi-year support of the Miami Heart Research Institute, we have been able reveal a network of biochemical pathways in the stressed heart cell that lead to HFpEF. We have designed and tested novel structurally-designed molecules that have shown promise in reversing HFpEF by acting on processes within the heart muscle itself. Our aim in the current year of funding is to continue these efforts, but also to look at novel stress factors common to inflammation, cancer chemotherapy and aging, to see how these factors adversely impact the heart’s genetic response pathways. In Aim 1, we will explore the role of RAGE, a cell surface receptor that mediates some of the harmful effects of diabetes and aging, as an indirect source of damage to the heart. In Aim 2, we will use the cancer chemotherapy agent doxorubicin (Adriamycin) to model the effects of acute oxidative stress on the heart. These new models will help us to understand how to combat the stress signals that lead to heart damage, and ultimately to prevent HFpEF-related morbidity and mortality, as well as to reverse it.
• Joshua Hutcheson, PhD & Alexander Agoulnik, PhD, Florida International University, research study entitled: "A Novel Small Molecule Therapy for Late-Stage Atherosclerosis". Despite great progress in understanding the factors that contribute to heart disease and the development of effective cholesterol-lowering medications like statins, heart disease remains the leading cause of death worldwide. One major culprit in heart disease is the buildup of plaques in our arteries. These plaques form when arteries become inflamed and accumulate fatty substances like cholesterol. Atherosclerosis occurs when these plaques cause the vessels to narrow. If the vessels within the heart become too narrow, blood flow is restricted, and the heart muscle does not receive adequate oxygen needed for function. If the plaques rupture, blood flow can immediately stop, causing major heart attacks that lead to sudden death.  Current guidelines recommend strategies like taking cholesterol-lowering drugs and making lifestyle changes like losing weight and quitting smoking to reduce our risk of heart disease. These strategies have immediate benefits but can often take years for a person’s risk to return to a normal baseline. This lingering risk is likely due to plaques that do not go away completely, even with medication and lifestyle changes. These methods mainly help prevent new plaques from forming or getting worse, but they do not quickly get rid of the ones that are already present. Recently, studies have sought to reduce this lingering risk by targeting the inflammation that contributes to plaque formation. Strategies have included a treatment that uses antibodies to lower inflammation in the body. The results from clinical trials have been promising, with fewer heart problems in people who received this treatment. However, there are some downsides to this approach, like the need for frequent antibody injections. In our study, we want to see if a more appropriate kind of medication, a small molecule, can help reverse these plaques when combined with statins and lifestyle changes. This small molecule targets a specific receptor in the body that has been shown to be safe in large clinical trials. So far, our data shows that this molecule can prevent and even reverse a late-stage complication of plaque build-up called vascular calcification. Interestingly, just making lifestyle changes doesn't seem to have the same effect on this late-stage complication. The small molecule used in our study may be able to reprogram the cells involved in inflammation such that they help clear away existing plaque. Our ongoing research in the current year of funding seeks to further explore how to reverse existing plaque and to identify which compounds are the most effective in concert with lifestyle and cholesterol-lowering treatments. The long-term goal is to develop a treatment that people can take to reverse plaques and reduce their risk of heart problems.
• Joshua Hutcheson, PhD (Principal Investigator) & Prem Chapagain, PhD, Jin He, PhD & Francisco Fernandez-Lima, PhD (Co-Investigators),  Florida International University, research study entitled: "A Nanoanalytical Approach to Unraveling Differences Between Physiological and Pathological Mineralization".   Calcification, the deposition of calcium mineral, occurs prominently in two tissues: physiological bone formation and in the diseased artery wall. Vascular calcification in the arteries is the most significant predictor of future cardiovascular disease and mortality. Bone-like mineral formation can cause plaque rupture, leading to sudden heart attacks and strokes, and stiffens blood vessels, increasing stress on the heart. Interestingly, the amount of mineral in bone and vascular tissues tend to inversely correlate—a phenomenon known as the “calcification paradox.” Increased vascular calcification is observed in patients with lower bone mineral density. Development of treatments that can restore appropriate mineral balance is hindered by an incomplete understanding of the mineral formation process in each tissue. Though many bone-like mechanisms are observed during vascular calcification, our data indicate that fundamental differences in the calcification processes of bone and vascular cells may underlie the calcification paradox. This interdisciplinary study will use novel material characterization and molecular biology approaches to analyze the earliest possible mechanisms in mineralization and provide new insight into the fundamental differences between bone and vascular calcification.
• Sharan Ramaswamy, PhD, Florida International University, research entitled "Additional In Vitro Assessments of Decellularized and Dehydrated Augmented Elastin Heart Valve to Confirm its Functionality, Durability and Cellular Responses".  Heart valve replacements with the capacity to regenerate are conceptually very appealing in the treatment of critical valve diseases in the young, because of their potential to grow with the child. Our studies to-date with support from the Florida Heart Research Foundation have successfully enabled the deposition of allogeneic, elastin in the extracellular matrix (ECM) by stem cells which are subsequently decellularized but retaining the elastin content. This valve-relevant elastin is known to trigger cellular chemotaxis, which would thereby facilitate accelerated valve regeneration after implantation. However, prior to further in vivo assessment, our immediate goals are first to perform the following in vitro testing: (i) confirm the augmented elastin valve’s ability to hydrodynamically function well in the acute term in the mitral valve location using a pulse duplicator system and confirm its durability for an equivalent of 3 months using a valve durability tester, which is the time frame in which we anticipate full valve regeneration, based on our existing results, (ii) assess the ability of valvular cells to be able to secrete ECM on the augmented elastin valve after 2 weeks of culture, (iii) perform a preliminary examination of the immune response, via 2 weeks of co-culture of immune cells with valvular cells on the augmented elastin valve. Our previous findings have demonstrated that a raw bio-scaffold remains relatively undegraded up to 3-months post-implantation, in the mitral valve location in a juvenile non-human primate model. Thus, confirmation of an acceptable hydrodynamic functionality and 3 months-equivalent durability of the augmented elastin valve, as well as a favorable response by valvular cells and immune cells to the augmented elastin valve, will thereby establish that it can permit full valve regeneration in vivo. Completion of these project goals will subsequently permit us to assess if the fully decellularized, augmented elastin valve can support somatic growth. In summary, these three project goals are major steps towards our translation efforts to in vivo assessment and subsequent clinical trials, where currently, critical congenital valve diseases in young children have a very poor prognosis for survival. To quote Dr. Ramaswamy, "I consider it my life's mission to be able to effectively resolve critical congenital heart valve defects in children who are born with this dreadful condition, for which there is no current treatment option."
• Florida Heart Research Foundation Cardiovascular Doctoral Student Grant Program at FIU: 
• Daniel Chaparro, PhD Candidate, Florida International University, research study entitled: "Aortic Valve Leaflet Innervation in Tissue Mechanics and Disease Progression".  Surprisingly, there are neurons within the aortic valve. However, their role in aortic valve function and disease remain unknown. The aortic valve ensures that blood flows in one direction from the heart to the rest of the body. A well-defined structure gives the aortic valve the unique mechanical properties required to open and close as the heart beats. Disruption of this structure during aortic valve disease (AVD) leads to heart failure. The tissue, specifically the aortic valve leaflets (AVLs), is maintained by a complex mixture of cells. Currently there is no treatment for AVD and to develop new therapeutic options we first need to understand how neurons, and other cells, within the tissue work to maintain aortic valve structure and function. Neurons reside on the side of the AVL that experiences the most mechanical stress during the cardiac cycle. AVL neurons decrease in abundance with age at a rate that mirrors the onset of AVD in human patients. These cells also associate with formation of the AVL structure during development in our experimental models. We hypothesize that AVL neurons can sense the mechanical environment within AVLs and play a role in controlling valve mechanics and that neural dysfunction leads to AVD progression. In this project we explore the role of aortic valve neurons in function and disease. The outcomes of these studies could lead to new therapeutic targets for AVD, a major cause of heart disease. 
• Perony Nogueira, PhD Candidate, Florida International University, research study entitled: "Developmental origin of elastin producing cells and mechanism underlying elastogenesis in the murine aortic valve".  In the United States alone, there were more than 27,000 deaths related to valvular heart disease in 2017 according to the CDC and these numbers are increasing over time. The aortic valve plays an important role in heart physiology by preventing the backflow of blood from the body to the left ventricle of the heart. One of the important components of the aortic valve that ensures its proper function is elastin. We have recently shown that the cells that produce elastin in the aortic valve share characteristics with pigment cells, melanocytes, and smooth muscle cells. We have also found that aortic valves that have no pigment are almost completely devoid of elastin fibers. The main goal of this study is to determine the developmental origin of the elastin producing cells and how pigment synthesis is associated with the process of elastin production in the aortic valve. We will use genetically modified mice to establish if the precursor population that gives rise to melanocytes in the skin is also responsible for the generation of the elastin producing cells in the aortic valve. We will immune label elastin and perform electron microscopy to investigate how its production and secretion is affected in the aortic valve of hypopigmented mice. Finally, we will attempt to rescue the lack of elastin fibers in the aortic valve of these mice by bypassing the need for the rate limiting enzyme in pigment production. This study will contribute to a better understanding of AoV development and elastin related pathology affording us with potential novel approaches for treating valvular disease.
• Mohammad Shaver, PhD Candidate,  Florida International University, research study entitled: "The Role of Mechanical Stimulation in the Biogenesis of Vascular Calcifying Extracellular Vesicles". Heart disease is a leading cause of death in developed countries, especially in the United States. One of the main indicators of high risk for heart disease is the presence of vascular calcification, which occurs when bone-like minerals form in the walls of arteries. This calcification process often starts when small particles called calcifying extracellular vesicles (EVs) are released from vascular smooth muscle cells (VSMCs) in response to abnormal conditions. The formation of calcifying EVs requires a specific protein called caveolin-1 (CAV1). This protein is located in the membrane of VSMCs and helps sense and respond to changes in the mechanical environment within the tissue. Hypertension is a leading risk factor for the development of heart disease in general and calcification in particular. However, the effects of mechanical stimulation and the formation and release of calcifying EVs from VSMCs is not yet fully understood. Therefore, the aim of this research study is to investigate how mechanical stretch affects the movement of CAV1 within VSMCs and the associated formation and calcification of EVs. By examining the impact of the mechanical environment on EV formation and calcification, this study hopes to uncover new insights into the role of factors that cause vascular calcification. The outcomes of this study could potentially lead to the discovery of therapeutic approaches to regulate the trafficking of CAV1 and treat vascular calcification more effectively.
• Jose A Adams, MD, Mount Sinai Medical Center, research study entitled: "Whole Body Periodic Acceleration (pGz) in Heart Failure".  Heart failure (HF) is a devastating problem which occurs in more than 50 per 1000 individuals greater than 65 years of age. The lifetime risk of heart failure from ages 45 through 95 years is 20-45%. The symptoms of HF are varied but include; shortness of breath, easy fatigue, intolerance to exercise, fluid retention, and congestion of the lungs. The causes of HF include; scarring of the heart due to previous heart attack, uncontrolled diabetes and hypertension, genetics and other still unknown causes. Death from HF remains at approximately 50% within 5 years of diagnosis. Additionally, HF accounts for over 1 million hospitalizations annually. Furthermore, the total cost of HF in the US exceeds $30 billion annually, making HF a significant public health problem and economic burden. Whole Body Periodic Acceleration (pGz) is the back and forth motion of the body in a head to foot direction utilizing a bed like platform. The motion is similar to “a mother pushing a baby carriage back and forth”. The pGz motion induces pulsations to the body in the in all blood vessels, liberating beneficial substances from the cells which line these vessels. Previous grant support from the Miami Heart Research Institute/Florida Heart Research Foundation have allowed our laboratory to show that pGz improves the function of the heart after cardiac arrest. Additionally, pGz performed before (pre-conditioning) cardiac arrest or a heart attack, improved recovery, and heart function when compared with no treatment. This project investigates the use of pGz in models of the most common causes of HF. The study will determine whether or not pGz will improve heart function after established HF and will seek to determine if such improvements in heart function are related to the effects of pGz on heart scarring, excess inflammation, and other biochemical pathways. The findings of this study when applied to populations with HF could have a tremendous impact in reducing death, improving quality of life, and reducing healthcare costs in those affected by HF. 
• Gervasio A. Lamas, MD/Christos Mihos, DO, Mount Sinai Medical Center, research study entitled: “Effects of Exercise and FITness on Left Ventricular Torsion and Wall MechanIcs STudy (FIT-TWIST)”.  Exercise capacity is one of the most important markers of cardiovascular health. Cardiac ultrasound imaging (i.e. “Echocardiography”) is the primary method used by cardiologists to evaluate heart function. Yet for many years, cardiologists could not, by looking at an echo, tell whether the patient was fit, or a “couch potato”. The standard metric to express cardiac function, the ejection fraction (EF), or the percentage of blood ejected with each heartbeat (normal is 55% to 65%), simply does not reflect exercise capacity. Evidence suggests that the cardiovascular benefits of fitness are strongly influenced by the health of cardiac mechanics, which are measured using an advanced echocardiographic technique called 2D speckle-tracking echocardiography. This method has the capability of quantifying subtle aspects of cardiac motion and “fitness” based on the way the heart moves – shortening and twisting when it contracts, or “pumps”, and reversing its motion to relax. This study of cardiac mechanics in health and ischemic heart disease, will enroll 150 healthy subjects and assess the effects of different forms of exercise on cardiac mechanics in FIT-TWIST/Health. We hypothesize that the cardiac mechanics of normal subjects will change in a favorable way and guide ultimate selection of the most beneficial form of cardiovascular exercise. In FIT-TWIST/MI, we will assess 50 patients who have had a “heart attack” (myocardial infarction, MI), an insult to cardiac structure that leads to major disruption of cardiac mechanics. In these patients, we will study the effects of a standard cardiac rehabilitation program, a program of 36 sessions of graded exercise over a 12-week period. We hypothesize that cardiac rehabilitation restores some degree of normality to cardiac mechanics, thus explaining the extreme benefit on post-MI survival of cardiac rehab participation.
• Gervasio A. Lamas, MD, Mount Sinai Medical Center, research study entitled: "Trial to Assess Chelation Therapy 3a (TACT3a)".  Diabetes triples the risk for fatty deposits in arteries, including in the heart, brain, and legs. We will use the most severe manifestation of arterial blockages, critical limb-threatening leg and foot artery blockage, as a marker of extreme risk for patients with diabetes. TACT3A will test a novel therapy, chelation, to try and reduce risk in these very ill patients. Chelation is a process by which a medication “sticks” to various toxins in the blood, usually toxic metals, like lead and cadmium, acquired from the environment, and allows them to be harmlessly excreted. Edetate disodium is a repurposed old drug, a chelator with high affinity for lead and cadmium, 2 common toxic metals that are toxic to coronary and other arteries. We will enroll 50 patients at Mount Sinai with diabetes and severe blockages of the leg arteries and try to prevent major amputation, coronary revasculari-zation, stroke, MI, or death (all-cause) during an average 1.25 years of follow-up. Patients will be randomly assigned to chelation or placebo. Treatment will consist of 40 active or placebo infusions over 30 weeks. This study, if successful, will be presented to FDA as part of the rapidly growing evidence that environmentally acquired metal pollutants are a reversible risk factor for cardiovascular disease and that chelation is a safe and effective therapeutic intervention in patients with extremely high risk of cardiovascular events. 
• Demilade Adedinsewo, MD,  Mayo Clinic Jacksonville, research study entitled: "Evaluating ElectroCardioGram based Artificial Intelligence predictions across device types (ECG-AI)".  Utilizing artificial intelligence to analyze the 12-lead electrocardiogram (ECG), a first line diagnostic test for detection of heart disease, has enhanced the ECGs ability to accurately predict multiple cardiac disorders. The use of artificial intelligence in this context currently exceeds human-level interpretation of the ECG test. Despite its remarkable performance, there are significant challenges with scaling this technology and making it accessible to all for cardiovascular care. This is often due to differences in ECG data configuration, formats, and storage practices across health care institutions within the United States. The overall goal of this study is to develop and establish a process for extraction and integration of digital ECG signals from multiple devices, thus making novel artificial intelligence algorithms more accessible so patients can benefit equitably from this technology, facilitate data sharing/transfer, and support dataset curation for development of newer prediction algorithms.
• Brian Shapiro, MD/Bryan Taylor, PhD , Mayo Clinic Jacksonville, research study entitled: “Exercise Training to Improve Pulmonary Haemodynamic and Right Ventricular Function in Heart Failure Patients with Pulmonary Hypertension”.  A common and very dangerous consequence of heart failure is disease of the blood vessels that supply the lungs, which results in a large increase in lung blood pressure; this is known as pulmonary hypertension. Pulmonary hypertension is actually a group of conditions. It may be caused by disease of the lung arteries themselves (“Group 1”), occur due to heart disease (“Group 2”) or lung disease (“Group 3”), or as a consequence of previous blockage of the lung blood vessels (“Group 4”). However, heart failure is one of the leading causes of pulmonary hypertension worldwide. Compared to heart failure patients without pulmonary hypertension, those with pulmonary hypertension have worse symptoms, are more limited in their ability to exercise and perform routine daily tasks, have to be hospitalized more regularly, suffer greater heart damage, are more likely to need a heart transplant, and are at a much greater risk of premature death. Worryingly, drugs typically used to treat pulmonary hypertension do not typically work, and may even worsen symptoms, in heart failure patients. As such, there is a real and urgent medical need to identify alternative safe and effect treatments for pulmonary hypertension due to heart failure. We know that improved physical activity through exercise training benefits patients with heart disease. There is clear evidence that moderate intensity exercise (e.g., brisk walking) can improve heart, blood vessel, and muscle function as well as overall health and well-being in heart failure patients. Preliminary work from our laboratory suggests that such exercise training is safe in heart failure patients with pulmonary hypertension. However, whether exercise therapy improves short-term clinical outcomes and overall physiological function in heart failure patients with pulmonary hypertension has yet to be addressed. The main aim of this project is to examine the safety and impact of supervised exercise training on short-term clinical outcomes (including disease severity and health-related quality-of-life), exercise capacity, and heart and lung blood vessel function in heart failure patients with pulmonary hypertension. Completion of this project will provide a critical first-step towards understanding the potential clinical and therapeutic benefit of exercise training in heart failure patients with pulmonary hypertension. Overall, our findings will have the potential to positively influence the therapeutic options available for the treatment of heart failure patients with pulmonary hypertension, and may help drive the acceptance of exercise training delivered by local, generic heart and lung rehabilitation services as a standard of care for patients with any form of pulmonary hypertension.   
• Joerg Herrmann, MD, Mayo Clinic Rochester, research study entitled: "TACTIC - TrAstuzumab Cardiomyopathy Therapeutic Intervention with Carvedilol Trial".  Breast cancer patients undergoing trastuzumab treatment are at risk of heart function decline or heart failure symptoms, but it is unknown if, when, and for how long cardiovascular protective strategies, e.g. with a beta-blocker, could help. This study randomly assigns those taking curative-intent trastuzumab to the beta-blocker carvedilol—either when significant heart function decline or subtle early signs of heart injury (either by elevation of a cardiac blood biomarker, i.e. cardiac troponin, or by an abnormal heart ultrasound marker, i.e. global longitudinal strain) are noted, or preventatively before beginning trastuzumab therapy. This study will further randomly assign those patients on carvedilol in these three groups to either discontinue at the end of trastuzumab therapy or to continue for another year, providing much needed clinical trial data on what the best strategy (“tactic”) for those at risk of cardiotoxicity with trastuzumab therapy is.
• Joerg Herrmann, MD, Mayo Clinic Rochester, research study entitled: “CAncer Survivor CArdiomyopathy DEtection (CASCADE)”.   Currently, there are over 15 million cancer survivors in the United States, and this number is projected to exceed 20 million within the next five years-- most of whom will be long-term survivors (5+ years). Many of these individuals are at a high lifetime risk of developing heart disease due to their exposure to anthracycline-based chemotherapy during cancer treatment. The most efficient and cost-effective way to monitor, predict and prevent the development of heart failure in these cancer survivors is not known. While echocardiography has been the standard approach, serial studies are costly and require logistics, time and effort, kindling interest in identifying less expensive cardiac surveillance strategies that can be implemented over long periods of time to a large population at risk. The current application’s objective is to assess and optimize the diagnostic performance of novel artificial intelligence (AI) electrocardiography (ECG) and an established blood marker for heart disease (NT-pro-BNP) for the detection of an abnormal heart function in cancer survivors and to compare and combine these two tests to define the most optimal strategy. These studies will inform cardiac surveillance efforts for clinical practice and the planning of a randomized clinical trial to address the clinical impact of optimal cardiac surveillance. 
• Claudia Rodrigues, PhD,  Florida Atlantic University, research study entitled: "Molecular Mechanisms of Anthracycline-Induced Cardiovascular Toxicity". Cardiovascular disease is the most common complication that develops in pediatric patients receiving chemotherapy. The survival rate of children who receive cancer treatment has significantly increased throughout the years. However, survivors are at high risk of suffering from different types of chronic health conditions due to chemotherapy toxicity, including cardiovascular disease. Heart injury, after exposure to chemotherapy agents, follows a progressive course in a significant number of patients, leading to congestive heart failure at a young age. The Rodrigues laboratory is investigating mechanisms underlying the cardiovascular toxicity of anthracyclines, a group of chemotherapy drugs used in the treatment of different types of pediatric and adult cancers. The goal of these studies is to identify novel mechanisms that can be therapeutically targeted for prevention of heart injury and preservation of cardiac function. This proposal specifically focuses on the identification of signaling mechanisms released from our blood vessels that impact the function of the heart under normal and chemotherapy exposure conditions. Since their discovery over 50 years ago, the toxic effects of anthracyclines to the cardiovascular system remain a significant medical problem. This project is an important step toward the identification of novel protective strategies that could be used to prevent chemotherapy-induced cardiovascular disease.
• Lina Shehadeh, PhD, University of Miami, research study entitled: “Anti-Osteopontin Monoclonal Antibody Therapy in a Pig Model of Atherosclerosis”.  Atherosclerosis is a chronic inflammatory disease of the arteries responsible for up to 50% of all deaths in westernized society. It is principally lipid-driven, initiated by the accumulation of low-density lipoprotein (LDL) cholesterol. Clearance of LDL cholesterol from the bloodstream is therefore the first line of therapy and can be achieved by uptake via the LDL receptor (LDLR) in the liver. Existing therapies like statins and anti-PCSK9 antibodies are potent in LDL cholesterol clearance via increase of LDLR in the liver. In this project funded by the Miami Heart Research Institute, the Shehadeh lab will investigate how anti-Osteopontin (OPN) antibodies can further increase LDL cholesterol clearance. Data from the lab suggest that anti-OPN antibodies can further elevate LDLR levels and increase LDL cholesterol clearance. Experiments are proposed to develop the antibodies and validate findings in a large animal (pig) model of atherosclerosis. 
• Chunming Dong, MD, University of Miami, research study entitled: "The Use of CRISPR/CAS9 Technology to Prevent Acute and Chronic Rejection in Cardiac Allograft Transplantation".  Clustered Regularly Interspaced Short Palindromic Repeats-Cas9 (CRISPR-Cas9) is a gene editing technique that has revolutionized genome engineering and allows for efficient gene knockdowns and knock-ins. Organ transplantation between species is known as xenotransplantation. With the advent of CRISPR-Cas9 technology, there is a rush for xenotransplantation using genetically modified pig organs in humans to tackle donor organ shortage. However, the first and only cardiac xenograft transplant recipient only survived for two months. The two gene-edited pig kidneys were transplanted into brain-dead humans with no apparent signs of kidney functions. Thus, although xenograft transplantation may eventually lead to the clinical use of animal organs that will overcome the shortage of human organs, multiple hurdles remain before animal organs can be made available in routine medical care. These include ethical dilemmas, uncertain clinical outcomes, availability and cost of the genetically modified organs, insurance coverage, as well as policy issues. On the other hand, allograft organ transplantation (AOTx) using organs from the same species (i.e., human donors) has proven to be a life-saving approach for patients with end-stage heart, lung, liver and kidney diseases5. This isn’t to say that AOTx recipients do not face challenges. They are at increased risk for acute rejection (AR) and chronic rejection (CR) manifested as progressive cardiac allograft vasculopathy in heart transplant recipients. As a result, patients have to be on prolonged and heightened immunosuppression necessary to prevent AR, which increases their susceptibility to the development of cancers and infections. The common denominator for all of these morbidities is alloimmunity and the use of immunosuppressants. Therefore, approaches that could decrease the immune response to the graft without the need for prolonged and heightened immunosuppression would be of substantial therapeutic value.  Dr. Dong’s laboratory not only has mastered the CRISPR-Cas9 technology, but has designed a proprietary sgRNA to guide the CRISPR-Cas9 system to ablate the major molecule responsible for triggering alloimmune response, namely the major histocompatibility complex (MHC) class I. Furthermore, they have developed a novel dual sgRNA lentiviral vector (DSLV) containing sgRNAs for both MHC class I & II (MHC II is another molecule triggering alloimmune response). Using this advanced CRISPR-Cas9 gene editing system, they have efficiently ablated MHC I and II in endothelial cells (ECs) and livers (easier to transduce than the heart and used for proof-of-concept). Upon implantation into the allogeneic recipient mice, the genetically modified ECs and livers showed markedly suppressed alloimmune reaction and improved survival, similar to unmodified allografts treated with immunosuppression. Based on these solid and exciting data, we propose to study the effects of MHC silencing in acute and chronic rejection using ECs, smooth muscle cells and aortic transplants—an established model to mimic heart transplantation to study AR and cardiac allograft vasculopathy (a major limiting factor for the long-term survival of cardiac transplant patients). Our project also has the potential to develop the technology that will lead to the production of universal donor tissues/hearts that will not activate the immune system as vigorously through targeted ablation of MHC in the allograft hearts. It will reduce the need for high-level immunosuppression and, thus lessening the adverse consequences associated with immunosuppression. The Miami Transplant Institute is the largest transplant center in the nation. With the success of this project, we will be well positioned to test our strategy in unused human hearts to evaluate the feasibility in humans. This will revolutionize the allograft transplant medicine with the goal of creating off-the-shelf universal donor hearts and other organs.

2021-2022 RESEARCH RECIPIENTS/PROJECTS: 

• Demilade Adedinsewo, MD, Mayo Clinic Jacksonville,  research study entitled: "Screening for PEripartum Cardiomyopathies using Artificial Intelligence (SPEC-AI)".    
• Jose R. Lopez, MD, Mount Sinai Medical Center,  research study entitled: “Cardioprotection in Diabetic Cardiomyopathy via upregulation of ATP-sensitive K+ channels”.    
• Nanette Bishopric, MD, Georgetown University,  research study entitled: “Restoration of Heart Function by Targeting Remodeling Pathways in the Ischemic and Stressed Heart”.   
• Sharan Ramaswamy, PhD, Florida International University,  research entitled: "Stem Cell-seeded bioscaffolds supporting somatic growth, function and remodeling in the treatment of critical congenital valve disease in the young".  
• Florida Heart Doctoral Student, Daniel Chaparro, PhD Candidate, Florida International University,  research study entitled: "Aortic Valve Leaflet Innervation in Tissue Mechanics and Disease Progression".
  
• Joshua Hutcheson, PhD & Alexander Agoulnik, PhD, Florida International University,  research study entitled: "A Novel Small Molecule Therapy for Late-Stage Atherosclerosis".   
• Jose A Adams, MD, Mount Sinai Medical Center,  research study entitled: "Whole Body Periodic Acceleration (pGz) in Heart Failure".
• Claudia Rodrigues, PhD,  Florida Atlantic University, research study entitled: "Molecular Mechanisms of Anthracycline-Induced Cardiovascular Toxicity".    
• Demilade Adedinsewo, MD, Mayo Clinic Jacksonville,  research study entitled: "Screening for PEripartum Cardiomyopathies using Artificial Intelligence (SPEC-AI)".  
  
• Lina Shehadeh, PhD, University of Miami,  research study entitled: “Anti-Osteopontin Monoclonal Antibody Therapy in a Pig Model of Atherosclerosis”.  
• Gervasio A. Lamas, MD/Christos Mihos, DO, Mount Sinai Medical Center,  research study entitled: “Effects of Exercise and FITness on Left Ventricular Torsion and Wall MechanIcs STudy (FIT-TWIST)”.      
  

2020 SUPPLEMENTAL RESEARCH RECIPIENTS/PROJECTS: 

• Joerg Herrmann, MD, Mayo Clinic Rochester,  research study entitled: “CAncer Survivor CArdiomyopathy DEtection (CASCADE)”.   
• Lina Shehadeh, PhD,  University of Miami, research study entitled: “Anti-Osteopontin Monoclonal Antibody Therapy in a Pig Model of Atherosclerosis”.  
• Gervasio A. Lamas, MD/Christos Mihos, DO,  Mount Sinai Medical Center,  research study entitled: “Effects of Exercise and FITness on Left Ventricular Torsion and Wall MechanIcs STudy (FIT-TWIST)”.  
• Brian Shapiro, MD/Bryan Taylor, PhD, Mayo Clinic Jacksonville,  research study entitled: “Exercise Training to Improve Pulmonary Haemodynamic and Right Ventricular Function in Heart Failure Patients with Pulmonary Hypertension”.    

2020 CONTINUED RESEARCH RECIPIENTS/PROJECTS:  

• Jose A Adams, MD, Mount Sinai Medical Center, research study entitled: "Whole Body Periodic Acceleration (pGz) in Heart Failure".  
• Joerg Herrmann, MD, Mayo Clinic Rochester,  research study entitled: "TACTIC - TrAstuzumab Cardiomyopathy Therapeutic Intervention with Carvedilol Trial". 
• Chunming Dong, MD, University of Miami,  research study entitled: "MicroRNA Regulation of Cocaine Effects in the Cardiovascular System".  
• Jeffrey J Goldberger, MD, University of Miami, research study entitled: "4D Flow MRI for Assessment of Left Atrial Stasis". 
• Lina Shehadeh, PhD, University of Miami,  research study entitled: "The Role of Osteopontin in Heart Failure with Preserved Ejection Fraction".  
• Raul Mitrani, MD, University of Miami,  research study entitled: “Anti-arrhythmic Effects of Mesenchymal Stem Cell Injection in a Swine Model of Post Myocardial Infarct Ventricular Tachycardia". 
• Nanette Bishopric, MD, Georgetown University,  research study entitled: "Restoration of Heart Function by Novel Chemical Probes Targeting Remodeling in the Ischemic Heart". 
• Nanette Bishopric, MD, Georgetown University,  research study entitled: “Reversal of Hypertrophy: Feasibility, Safety and Biological Consequences”.  
• Sana Nasim, PhD Candidate, Florida International University,  research entitled: "Phenotypic and functional characterization of neural crest derived-aortic valve interstitial cells".   
• Gervasio A. Lamas, MD, Mount Sinai Medical Center, research study entitled: "Trial to Assess Chelation Therapy 3a (TACT3a)".
• Jose R. Lopez, MD, Mount Sinai Medical Center, research study entitled: “Cardioprotection in Diabetic Cardiomyopathy via upregulation of ATP-sensitive K+ channels”.   
• Sharan Ramaswamy, PhD, Florida International University,  research entitled: "Stem Cell-seeded bioscaffolds supporting somatic growth, function and remodeling in the treatment of critical congenital valve disease in the young".     

2019 RESEARCH RECIPIENT/PROJECTS:

• Nanette Bishopric, MD, Georgetown University, research study entitled: "Restoration of Heart Function by Novel Chemical Probes Targeting Remodeling in the Ischemic Heart".
• Nanette Bishopric, MD, Georgetown University, research study entitled: “Reversal of Hypertrophy: Feasibility, Safety and Biological Consequences”.
• Chunming Dong, MD, University of Miami, research study entitled "MicroRNA Regulation of Cocaine Effects in the Cardiovascular System".
• Jeffrey J Goldberger, MD, University of Miami, research study entitled "Novel Assessments in Atrial Fibrillation".
• Lina Shehadeh, PhD, University of Miami, research study entitled "The Role of Osteopontin in Heart Failure with Preserved Ejection Fraction".
• Raul Mitrani, MD, University of Miami, research study entitled “Anti-arrhythmic Effects of Mesenchymal Stem Cell Injection in a Swine Model of Post Myocardial Infarct Ventricular Tachycardia".
• A. Allen Seals, MD, Florida Cardiovascular Quality Network Foundation, research study entitled “Florida Cardiovascular Quality Network Hyperlipidemia: Application of Clinical Decision Support Software Tools at the Point of Care in Patients with Hyperlipidemia—a Quality Outcomes Registry”

 2018 - 2019 SUPPLEMENTAL RESEARCH RECIPIENTS/PROJECTS:

• Gervasio A. Lamas, MD, Mount Sinai Medical Center, research study entitled: "Trial to Assess Chelation Therapy 3a (TACT3a)".
• Jose R. Lopez, MD, Mount Sinai Medical Center, research study entitled “Cardioprotection in Diabetic Cardiomyopathy via upregulation of ATP-sensitive K+ channels”.
• Sharan Ramaswamy, PhD, Florida International University, research entitled "Stem Cell-seeded bioscaffolds supporting somatic growth, function and remodeling in the treatment of critical congenital valve disease in the young"
• Sana Nasim, PhD Candidate, Florida International University, research entitiled "Phenotypic and functional characterization of neural crest derived-aortic valve interstitial cells"

2018 RESEARCH RECIPIENTS/PROJECTS:

• Nanette Bishopric, MD, University of Miami, research study entitled: "Restoration of Heart Function by Novel Chemical Probes Targeting Remodeling in the Ischemic Heart".
• Chunming Dong, MD, University of Miami, research study entitled "MicroRNA Regulation of Cocaine Effects in Atheroslerosis".
• Jeffrey J Goldberger, MD, University of Miami, research study entitled "4D Flow MRI for Assessment of Left Atrial Stasis".
• Lina Shehadeh, PhD, University of Miami, research study entitled "The Role of Osteopontin in Heart Failure with Preserved Ejection Fraction".
• Lina Shehadeh, PhD, University of Miami, research study entitled "New Model and Novel Therapies for Heart Failure with Preserved Ejection Fraction”
• Joshua M. Hare, MD, University of Miami,  research study entitled “Biomarker analysis from the POSEIDON-DCM – The PercutaneOus StEm Cell Injection Delivery Effects On Neomyogenesis in Dilated CardioMyopathy”
• Claudia Rodrigues, PhD, University of Miami, research study entitled “Molecular Mechanisms of Anthracycline-Induced Cardiovascular Toxicity”
• Brian Shapiro, MD, Mayo Clinic Jacksonville, research study entitled "Diagnostic Utility of Exercise Cardiac Magnetic Resonance in the Assessment of Cardiac Dyspnea”
• Nanette Bishopric, MD, University of Miami, research study entitled: “Reversal of Hypertrophy: Feasibility, Safety and Biological Consequences”