Peter C. Gazes Cardiac Research Institute

Associate Professor - Division of Cardiology

Biography

Dr. Amoroso is an interventional cardiologist who specializes in catheter-based procedures and innovation for the treatment of heart valve disorders (aortic/mitral/tricuspid/pulmonic), cardiac septal defects (PFO/ASD/VSD), coronary artery disease (stents/PCI/complex coronary interventions), and stroke prevention with left atrial appendage occlusion.

Originally from the Washington, D.C. area, he went on to medical school at George Washington University followed by internal medicine residency at NYU in New York City. He completed his cardiovascular disease fellowship at Mount Sinai Beth Israel and returned to NYU for advanced fellowship training in interventional cardiology with a dedicated training for transcatheter structural heart disease interventions (TAVR/Mitraclip/TMVR/valvuloplasty/PFO closure/ASD closure/PVL closure/etc).  He is board-certified in internal medicine, cardiovascular disease, interventional cardiology, echocardiography, nuclear cardiology, and vascular imaging interpretation.

During his career, he has participated in numerous cutting-edge clinical trials, published research in leading cardiology journals, and is a regular speaker at national conferences. His academic interests focus on innovation in the treatment of valvular heart disease and coronary artery disease but, he most values taking care of patients.In his personal time, he enjoys travel, lacrosse, Charleston's food culture, and spending time with his wife and children.

Associate Professor - Division of Cardiology

Research Profile

My long-standing research interest is in the area of cardiac biomechanics. Specifically, the contractile and viscoelastic mechanical properties of cardiac biomaterials represent the focus and commitment of my research efforts. In the Zile laboratory, we perform multiple experimental studies in small and large animal models of cardiac disease, especially cardiac hypertrophy and heart failure induced by pressure overload. We continue to work closely with many collaborating investigators to evaluate various indices of cardiovascular function in our animal models of heart disease. My mentor, Michael Zile, M.D., and I closely collaborate on multiple basic, translational, and clinical research projects to define the extracellular molecular mechanisms that cause the development of myocardial remodeling, diastolic dysfunction, and chronic heart failure.

Our research laboratory has been supported by grants from the National Heart, Lung and Blood Institute, American Heart Association, Medical University of South Carolina, National Aeronautics and Space Administration, US Department of Veterans Affairs, and US Department of Defense.

Professor - Division of Cardiology

Research Profile

The Bradshaw laboratory is focused on cellular mechanisms controlling procollagen processing and collagen deposition in cardiac fibrosis and in periodontal ligament repair.

A fundamental question in cell biology is how cells regulate the synthesis and construction of tissue-specific extracellular matrices (ECMs) in their environment and, in turn, how changes in the structure and composition of the ECM can influence cell behavior in response to injury and disease. In particular, we are interested in cellular mechanisms of collagen fibril assembly in the ECM and the function of matricellular proteins in the regulation of this process. Matricellular proteins are defined as proteins that associate with the ECM but do not contribute structurally to the ECM in contrast to classical ECM proteins such as collagen and laminin. We have established that one matricellular protein, SPARC (secreted protein acidic and rich in cysteine, osteonectin, BM-40), influences the formation of collagen I fibers in connective tissues of mice. For example, collagen accumulation associated with cardiac pressure-overload hypertrophy is significantly reduced in SPARC-null mice. Elucidation of pathways by which SPARC and other collagen binding proteins influence collagen incorporation and stability in the ECM can lead to the design of strategies to control fibrotic processes in the heart and in other tissues. Alternatively, in diseases in which collagenous tissue is degraded, such as in periodontal disease, factors that improve collagen assembly could be used as essential tools to restore damaged tissues.

Recently, my laboratory defined a novel role of SPARC in regulating the activity of transglutaminase in collagen fibril assembly. We reported that inhibition of transglutaminase activity altered collagen content, fibril diameter, and mechanical properties of tissue. As transglutaminase is highly expressed by macrophages, an interesting speculation is functional differences in collagen deposition might be tightly regulated by macrophage expression of transglutaminase and SPARC thus contributing to the disorganized fibrotic deposition of collagen in disease. The Bradshaw laboratory has been supported by grants from the National Heart, Lung and Blood Institute, the American Heart Association, the Medical University of South Carolina, and the US Department of Veterans Affairs.
 

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Associate Professor - Division of Cardiology

Professor - Division of Cardiology
Director, Christie Heart and Brain Center and Human Heart Biobank

Research Profile 

Dr. del Monte’s lab focuses on basic cardiac muscle pathophysiology and translational research to understand the pathogenesis of cardiomyopathies and heart failure (HF) as an Alzheimer’s disease and for the discovery of novel therapies. The lab utilizes an interdisciplinary approach in-vitro and in-vivo physiology, molecular biology and imaging as well as biophysical and structural-chemistry approaches. The early work from Dr. del Monte’s lab focused on Ca2+ homeostasis in the failing heart and gene therapy. For those studies, Dr. del Monte is a recognized leader in cardiomyocytes physiology and Ca2+ handling in animal models and human hearts. Dr. del Monte’s research has evolved towards cutting edge and innovative unexplored territories linking Alzheimer’s Disease and heart failure. The latest discoveries are recognized as a major breakthrough that opened a new era for the understanding of the pathogenesis of HF.

Dr. del Monte discovered, in dilated cardiomyopathy (iDCM), plaque and tangles-like protein aggregates similar to the pathological defects in Alzheimer Disease (AD). Since this first discovery the lab determined that Alzheimers Disease and cardiomyopathy share the same pathogenic defect changing the paradigm of the pathogenesis of iDCM. The lab characterized the cell response to misfolded proteins; identified genetic variants in common between iDCM and AD; purified and chemical characterized the composition of amyloid fibrils of cardiac plaques identifying an actin-polymerizing protein-Cofilin-2 to be comprised within the aggregates and characterized its role on cardiac function; identified how misfolded proteins exert their toxic effect and developed the new concept of metastatic transmissibility of pre-amyloid oligomers.

In addition to identifying Alzheimer’s like plaques and tangles in the heart of patients with cardiomyopathy the lab determined that the heart of patients with primary diagnosis of Alzheimer’s contains Ab deposits and present diastolic dysfunction. Given the commonality of the structure/function of misfolded proteins, the results obtained on cardiomyocytes can be translated to any cell, and studying the heart can provide insights for the detection of onset and progression of brain disorders using the heart as a window to the brain and offering a common therapeutic target for diseases affecting millions of people. Supporting activities for the cardiology division are mentoring students and fellows, from experience as reviewer for K08, K99-R00, R01 NIH grants. Dr. del Monte is also the Director of the human hearts biorepository at MUSC.

Christie Heart & Brain Program

Human Hearts Biorepository (Biobank)

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Associate Professor - Division of Cardiology

Biography

Dr. DeLeon-Pennell was trained in cardiovascular sciences at Baylor University, University of Texas Health Science Center San Antonio, and the University of Mississippi Medical Center.  She has >10 years’ experience with all aspects of the inflammatory and fibrotic components of cardiac remodeling following a heart attack. Her current research projects focus on the role of the adaptive immune system and how it interplay with the innate immune system to regulate cardiac wound healing. This includes evaluating how existing confounding variables such as gender or aging changes these processes.

Research Profile

The DeLeon-Pennell Lab focuses on all aspects of the inflammatory and fibrotic components of cardiac remodeling following a heart attack (myocardial infarction; MI). This includes evaluating how existing variables such as gender or aging changes these processes. Our major research focus is on the role of the adaptive immune system and the interplay with the innate immune system to regulate cardiac wound healing. These changes include cell-cell and cell-matrix interactions, which both affect and react to processes involved in tissue repair.

Overall our goal is to:

1. Develop multidimensional approaches to examine the mechanisms whereby the innate and adaptive immune system influences cardiovascular remodeling
2. Understand the dynamics and function of bio-molecules involved in cardiac remodeling
3. Improve current therapeutic strategies to prevent, slow, or reverse the progression to heart failure

Recently our lab has identified new mechanisms implicating CD8+ T-cells as regulators of the post-MI wound healing process. Our data indicated without functional CD8+ T-cells there was a decrease in left ventricular dilation and improved mortality post MI. In addition CD8+ T-cells were found to facilitate removal of necrotic tissue and the development of the fibrotic scar. The DeLeon-Pennell laboratory has been supported by grants from the National Heart, Lung and Blood Institute, the American Heart Association, the Medical University of South Carolina, and the US Department of Veterans Affairs.

Assistant Professor - Division of Cardiology

Professor - Division of Cardiology

Biography

Dr. Valerian Fernandes received his MBBS degree from St. John's Medical College, Bangalore in 1989 and his post graduate M.D. (internal medicine) degree from Post-Graduate Institute of Medical Education and Research (PGIMER) Chandigarh, India in 1992. He received his MRCP degree in 1994 (Member of Royal College of Physicians-UK). In the U.S. he did his internship at St. Luke-Roosevelt Hospital in New York and completed his internal medicine residency at the Mayo Clinic, Rochester, Minnesota in 1997. His cardiology and interventional cardiology fellowship training was done at the Baylor College of Medicine, Houston, Texas from 1997 to 2001. Since his training, he has been on the MUSC faculty as an assistant professor of medicine and as a staff physician and director of the cardiac catheterization laboratories at the Ralph H. Johnson VA Medical Center.

Dr. Fernandes is board certified in cardiovascular disease and interventional cardiology. He is level III echocardiography trained and certified and also level II nuclear cardiology trained and certified. Dr. Fernandes' clinical and research interests include complex coronary interventions, rotational atherectomy, vulnerable plaque evaluation and treatment, acute coronary syndromes, alcohol septal ablation for hypertrophic obstructive cardiomyopathy, peripheral arterial intervention and Doppler and transesophageal echocardiography. He is the only certified percutaneous mitral valvuloplasty practitioner in the state of South Carolina. Dr. Fernandes has been a principal investigator in several trials and has also co-authored many publications. He is very active in teaching and medical education and has received many teaching awards and nominations. He is a reviewer for medical journals and a fellow of the American College of Cardiology.

Research Profile

Dr. Fernandes’ clinical and research interests include complex coronary interventions, rotational atherectomy, vulnerable plaque evaluation and treatment, acute coronary syndromes, alcohol septal ablation for hypertrophic obstructive cardiomyopathy, peripheral arterial intervention and Doppler and transesophageal echocardiography. He is the only certified percutaneous mitral valvuloplasty practitioner in the state of South Carolina.

Dr. Fernandes has been a principal investigator in several trials and has also co-authored many publications.

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Professor - Division of Cardiology
Volpe SmartState Endowed Chair in Cardiovascular Biomarker Development & Molecular Proteomics

Biography

Dr. Brian Houston is a cardiologist specializing in the management of advanced heart failure, including the care of patients before and after heart transplantation or left ventricular assist device (LVAD). After graduating from Emory University School of Medicine, Dr. Houston completed residency at Johns Hopkins Hospital in Baltimore, Maryland. He was invited to serve as an assistant chief of service of the Thayer Firm at Johns Hopkins Hospital, and he spent that year caring for patients and instructing residents and medical students. He remained at Johns Hopkins for his general cardiology fellowship and spent an additional year of fellowship there training in the care of advanced heart failure, LVADs, and transplantation.

Dr. Houston has been invited to present his research work at international scientific meetings. He has a particular interest in cardiac sarcoidosis and in the effects of LVAD support on the gastrointestinal tract, blood, and the right side of the heart. He was honored to be named a finalist for the American Heart Association's Young Clinician Award in 2015. Dr. Houston believes that each patient with heart failure is unique and that, to live their best life, they require a caring and comprehensive approach from a dedicated medical team.

Program Director General Cardiology, Cardiovascular Genetics
Edwin W. &Teresa H. Rogers Endowed Chair for Cardiovascular Research, and Professor - Division of Cardiology

Biography

As a cardiologist and translational scientist, my research is focused on monogenic forms of cardiovascular disease, with particular emphasis on heart failure. I am the Director of the MUSC Cardiovascular Genetics program and the fellowship director for Cardiovascular Disease at MUSC. My post-doctoral research at Johns Hopkins University was focused on the molecular pathogenesis and translational treatments for Marfan syndrome and other inherited aortic diseases. For the past fifteen years, my research program has focused on the genetic basis and pathogenesis of inherited heart disease, with translational research trials investigating novel therapies targeting key factors involved with disease pathogenesis. 

Research Profile

The Judge lab focuses on inherited cardiovascular disorders, investigating their genetic basis and molecular pathogenesis, in order to identify better therapies for people with these conditions. There are three major areas of investigation:

1. Arrhythmogenic Cardiomyopathy – This inherited form of cardiomyopathy is often caused by mutations in genes encoding cardiac desmosomes, which form junctions between cardiomyocytes. We developed a murine model to serve as platform for studies on this familial form of heart disease. Current projects seek to identify the role of aerobic exercise in worsening this condition, as well as to identify better treatments to prevent fibro-fatty scar formation in the heart.

2. Transthyretin (TTR) Amyloidosis – TTR is a protein produced in the liver, circulating in blood as a carrier protein for thyroid hormone and retinol (vitamin A). Mutations in this gene cause the protein to misfold and deposit in the heart and elsewhere as insoluble amyloid plaques. A wild-type form of this disease occurs without mutations in TTR, and very little is known about its pathogenesis.

3. Familial Mitral Valve Prolapse – Our prior work demonstrated that increased TGF-beta signaling contributes to abnormal growth of the mitral valve leaflets. In collaboration with investigators in the MUSC Department of Regenerative Medicine and Cell Biology, we are investigating genetic factors that contribute to this common form of heart disease.

Professor - Division of Cardiology
Spaulding Paolozzi Endowed Chair

Biography

Dr. Sheldon E. Litwin is a cardiologist with nationally recognized expertise in advanced cardiac imaging and its use in the diagnosis of heart disease and treatment of patients with heart disease. Dr. Litwin is board-certified in general cardiology, nuclear cardiology, echocardiography, and cardiovascular computed tomography (CT). He was recognized in 2014 in America's Top Doctors (Castle Connolly Medical Ltd.). He is a strong proponent of preventive cardiology and has a longstanding interest in weight loss as prevention and treatment for cardiovascular disease. He is an avid outdoorsman and exercise advocate who is passionate about caring for active adults who participate in sports or recreational exercise.

Prior to coming to MUSC Health, Dr. Litwin was chief of the division of cardiology at Georgia Regents University from 2011 to 2014 and director of cardiac imaging at the University of Utah from 1993 to 2011. Dr. Litwin is involved in clinical trials using new therapies for heart failure with preserved ejection fraction (HFpEF). He has published more than 100 scientific papers and serves on several editorial boards and national committees.

Dr. Litwin's medical degree was awarded by Washington University School of Medicine. He completed a residency at the University of Arizona and completed a cardiology fellowship at Beth Israel Hospital, Harvard Medical School.

Professor - Division of Cardiology
Director, Gazes Cardiac Research Institute

Research Profile

My laboratory is focused on the analysis of signaling and gene regulatory pathways, which play a role in cardiac failure. Recently, we have demonstrated that protein acetylation, regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) plays a significant role in modulating gene expression in cardiac pathologies. Importantly, treatment with HDAC inhibitors preserves ventricular remodeling and cardiac function in pre-clinical models of cardiac hypertrophy, myocardial infarction (MI), ischemia reperfusion (IR) and heart failure. We have determined that HDAC inhibitors promote the polarization of inflammatory M1 macrophages to anti-inflammatory M2 macrophages, resulting in reduced deleterious remodeling and preserve cardiac function in the post MI heart.

Our study is the first account of the benefit of HDAC inhibition being due in part to its ability to polarize macrophages, a cellular component underappreciated until recently in cardiac pathologies. Our work has also identified a mechanism that has served as a paradigm of how HDACs can mediate both repression and activation of gene expression. We have also identified an important mechanism whereby HDAC inhibitors can repress cardiac gene expression by altering the acetylation state of co-activator and co-repressors of transcription. We have also shown that the acetylation state of specific transcription factors affects their interaction with co-activators and co-repressors. Therefore, HDACs can facilitate gene activation via the direct deacetylation of transcription factors allowing for recruitment of co-activators to the promoter. Our overall goal is to translate our basic and pre-clinical discoveries into important new therapies for patients with heart disease.

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Dr. Prins is a Professor of Medicine in the Division of Cardiology and Director of the Gazes Cardiac Research Institute at MUSC. He trained at the University of Alabama-Birmingham and then completed an integrated research and clinical cardiology fellowship at the University of Minnesota. He also runs a NIH-funded laboratory aimed at understanding and treating right heart failure and pulmonary hypertension. Dr. Prins cares for patients with multiple cardiovascular diseases. He is particularly interested in right heart failure, tricuspid regurgitation, dyspnea, and pulmonary hypertension.

Assistant Professor - Division of Cardiology

Assistant Professor - Division of Cardiology

Professor - Division of Cardiology
Director, Advanced Heart Failure & Transplant Cardiology Fellowship Program

Research Profile

Dr. Tedford is an internationally recognized clinical researcher and has published over 100 peer-reviewed original research manuscripts, invited expert reviews, editorials and book chapters. His research efforts are focused on hemodynamic assessment of right ventricle function and its interaction with the pulmonary circulation and left heart. This spans the fields of pulmonary hypertension, left heart disease, exercise physiology, systemic sclerosis, cardiac transplantation and mechanical circulatory support. His group is currently investigating the diagnostic and prognostic value of right ventricular reserve and is relation to resting RV-PA coupling.

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Assistant Professor - Division of Cardiology

Research Profile

Dr. Wehbe is the primary investigator of the Heart AI Lab (HEAL). HEAL is a team of researchers in the Division of Cardiology and Biomedical Informatics Center (BMIC) at the Medical University of South Carolina (MUSC) dedicated to using artificial intelligence to improve the health of patients living with cardiovascular disease, with a particular focus on heart failure. HEAL boasts an expanding program of both collaborative and internal research. Using innovative approaches to develop and apply cutting-edge deep learning methodologies, we analyze multi-modal unstructured data—such as cardiac imaging, electronic health records, and sensor data—to uncover new pathophysiologic insights, improve diagnostics, and enhance patient care. HEAL strives to bridge the gap between artificial intelligence and cardiovascular medicine, driving impactful research with real-world applications.

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Distinguished University Professor
Charles Ezra Daniel Endowed Chair
Division of Cardiology

Research Profile

Effective management of patients with chronic heart failure (CHF) remains one of the most critical unmet needs in cardiology in the United States and in the world. The fundamental goals of our research efforts over the last 35 years have been to define the ventricular, myocardial, cellular, and molecular mechanisms that cause the development and the progression of CHF and then to use these identified mechanisms as targets to improve diagnostic techniques, prognostic prediction, and therapeutic management of patients with CHF. In particular, I have focused my efforts on the clinical syndrome of heart failure (HF) with a preserved ejection fraction (HFpEF). More than 50% of all HF patients have HFpEF. HFpEF results in morbidity and mortality rates that are staggering: 50 to 60% 5-year mortality rate, 50% 6-month rehospitalization rate, and severe clinical disability. However, as stated in the current HF guidelines: “to date, no treatment management strategies have yet been shown, convincingly, to reduce morbidity or mortality in patients with HFpEF”.

Together with collaborators, we have developed state-of-the-art imaging techniques to characterize the structural and functional remodeling that occur in CHF patients. In addition, we have applied these techniques in an echocardiographic core laboratory used for all of our clinical, translational, and basic science studies. We have also developed clinically relevant animal models of human disease, state-of-the-art methods to assess cardiovascular remodeling, extracellular matrix homeostasis and myocardial function, and applied innovative advanced progenitor cell, transgenic and viral-based alterations in gene expression, translation, and activity to define the pathophysiologic mechanisms underlying CHF.

The Zile laboratory has been supported by research grants from the National Heart, Lung and Blood Institute, the American Heart Association, the Medical University of South Carolina, the National Aeronautics and Space Administration, the United States Department of Veterans Affairs, the United States Department of Defense.

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