College of Graduate Studies

Summer Research Programs - Cardiovascular Research

Cardiac Hypertrophy and Failure
When the heart is stressed by having to pump blood against increased pressure, it adapts by increasing its muscle mass. Long-term hypertrophy often leads to congestive heart failure. The changes in the regulation of transcription and translation resulting from hemodynamic overload, and the identification of the signal mechanisms responsible for initiating and maintaining these processes in hypertrophy and those leading to failure, are under investigation at MUSC. The molecular processes and genetics that play a causative role in the cardiomyopathy associated with chronic tachycardia are also being investigated.

Participating Investigators:

Amy Bradshaw, PhD., Associate Professor, Medicine/Cardiology
Regulation of extracellular matrix

John S. Ikonomidis, MD, PhD., Professor, Surgery/Cardiothoracic Surgery
Extracellular matrix remodeling in thoracic aortic aneurysm disease

Jeffrey Jones, PhD., Assistant Professor, Surgery/Cardiothoracic Surgery
Extracellular matrix remodeling in thoracic aortic aneurysm disease

Dhan Kuppuswamy, PhD., Associate Professor, Medicine/Cardiology
Protein kinase signaling in hypertrophying myocardium; regulation of Src family kinases in adult heart

Martin Morad, PhD., Professor, Regenerative Medicine and Cell Biology
Cellular and subcellular signaling processes

Don Menick, PhD., Professor, Medicine/Cardiology
Regulation of gene expression in heart disease, Role of HDACs in heart disease

Paul McDermott, PhD., Professor, Medicine/Cardiology
Translational control in the hypertrophied heart, regulation of protein synthesis during cardiac growth

Rupak Mukherjee, PhD., Associate Professor, Surgery
Cardiac wound healing and fibrosis, cardiac physiology

Terrence O'Brien, MD, Professor, Medicine/Cardiology
Genetic control mechanism in the myocyte, signaling pathways that regulate mitochondrial biogenesis during development of cardiac hypertrophy

Michael Zile, MD, Professor, Medicine/Cardiology
Collagen and myocyte flexibility, intra-and extracellular mechanisms of diastolic function and diastolic heart failure
Developmental Cardiac and Stem Cell Biology
The role of cellular movements and interactions, growth factors and extracellular matrices in the differentiation and morphological formation of the embryonic heart, its conduction system and the morphogenesis of blood vessels is being studied by this group of investigators. Embryonic stem cell and hematopoietic stem cell differentiation are also foci of research.

Participating Investigators:

Kelley M. Argraves, PhD., Assistant Professor, Regenerative Medicine and Cell Biology
Role of sphingosine-1-phosphate in vasculogenesis and angiogenesis

W. Scott Argraves, PhD., Professor, Regenerative Medicine and Cell Biology
Extracellular matrix biology; lipoprotein metabolism

Chritophers Drake, PhD., Professor, Regenerative Medicine and Cell Biology
Control and regulation of neo-vascular processes (angiogenesis & vasculogenesis), stem cell biology

Christi Kern, PhD., Assistant Professor, Regenerative Medicine and Cell Biology
Role of the extracellular matrix (ECM) during cardiovascular development

Michael J. Kern, PhD., Professor, Regenerative Medicine and Cell Biology
Homeobox genes in cardiac development and function

Steven Kubalak, PhD., Associate Professor, Regenerative Medicine and Cell Biology
Mechanisms of endocardial cushion morphogenesis, TGF-beta regulation of apoptosis

Kyu-Ho Lee, PhD., MD, Assistant Professor, Pediatric Cardiology/Regenerative Medicine and Cell Biology
Mechanisms causing congenital heart disease in humans

Roger Markwald, PhD., Professor, Regenerative Medicine and Cell Biology
Cardiac morphogenesis

Robin Muise-Helmericks, PhD., Assistant Professor, Regenerative Medicine and Cell Biology Molecular and cellular mechanisms involved in (1) vasculo/angiogenesis and (2) lymphoid development

Chip Norris, PhD., Assistant Professor, Regenerative Medicine and Cell Biology
Formation of the cardiac valves and pathological processes that result in valve disease

Ann Ramsdell, PhD., Assistant Professor, Regenerative Medicine and Cell Biolog
Morphogenetic and molecular mechanisms that direct generationof cardiac left-right asymmetry

J. PhilipSaul, MD, Professor, Pediatrics
Cardiac conduction, differentiation and mechanics, interventional electrophysiology, radiofrequency catheter techniques

Richard Visconti, PhD., Assistant Professor, Regenerative Medicine and Cell Biology
Role of the extracellular matrix (ECM) during cardiovascular development

Arno Wessels, PhD., Professor, Regenerative Medicine and Cell Biology
Developmental events leading to congenital heart Malformation
Diabetes
Major areas of diabetes research that are conducted at MUSC include identification of the mechanisms of insulin action and resulting metabolic syndrome; the genetics of diabetes and its complications; interactions between lipoproteins and arterial vessel walls to promote plaque formation and ultimately atherosclerosis; diabetic eye diseases; the role and contribution of the kallikrein-kinin system; and the pathogenesis of diabetic vascular and renal disease.  In addition to the above areas of investigation, students can also conduct research in the MUSC Diabetes Center.  The center incorporates patient care for diabetic patients, the DCCT/EDIC Clinical Center at MUSC, and the Diabetes Initiative of South Carolina.  The center is a component of the Division of Endocrinology, with a mission to promote the optimal care of diabetic patients through development of model systems, outreach, education and health delivery research.

Participating Investigators:

Rosalie Crouch, PhD., Professor, Opthalmology
Structure/function of retinoid binding proteins

Brent Egan, MD, Professor, Internal Medicine
Metabolic syndrome

Mark Kindy, PhD., Professor, Neurosciences
Oxidized lipoproteins in neurodegeneration

Dan Lackland, DrPH, Professor, Neurosciences
Epidemiology of cardiovascular disease, hypertension, and diabetes

Maria Lopes-Virella, MD, PhD., Professor, Medicine/Endocrinolg
Pathogenesis of atheroscierosis; regulation of LDL receptor expression

Louis Luttrell, MD, PhD., Professor, Medicine/Endocrinology
Signal transduction, G protein-coupled receptors
Renal and Vascular Pathophysiology
Research into the basic mechanisms underlying the causes of renal and vascular dysfunction in disease states such as diabetes, hypertension, and insulin resistance are being studied.  Major areas of investigation include identification of the role of G-protein coupled receptors (kinin, angiotensin II, serotonin) and cytokine receptors such as TGF-β11 in the initiation and progression of glomerular injury, glomerular hemodynamics and glomerular morphology; genomics and proteomics to identify risk markers of renal disease in humans and animal models of ESRD; and mechanisms of endothelial dysfunction and the role of nitric oxide and reactive oxygen species in the regulation of vascular tone and ultrastructure.  Opportunities in both basic and clinical science are available to the students in this area of research.  

Participating Investigators:

W. Scott Argraves,PhD., Professor, Regenerative Medicine and Cell Biology
Extracellular matrix influences on cellular migration and growth, lipoprotein receptor biology

John Arthur, MD, PhD., Professor, Medicine/Nephrology
Salt and water physiology; proteomics technology development

Craig Beeson, PhD., Associate Professor, Drug Discovery and Biomedical Science
Energy metabolism regulation and cell cycle progression

Julie Chao, PhD., Professor, Biochemistry and Molecular Biology
Regulation and function of renal kallikrein

James Cook, PhD., Professor, Neurosciences
Role of eicosanoids in shock

Christopher Drake, PhD., Professor, Regenerative Medicine and Cell Biology
Control and regulation of neo-vascular processes, stem cell biology

Brent Egan, MD, Professor, Pharmacology & Experiemental Therapeutics
Metabolic syndrome

Gary Gilkeson, MD, Professor, Medicine/Rheumatology
Molecular and pathogenic studies of systemic lupus erythematosus (SLE)

Sergey Krupenko,PhD., Professor, Biochemistry and Molecular Biology
Enzyme mechanisms and enzyme regulation

Maria Lopes-Virella, MD, Professor, Medicine, Pathology
Pathogenesis of atherosclerosis; regulation of LDL receptor expression

Paul McDermott, PhD., Professor, Medicine/Cardiology
Regulation of protein synthesis during cardiac growth

Donald Menick, Ph.D., Professor, Medicine/Cardiology
Na+-Ca2+ exchangers in cardiac hypertrophy and failure

James Oates, MD, Associate Professor, Medicine/Rheumatology
Pathogenic role of nitric oxide (NO) and its oxidative metabolites

Terrence O' Brien, MD, Professor, Medicine/Cardiology
Signaling pathways in cardiac hypertrophy

Michael Zile, MD, Professor, Medicine/Cardiology
Intra- and extracellular mechanisms of diastolic function and heart failure
Signal Transduction and Human Disease

Delineating the mechanisms that lead to the generation and processing of inter- and intracellular signals in disease processes are a major focus of investigation at MUSC.  Major areas include identification of second messenger molecules in sclerosis of renal and vascular cells; G-protein coupled receptor signaling and renal disease; MAPK signaling pathways in the control of transcription factors; TGF-β signaling in promoting fibrosis of renal and vascular cells; normal and modified lipoprotein signal transduction pathways and vascular remodeling; insulin signal transduction pathways and translocation of glucose transporters; novel mechanisms of protein kinase C regulation by diacylglycerol and insulin resistance; and regulation of cellular levels of sphingosine-1-phosphate, a bioactive lipid that works through binding to its G-protein coupled receptor to mediate proliferation, migration and angiogenesis.  These studies have important implications to neoproliferative blood vessels in diabetic retinopathy and nephropathy.  Many of the training opportunities in this area of investigation are in the basic science disciplines.

Participating Investigators:

Narendra Banik, PhD., Professor, Neurology
Myelination and myelin metabolism

Amy Bradshaw, PhD., Associate Professor, Medicine/Cardiology
Regulation of extracellular matrix

Kenneth D. Chavin, MD. PhD., Professor, Surgery
Liver transplantation, liver regeneration, and mitochondrial uncoupling proteins

Rosalie Crouch, PhD., Professor, Opthalmology
Structure/function of retinoid binding proteins

Judy Dubno, PhD., Professor, Otolaryngology
Impact of hearing impairment and aging on the ability to process sound and understand speech

John Hildebrandt, PhD., Professor, Cell & Molecular Pharmacology
Hormone-regulated GTP-binding proteins

Mark Kindy, , PhD., Professor, Physiology and Neuroscience
Oxidized lipoproteins in neurodegeneration

Dhan Kuppuswamy, PhD., Associate Professor, Medicine/Cardiology
Nonreceptor tyrosine kinases mediated signaling int he heart

Maria Lopes-Virella, MD, PhD., Professor, Medicine/Endocrinology
Pathogenesis of atherosclerosis; regulation of LDL receptor expression

Louis Luttrell, MD. PhD., Professor, Medicine/Endocrinology
Signal transduction, G protein-coupled receptors

Terrence O'Brian, MD, Professor, Medicine/Cardiology
Signaling pathways in cardiac hypertrophy

Rick Schnellmann, PhD., Professor, Drug Discovery & Biomedical Science
Mechanisms of cell injury, death, repair, and regeneration

Rita Young, PhD., Professor, Medicine/Hematology
Tumor induced immunosuppression

Health Disparities

Of special concern to MUSC physicians and scientists are a group of diseases and disorders that exhibit significantly higher rates of incidence, morbidity, and mortality among the residents of South Carolina and in particular the African American population of South Carolina than among other population groups or even African Americans in other parts of the country.  Notable among these health concerns are diabetes mellitus, obesity, insulin resistance and chronic renal failure.  Other on-going studies at MUSC that specifically address heath disparities include the Charleston Study of Kidney Disease in African Americans (AASK Study); Project Sugar that studies positional cloning of diabetes-related genes among Gullah-speaking African Americans from the coastal SC “sea islands”; a research program project grant funded by AHRQ titled “Understanding and Eliminating Minority Health Disparities”; a national “Resource Center for Minority Aging” funded by the N1A; and the Multidisciplinary Clinical Research Center (MCRC) for the Study of Rheumatic Diseases in African-Americans.  Sarcoidosis and sickle cell anemia are also the subject of concerted laboratory and patient-oriented research efforts, including participation in NIH-supported clinical consortia conducting research for these special diseases.

Participating Investigators:

Brent Egan, MD, Professor, Medicine, Cell & Molecular Pharmacology & Experimental Therapeutics
Metabolic syndrome

Leonard E. Egede, MBBS, MSCR, Professor, Medicine
Improving diabetes outcomes, metabolic syndrome, health disparities

Esther Forti, PhD., Associate Professor, Health Professions
Rural health policy, health disparities, geriatrics, and long-term care issues

Gary Gilkeson, MD, Professor, Medicine/Rheumatology
Molecular and pathogenic studies of systemic lupus erythematosis (SLE)

Mark A. Judson, MD, Professor, Medicine/Pulmonary
Sarcoidosis, diseases of the lungs in immuno-compromised patients, aspergillus lung disease

Daniel T. Lackland, DrPH, Professor, Neurosciences & Medicine
Epidemiology of cardiovascular disease, hypertension, diabetes and chronic disease, fetal origins of adult chronic disease; population-based epidemiology studies

James Oates, MD, Associate Professor, Medicine/Rheumatology
Pathogenic role of nitric oxide (NO) and its oxidative metabolites

Richard M. Silver, MD, Professor, Medicine/Rheumatology
Pathogenesis of scleroderma lung disease

New Technologies and Human Disease Research

The disciplines of genomics and proteomics cannot be uncoupled from bioinformatics, the tools to handle and analyze the prodigious amounts of data that continue to emerge from large scale DNA, RNA, and protein projects.  The application of these technologies to specific biological problems provides a new model for approaching research into human diseases.  Similarly, the rapid progression of imaging tools (magnetic resonance imaging MRI, PET, etc.) has produced powerful machines that provide in vivo chemical, structural, and functional imaging of human and animal anatomy, physiology, and chemistry.  Students can receive training in the emerging areas of (1) proteomics – MUSC has exceptional strength in this area and was recently awarded one of ten NHLBI Proteomics Center contracts nationwide, providing $15.3 million over 7 years to enhance and develop innovative proteomic technologies and apply them to relevant biological questions. (2) bioinformatics – a formal training program in informatics spans a spectrum of computational activities including algorithm development for sequence alignment, clustering for microarrays and protein chips, statistical issues in genome analysis, computer-aided diagnostics, and health outcome modeling.
(3) functional imaging – MUSC’s Center for Advanced Imaging offers students opportunities to study depression and other behavioral disorders associated with diabetes and its complications. (4) gene therapy – The rationale for applying gene therapy to human disease is now well established with a number of disease categories directly amenable to therapeutic intervention, but gene delivery issues have hampered the advancement of many studies.  New and novel adenoviral and AAV delivery systems constitute promising and exciting research areas that require further development.

Participating Investigators:

W. Scott Argraves, PhD., Professor, Regenerative Medicine and Cell Biology
Extracellular matrix; LDL receptors; DNA microarrays

John Arthur,MD, PhD., Professor, Medicine/Nephrology
Salt and water physiology; proteomics technology development

Thomas Dix, PhD., Associate Professor, Drug Discovery and Biomedical Science
Rational drug design, with a focus on peptide-based therapeutics

 
 
 

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