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Vascular biology and atherothrombosis

Metabolism, obesity and metabolic diseases

Developmental biology and congenital anomalies

Pulmonary biology and disease

Ion channels and arrhythmias

Muscle biology and heart failure

Prediction and prevention of cardiovascular disease

Advanced technologies

Brian L Black, Ph.D. Professor Research Interests: Cardiac and skeletal muscle development, differentiation, and function Summary: Congenital heart anomalies are the most common form of birth defect in the United States, affecting nearly one percent of all babies, yet the molecular and developmental basis for these defects is largely unknown. Tissues and organs form during mammalian embryonic development because of the integration of numerous signaling and transcriptional pathways. Our major goal is to define these pathways in order to understand the molecular causes of congenital anomalies and potential mechanisms for organ regeneration and repair. Using the mouse as a model system, the current work in the lab is focused on defining the pathways regulating the development of cardiac and skeletal muscle, the vascular endothelium, and neural crest. Specific projects focus on the regulation and function of genes that are known to be critical for cardiac development. These include Mef2c, Islet1, Gata4, Bmp4, and Fgf8. Each of these genes is involved in cardiac development, and we are defining their regulation and function specifically during the formation of the cardiac outflow tract, one of the most commonly and severely affected regions of the heart observed in babies. The long-term scientific goal of these studies is to define the how tissues and cells are integrated during organogenesis and how cells receive and interpret positional information. We are using a combination of conditional gene knockouts, transgenic reporter assays, and fate mapping techniques in mice to define the embryological origins of the outflow tract and the reciprocal signaling between tissues that is required for proper heart development. The ultimate goal of these studies is to development diagnostic and therapeutic interventions for birth defects of the heart and other organ systems.

Elias H Botvinick, M.D. Professor In Residence Research Interests: Nuclear medicine, nuclear cardiology, PET/CT, MRI, CT, cardiac cardiology, echocardiology, nuclear magnetic resonance, cardiovascular imaging, stress testimg, heart, myocardial perfusion, scintigraphy, coronary, sychrony, sychronization Summary: My research centers on a collaborative effort to develop noninvasive imaging methods for the identification and evaluation of cardiac anatomy and pathophysiology, and apply them to the diagnosis, risk stratification and monitoring of clinical disease. The work is centered on nuclear medicine methods, PET and SPECT, as well as echocardiography, MRI, and CT.

Michael S Conte, M.D. Chief, Vascular Surgery Research Interests: Aortic reconstruction, carotid artery disease, lower extremity arterial occlusive disease, diabetic vascular disease Summary: Our laboratory studies the healing process in blood vessels which currently limits the long term success of procedures like angioplasty and bypass surgery. Our goals are to develop new drug and molecular therapies to prevent failures due to vessel re-narrowing, and to better identify patients at increased risk.

Jeffrey R Fineman, M.D. Professor in Residence Research Interests: Endothelial regulation of the pulmonary circulation during normal development and during the development of pediatric pulmonary hypertension disorders. Endothelial dysfunction in pediatric pulmonary hypertension Summary: Pulmonary hypertension, high blood pressure in the lungs, is a serious disorder in subsets of neonates, infants, and children. These include newborns with persistent pulmonary hypertension of the newborn (PPHN), children with congenital heart defects, and teenagers and young adults with primary pulmonary hypertension. The vascular endothelium (the cells that line the blood vessels in the lungs), via the production of vasoactive factors such as nitric oxide and endothelin-1, are important regulators of the tone and growth of pulmonary blood vessels. We utilize an integrated physiologic, biochemical, molecular, and anatomic approach, to study the potential role of aberrant endothelial function in the pathophysiology of pulmonary hypertensive disorders. To this end, we utilize fetal surgical techniques to create animal models of congenital heart disease, and investigate the early role of endothelial alterations in the pathophysiology of pulmonary hypertension secondary to congenital heart disease with increased pulmonary blood flow. Our clinical research interests include the use of pulmonary vasodilator therapy for pediatric pulmonary hypertension, and the use of peri-operative BNP levels as marker of outcome following repair of congenital heart disease.

Yuet W Kan, M.D. , D.Sc. Professor Research Interests: The mechanisms of globin production and exploring novel ways of inserting genes into mammalian cells; investigating newer approaches for fetal diagnosis of genetic disorders Summary: Sickle cell anemia and thalassemia are the most common genetic diseases and affect people of African, Mediterranean, Middle Ease and Southeast Asian origins. Our laboratory has pioneered the diagnosis of these conditions by DNA tests and is currently investigating the use of patient specific stem cells for their treatment.

John P Kane, M.S., M.D., Ph.D. Prof Research Interests: Structure and function of lipoproteins; genetic determinants of arteriosclerosis Summary: The Kane laboratory focuses on the discovery of the native structures of lipoproteins ( proteins that carry cholesterol so that we can better understand how they are involved in the development of heart disease and stroke. We are also active in the discovery of alterations in genes that lead to heart disease and stroke.

Theodore W Kurtz, M.D. Prof in Res & Vice Chair Research Interests: Molecular Genetics of Complex Disease, Genetic Models of Hypertension and the Metabolic Syndrome, Transcription Modulating Drugs Summary: Hypertension affects 30% of the population and is a major cause of stroke, kidney failure, and heart disease. Patients with hypertension are also at increased risk for diabetes. Our laboratory is studying genetic mechanisms that promote increased blood pressure with the goal of identifying new opportunities for the prevention and treatment of hypertension, diabetes, and cardiovascular disease.

Pui-Yan Kwok, M.D., Ph.D. Professor In Residence Research Interests: Genetic analysis of complex traits, DNA technology development Summary: We are developing efficient methods to analyze single DNA molecules and applying molecular genetic tools to identify genetic factors associated with complex human traits such as longevity, sudden cardiac arrest, stroke, psoriasis, lupus, and kidney transplantation outcome. We are also conducting studies to identify genetic factors associated with drug response. The overall goal of our research is to develop the tools for genetic analysis of whole genomes and apply these tools to elucidate the genetic factors associated with common human diseases and phenotypes. The sequencing of the human genome and the mapping of common genetic variation by the International HapMap Consortium, in which our lab participated, have inspired an explosion of new technologies, accelerating identification of genetic susceptibility loci. Our phenotypes of interest include kidney transplantation outcomes, longevity, pharmacogenetics of membrane transporters, sudden cardiac death, psoriasis, skin cancer and brian vascular malformations and hemorrhage.

Robert W Mahley, B.S., Ph.D., M.D. Director Research Interests: I. Plasma lipoprotein metabolism ¥ Hepatic and intestinal origin of plasma lipoproteins; ¥ Apolipoprotein structure and function, especially apolipoprotein (apo) E and apoB; ¥ Characterization of cell surface receptors for lipoproteins; ¥ Role of the liver in cholesterol homeostasis. II. Relationship of plasma lipoproteins to the development and progression of atherosclerosis ¥ Role of diet in progression of coronary artery heart disease; ¥ Effect of apoE production in the artery wall on inhibition of atherogenesis. III. Role of apoE in the nervous system ¥ Effect on peripheral nerve injury and repair; ¥ Role in the pathogenesis of Alzheimer's disease; ¥ Effect on neuronal cytoskeleton. IV. Turkish Heart Study ¥ Director of epidemiological study to determine the risk factors responsible for coronary artery disease in Turkey; ¥ Characterization of genetic polymorphisms responsible for low HDL-C levels and metabolic syndrome in Turks; ¥ Co-director of physician continuing education program for Turkish doctors and medical students in the area of cardiovascular disease. Summary: My research has focused on the structure and function of apolipoprotein (apo) E, specifically its critical role in cholesterol homeostasis and atherosclerosis and, more recently, in Alzheimer's disease and neurodegeneration. ApoE regulates the clearance of plasma lipoproteins by mediating their binding to lipoprotein receptors and is also involved in peripheral nerve regeneration, lipid transport in the nervous system, and cytoskeletal stability and neurite extension and remodeling. A goal of our research is to develop a drug that will block the detrimental effects of apoE4 in cardiovascular and neurodegenerative disorders.

Mary J. Malloy, M.D. Senate Emeritus Research Interests: Molecular mechanisms in lipoprotein metabolism; genetic basis of metabolic disorders of lipoproteins and of arteriosclerosis Summary: My chief research foci are the discovery of previously unknown disorders that affect the metabolism of cholesterol and other lipids, and the discovery of genes that are associated with the risk of heart attack and stroke. Identification of these diseases and genetic markers of risk will lead to improved prevention and treatment of coronary disease and stroke.

Jeffrey E Olgin, M.D. Professor In Residence Research Interests: Cardiac Electrophysiology, Arrhythmias, Mechanisms, Remodeling, Cardiac Fibrosis, Atrial Fibrillation, Cardiac Ablation, Mouse models, animal models, mouse electrophysiology, optical mapping, atrial fibrillation ablation, clinical trials. Summary:

Steven D Rosen, Ph.D. Professor Research Interests: Sulfated Sugars in Biological Processes Summary: Sulfated Sugars in Biological Processes Glycoproteins on the outside of cells are modified by the addition of sulfate moieties to their sugars. These sulfated sugars serve significant roles in cell communication. We study how sulfated sugars function in the migration of white blood cells throughout the body and in the regulation of cancer cell growth.

Nelson B Schiller, M.D. Professor of Cardiology Research Interests: Dr. Schiller specializes in the use of echocardiography in the diagnosis and treatment of heart disease. His research interests center around the quantitation of left ventricular function by quantitative two-dimensional echocardiography and Doppler. Summary: Measuring the heart has been a preoccupation of civilizations since ancient Egypt. Measuring the heart using noninvasive techniques that are free of ionizing radiation has riveted the attention of modern medicine because knowledge of the size of the heart's anatomic parts provides powerful diagnostic and therapeutic information. Dr. Nelson B. Schiller a member of the Department of Medicine, Cardiology Division, CVRI and John J. Sampson-Lucie Stern Endowed Chair in Cardiology, has spent his career investigating the application of echocardiography to the precise measurement and clinical application of the volume, weight and hemodynamics of the chambers and valves of the heart. His work is currently centered on the Heart and Soul Study (Mary Whooley, MD PI), where echocardiography measurements are being related to outcomes of heart disease.

Arthur Weiss, M.D., Ph.D. Chief of Rheumatology Research Interests: Cell Surface Molecules and Molecular Events Involved in Lymphocyte Activation Summary: Dr. Weiss studies on how the functions of cells of the immune system are regulated. The immune system protects individuals from infections and malignancies. However, it is also involved in undesirable destructive responses, such as in autoimmune and allergic diseases as well as atherosclerosis and transplant rejection.

Ethan J Weiss, M.D. Research Interests: Coagulation, thrombosis, hemostasis, fibrinolysis, genetics, platelet, sexual dimorphism, sex hormone signaling. Summary: The blood clotting system is centrally important as a means to protect from blood loss. To do so, the system must be sensitive to disruptions in blood vessels. We know from naturally occurring human genetic mutations and experiments in animals that a deficiency of function or amount of clotting related proteins leads to bleeding. Yet the system must also be specific. There is an equal body of evidence that unregulated or increased propensity to form blood clots leads to deleterious clot formation such as occurs in heart attacks, strokes, and blood clots in large veins. The clotting system therefore must maintain exquisite balance between tendency toward clotting and tendency toward bleeding. Minor changes in concentration or function of a host of known and countless unknown proteins can tip the balance in either direction. Primarily, we use the mouse as a model system to define genetic regulation of blood clotting in an attempt to define genetic changes that might predispose to tipping the balance in either direction. We hope to learn more about the molecules and pathways that lead to clot formation. We hope to define novel molecules or pathways that regulate clotting or interact with known clotting pathways. We are particularly interested in how male or female sex affects clotting in animals. We know that women are 1) less likely to form clots in clotting tests and 2) are protected as compared to men in diseases associated with increased clotting like heart attacks. This tells us that women may have evolved a system with a more favorable balance between clotting and bleeding. We hope to learn how and why that may be. Ultimately, we hope to identify new risk factors for bleeding disorders as well as the clotting associated diseases such as heart attack and stroke. Furthermore, we hope that by understanding the biological mechanisms underlying such risks, we might eventually identify novel drug targets aimed at treating or preventing bleeding, stroke, heart attack or blood clots.

Prescott G Woodruff, M.D., M.P.H. Asst Professor In Residence Research Interests: Genomics, Asthma, Chronic Obstructive Pulmonary Disease, Stereology, Epidemiology, Clinical Trials, Medical Education Summary: My research relates to two common lung diseases, asthma and chronic obstructive pulmonary disease, and falls into three specific categories: 1) the identification of molecular sub-phenotypes of these diseases, 2) the elucidation of mechanisms of inflammation and remodeling in these diseases and 3) clinical trials of novel therapies.

William L Young, M.D. Professor/Vice Chair Research Interests: Integrative physiology of the cerebral circulation with special reference to cerebral vascular malformations and occlusive cerebrovascular disease; angiogenesis-related aspects of cerebral hemorrhagic disease; clinical physiology of systemic and cerebral circulatory manipulation during neuroanesthetic management Summary: Few effective therapies are available for stroke. Better understanding of how the formation of new blood vessels in a damaged brain contributes to recovery from injury is an important area of interest. An important subtype of stroke is rupture of abnormal blood vessels (arteriovenous malformations or aneurysms). Better understanding of how these diseases begin and progress will lead to more effective therapies.