Category: Vascular Biology and Atherothrombosis

Donald M McDonald, M.D., Ph.D.

Research Interests:
Angiogenesis; cancer; chronic inflammation; endothelial cells; vascular remodeling

Summary:
Our laboratory is studying the cellular mechanisms of angiogenesis, vascular remodeling, and plasma leakage in mouse models of chronic inflammation and cancer. We are also studying cellular changes in lymphatic vessels in disease models. The goal is use novel in vivo cell biological approaches to identify abnormalities of blood and lymphatic vasculature that can serve as the basis of novel treatments. In one area of research, we are examining the mechanism of the action of VEGF, angiopoietins, and other factors on blood vessel growth, remodeling, and leakiness. Other experiments include exploring the mechanism and reversibility of vascular remodeling and angiogenesis and examining the cellular actions of inhibitors of angiogenesis and lymphangiogenesis in tumors and inflammatory disease. We are also studying the cellular mechanisms of plasma leakage in disease. Here, the mechanism of plasma leakage from tumor vessels, due to a defective endothelial monolayer, contrasts with leakage in inflammation, where intercellular gaps form in seconds and reseal spontaneously. Multiple different disease models in wild-type, transgenic, and knockout mice are being used in combination with novel therapeutic agents to identify the cells and growth factors that drive angiogenesis and vascular remodeling and to understand the mechanism of reversibility of vascular changes in inflammation and cancer.

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Michael A Matthay, M.D.

Research Interests:
Alveolar epithelial transport under normal and pathologic conditions. Resolution of pulmonary edema Mechanisms of Acute Lung Injury

Summary:
My research program is focused on identifying mechanisms responsible for fluid transport across the alveolar epithelium using cell, molecular, and in vivo models. In addition, our group is focused on understanding the mechanisms responsible for the development and resolution of pulmonary edema and acute lung injury in critically ill patients with acute respiratory failure. The studies include experimental and human-based studies designed to understand the pathogenesis of acute respiratory failure and to test potential new therapies. The work is supported primarily by grants from the National Heart, Lung, and Blood Institute.

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Michael J Mann, M.D.

Research Interests:
1. Molecular/cellular biology and molecular genetics of atherosclerosis and heart failure. 2. Development of hybrid surgical and molecular/cellular therapies for heart disease. 3. Stem and progenitor cell transplantation for cardiovascular regeneration. 4. Cardiovascular tissue engineering. 5. Reduction to clinical practice of current methods in genetic, molecular and cellular disease intervention. 6. Novel targeted molecular therapies for lung cancer. 7. Molecular profiling of cancers for personalized medicine. 8. Development of novel methods of in vivo/ex vivo gene therapy and gene transfer. 9. Novel approaches to therapeutic neovascularization for coronary and peripheral ischemic disease. 10. Cardiovascular cell cycle biology. 11. Myocardial gene therapy.

Summary:
Dr. Mann’s research focuses on the molecular and cellular biology of heart disease with an emphasis on practical ways to develop new treatments for heart failure. These involve potential gene and molecular therapies, combinations of molecular and cell-based treatments with surgical reconstruction, and evaluation of novel materials for the development of bioartificial replacements of lost or damaged heart tissue.

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Robert W Mahley, B.S., Ph.D., M.D.

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.

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Dengke Ma, Ph.D.

Research Interests:

Genetic approaches to understanding physiology and diseases, oxygen-modulated metabolism and behavior; brain-heart-lung interaction and interoception; ischemic disease and tolerance; novel genes and pathways evolutionarily conserved in C. elegans and humans.

Summary:
As humans, we drink when thirsty, eat when hungry, and increase our breathing and heart rates when short of oxygen. How do we (our bodies) know when and how to respond to changes in internal bodily states (e.g. loss of nutrient or oxygen)? Genes and traits that facilitate such underlying mechanisms confer great advantages for animal survival and are strongly selected for during evolution. Using both C. elegans and tractable mammalian model systems, we seek to understand the molecular, cellular and neural circuit basis of how animals sense and respond to changes in internal metabolic and energetic states to elicit behavior and maintain homeostasis. Dysfunction of these fundamental physiological processes leads to many disorders, including obesity, diabetes, neurological and cardiovascular diseases.

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John P Kane, M.S., M.D., Ph.D.

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.

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Natalia Z Jura, PhD

Research Interests:
Receptor tyrosine kinases, kinase regulatory mechanisms, membrane proteins, feedback regulation of cell signaling

Summary:
We study basic mechanisms of cellular signaling by Receptor Tyrosine Kinases with a goal to understand how cells receive and process growth signals provided by the neighboring cells and the extracellular milieu. Receptor Tyrosine Kinases are single pass transmembrane receptors that catalyze tyrosine phosphorylation upon activation of their intracellular kinase domains. These receptors are principal regulators of growth and survival signals in cells and therefore frequently become deregulated in human diseases. We are interested in understanding how the kinase activity of these receptors is regulated by ligand binding and how the receptors associate with their regulatory components during the activation process. By combining biochemistry and cell biology we are studying these processes in the reconstituted membrane systems in vitro and in the plasma membrane of the living cells. We also use crystallography to gain an atomic resolution insight into Receptor Tyrosine Kinase regulation that will help us design new approaches for therapeutic intervention.

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Jura Lab Website

Guo Huang, Ph.D.

Research Interests:
Comparative study of heart development and regeneration, ischemic heart diseases, stem cell, cardiomyocyte proliferation, regenerative biology

Summary:
The ability to regenerate damaged or lost tissues varies dramatically across organisms and developmental stages. For example, heart regeneration is robust in adult zebrafish and newborn mouse while very limited in adult mouse and human. This presents a particular problem for patients with a heart attack who suffer from a significant loss of heart muscle cells and subsequent life-threatening functional deterioration of the heart.

By taking a comparative approach to study regenerative versus non-regenerative heart repair processes in zebrafish and mouse, we seek to uncover ancestrally conserved injury responses and more importantly, to identify the signals blocking regeneration in the mammalian heart and consequently new treatment strategies for heart diseases.

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Website

Akiko Hata, Ph.D.

Research Interests:
Mechanisms of growth factor signaling in the control of cell growth and differentiation of vascular cells

Summary:
Research in the Hata lab focuses on the role of the BMP/TGF signaling pathway in the maintenance of vascular homeostasis, control of vascular injury repair, and pathogenesis of vascular diseases, including idiopathic pulmonary arterial hypertension (IPAH), hereditary hemorrhagic telangiectasia (HHT), restenosis, and atherosclerosis. Our approach is to study gene mutations identified among patients with IPAH or HHT and elucidate how these gene products affect the signaling pathway as well as vascular physiology using both cell culture and animal models.

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Stanton A Glantz, Ph.D.

Research Interests:
Mechanics of cardiac function (experimental and theoretical); environmental tobacco smoke and tobacco control policy

Summary:
Dr Glantz studies the effectiveness of different tobacco control strategies, particularly in the context of large state-run tobacco control programs, how the tobacco industry works to systematically distort the scientific process and animal and human studies of the effects of passive smoking on the heart.

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Peter Ganz, M.D.

Research Interests:
Human endothelial biology, inflammation in cardiovascular diseases, statins, cardiovascular disease in rheumatoid arthritis, cardiovascular disease in HIV, cardiovascular effects of smoking and second hand smoke, cardiovascular effects of air pollutants.

Summary:
Dr. Ganz’ research interests have focused on the role of endothelial dysfunction and inflammation in cardiovascular disease in human subjects. In health, endothelium (the cell lining the inside of arteries), protects against diseases of blood vessels such as atherosclerosis (blockages in arteries). In the presence of damaging risk factors (for example, too much bad cholesterol, not enough good cholesterol, smoking, diabetes or high blood pressure), the endothelium becomes injured and promotes rather than retards cardiovascular disease. The same damaging risk factors also stimulate inflammation in the wall of human arteries. Inflammation and endothelial dysfunction lead to heart attacks and deaths from heart disease; thus, Dr. Ganz is currently focused on finding treatments to reverse endothelial dysfunction and reduce inflammation and their harmful effects and thereby prevent cardiovascular disease in patients.

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Jeffrey R Fineman, M.D.

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.

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