CVRI Scientists

Vascular biology and atherothrombosis

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.

Israel F Charo, M.D. , Ph.D.
Professor In-Residence

Research Interests:
Structure and Function of Chemokine Receptors

Summary:
The goal of our research is to use gene targeting and creation of transgenic mice to study the in vivo functions of chemokines and chemokine receptors. Chemokines are proinflammatory cytokines that function in leukocyte chemoattraction and activation and block HIV–1 infection of target cells through interactions with chemokine receptors. In addition to their function in viral disease, chemokines have been implicated in the pathogenesis of atherosclerosis, glomerulonephritis, and inflammatory lung disease. The chemokine family is growing rapidly. Our laboratory focuses primarily on two chemokines: monocyte chemoattractant protein 1 (MCP-1) and fractalkine, a recently described and structurally unique chemokine.

Ajay Chawla, M.D., Ph.D
Professor

Research Interests:
Immune determinants of metabolism and regeneration; Nuclear receptor signaling in innate immune cells

Summary:
Across species, the aberrant activation of the innate immune system has been linked to pathogenesis of metabolic, inflammatory and degenerative diseases. However, the molecular pathways by which innate immune cells coordinate these diverse programs remain poorly understood. Our laboratory aims to elucidate the regulatory role of nuclear receptors and co-activator proteins in innate immune activation, and the importance of these pathways in paradigms of health and disease, such as obesity, diabetes, cancer and tissue regeneration.

Andrew J Connolly, M.D., Ph.D.
Professor of Clin. Pathology

Research Interests:
Basic and translational research in cardiovascular and pulmonary pathology

Summary:
The goal of our research is to explore pathology of the heart, blood vessels, and lungs, using both patient materials and animal models. This includes the heart muscle disorders underlying heart failure, thrombotic occlusion of blood vessels, diseases of the aorta, and lung cancer models.

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.

Shaun R Coughlin, M.D., Ph.D.
Professor

Research Interests:
Signaling mechanisms in cardiovascular biology and disease, thrombin signaling

Summary:
My laboratory seeks to define signaling mechanisms that govern cardiovascular biology and disease, with a focus on G protein-coupled receptors (GPCRs). We discovered and characterized protease-activated receptors (PARs), a family of GPCRs that permit thrombin and related proteases to regulate the behavior of platelets and other cells. Together with the coagulation cascade, these receptors link tissue injury to cellular responses that regulate blood clotting, inflammation, pain sensation, and perhaps cytoprotection and repair. PARs are necessary for platelet activation by thrombin, and a PAR1 antagonist was recently shown to prevent myocardial infarction and ischemic stroke in patients with known atherothrombotic disease, albeit at the cost of increased bleeding. Current work focuses on better defining the roles and interactions of coagulation factors, PARs and other regulators of hemostasis and thrombosis in mouse and zebrafish models. Additionally, in collaboration with Brian Kobilka, we seek to solve crystal structures of PAR1 off and on states to more fully understand PAR pharmacology and the "tethered ligand" activation mechanism we postulated for these receptors.

PARs also contribute to embryonic development. PAR function in endothelial cells is necessary for normal hemostasis, blood vessel remodeling and/or integrity in midgestation mouse embryos. PAR signaling in surface ectoderm appears to be necessary for neural tube closure; recent findings suggest involvement of local membrane-tethered proteases that regulate epithelial structure and function in part via PARs. Current work utilizes zebrafish and mouse models to identify the molecular and cellular mechanisms underlying these phenomena.

The role of sphingosine-1-phosphate (S1P) signaling via S1P1 and related GPCRs in regulation of vascular permeability is another focus. We found that S1P in the plasma compartment is important for normal vascular permeability/integrity in the adult mouse; current work seeks to determine whether S1P's acting directly on endothelial cell S1P1 mediates this effect and, if so, whether such signaling plays a tonic maintenance function and/or triggers a dynamic response to vascular leak. A second area of focus reflects an unexpected finding made in S1P1 morphant zebrafish embryos generated to better define the roles of S1P1 in the vasculature: S1P1 is necessary for normal sarcomere formation in the developing zebrafish heart. Ongoing work focuses on defining the mechanisms involved and determining whether this system also functions in mammals.

William F Degrado, Ph.D.
Professor

Research Interests:
De novo protein design, drug design, protein structure/function, membrane protein structure, integrins, antivirals, antibiotics.

Summary:
DeGrado's group works on the design of molecules that inform our understanding of biological processes. They also have developed small molecules drugs for various as potential pharmaceuticals, including antithrombotics, heparin reversal agents, antibacterials, and antiviral agents.

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.

Peter Ganz, M.D.
Chief, Cardiology/SFGH

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.

Stanton A Glantz, Ph.D.
Professor of Medicine

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.

Akiko Hata, Ph.D.
Professor

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.

Guo Huang, Ph.D.
Assistant Prof in Residence

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.

Natalia Z Jura, PhD
Assistant Professor

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

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

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.

Dengke Ma, Ph.D.
Assistant Professor

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.

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.

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.

Michael A Matthay, M.D.
Professor In Residence

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.

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

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.

Takashi Mikawa, M.S., Ph.D.
Professor

Research Interests:
Morphogenesis, development, body axis, patterning, cell-to-cell communication, cell architecture, cell fate diversification, cardiovascular system, cardiac conduction system, central nervous system, haemodynamics, growth factor signaling.

Summary:
The establishment of extremely complicated structures and functions of our organ systems depends upon orchestrated differentiation and integration of multiple cell types. Our group focuses to explore a common developmental plan for successful organogenesis, by investigating the mechanisms involved in the differentiation and patterning of the cardiovascular and central nervous systems.

Peter E Oishi, M.D.
Assistant Professor in Residence

Research Interests:
Pulmonary vascular disease, endothelial function, congenital heart disease, pulmonary venous stenosis.

Summary:
Pulmonary vascular endothelial function under conditions of abnormal pulmonary blood flow, secondary to congenital cardiac defects.

A significant number of infants and children born with heart defects are also at risk for developing problems with the blood vessels of the lung (pulmonary vascular disease). Our research is focused on exploring the mechanisms that link the abnormal blood flow patterns that accompany many of these common heart defects with the development of pulmonary vascular disease. In order to study these mechanisms our laboratory uses animal models of various cardiac defects that allow an integrated approach for studying the accompanying physiologic, biochemical, molecular, and cellular derangements. Our hope is that by elucidating the controlling mechanisms, new therapies and treatment strategies can be devised that will improve the outcome for these children.

Paul C Simpson, M.D.
Prof In Rsdn

Research Interests:
Molecular & cellular mechanisms of myocardial hypertrophy and heart failure Adrenergic receptors, signaling, and drug development

Summary:
Dr. Simpson is working to develop new drugs to treat heart failure, one of the most common causes of hospitalization and death in the USA and Western World. He has recently identified a promising drug target, alpha-1-adrenergic receptors, and is working to translate this into clinical use.

Matthew L Springer, Ph.D.
Professor In Residence

Research Interests:
Angiogenesis, VEGF, stem cells, progenitor cells, gene therapy, heart failure, myocardial infarction, coronary artery disease, cardiac regeneration, peripheral artery disease, vascular injury, nitric oxide, flavanols, skeletal muscle myoblasts, secondhand smoke

Summary:
Our research interests include cell therapy and gene therapy approaches to studying cardiovascular disease, with the goals of exploring potential treatments and understanding underlying mechanisms involved in angiogenesis, vascular function, and treatments for myocardial infarction. We are studying the effects of VEGF and pleiotrophin gene therapy on the heart and limb vasculature in mice. Further interests center in the therapeutic effects of ultrasound-guided bone marrow cell implantation into the heart after myocardial infarction, with a special emphasis on the therapeutic implications of the age and cardiac disease state of the cell donor. Similarly, we are studying the effects of age and disease on circulating angiogenic cells (sometimes called endothelial progenitor cells), with a focus on the roles of endothelial nitric oxide synthase and nitric oxide in the function of these cells. Lastly, we have developed a rat model of endothelium-dependent flow-mediated vasodilation, and are using it to examine mechanisms underlying vascular reactivity and how they are affected by tobacco and marijuana secondhand smoke exposure.

Rong Wang, Ph.D.
Professor

Research Interests:
Molecular Regulation of Mammalian Arterial Venous Specification

Summary:
Research in my lab is focused on angiogenesis, or new blood vessel formation, which is a critical process in development and disease. My lab aims to advance the fundamental understanding of the cellular, molecular, and hemodynamic mechanisms underlying arterial-venous programming in normal and pathological angiogenesis. We use cutting-edge mouse genetics to delete or express genes in a cell lineage-specific and temporally controllable fashion in endothelial cells. This advance is crucial for the study of candidate genes in vascular function, especially when combined with sophisticated 5D two-photon imaging (3D + blood flow over time). These innovative approaches provide us with exceptional access to gene function in both healthy and pathological conditions in living animals. This basic approach is complemented by preclinical studies with patient samples in addition to our mouse models of disease. In particular, we investigate the molecular regulators governing arterial-venous programming - particularly the Notch, ephrin-B2, and TGF-beta signaling pathways - in both normal and pathological conditions. Ongoing projects: Vascular Development. Our lab aims to identify molecular regulators of arterial and venous cell fate determination and morphogenesis in embryonic development. We primarily focus on the origin and morphogenesis of the dorsal aorta and cardinal vein, the first major artery-vein pair to form in the body. Arteriovenous Malformation (AVM). AVMs are severe vascular anomalies that shunt blood directly from arteries to veins, displace intervening capillaries, and bypass tissues. My lab studies the pathogenesis and regression of AVMs. We have a long history of investigation using animal models into Notch-mediated AVM pathogenesis as well as into potential treatments for the disease.

Arterial occlusive diseases and arteriogenesis. The body responds to arterial occlusions by inducing arteriogenesis, or radial enlargement of arteries, to restore circulation to blood-deprived tissue. We are investigating pro-arteriogenic molecular regulators to uncover potential therapeutic targets, which may be used to enhance the body's natural defense against arterial occlusive disease.

Cancer. Solid tumors induce arteriogenesis to support their growth. We investigate the molecular stimulators of arteriogenesis in tumor progression and regression, particularly in hepatocellular carcinoma (HCC), which is characterized by large and highly arterialized tumor masses in the liver. We study genes regulating tumor arterial growth and modify these genes to target tumor arterial supply and to inhibit HCC growth.

Ultimately, through these distinct but interconnected fields of study, we hope to identify novel drug targets and inform rational design of new therapeutics to treat human disease.

Lei Wang, Ph.D.
Associate Professor

Research Interests:
Design and encode novel amino acids to study biological processes and to develop new biotherapeutics.

Summary:
We build proteins in living cells using new amino acids. By harnessing the novel properties of these new building blocks, we probe biological processes in their natural settings and engineer unique biomolecules to understand mechanisms of cellular function and to develop new treatments of diseases.

Orion D Weiner, Ph.D.
Professor

Research Interests:
Cell polarity, chemotaxis, actin cytoskeleton, cell signaling, cell migration, microscopy, biochemistry, neutrophils, systems biology, self-organization, inflammation, Rac, PI3Kinase, WAVE complex.

Summary:
Proper movement in response to cues from the outside world is as important for single cells as it is for drivers on a busy highway. If cues are misinterpreted or the movement goes awry, terrible accidents ensue, the delicate wiring of the nervous system fails, single-celled organisms can`t hunt or mate, the immune system ceases to function properly, and cancer cells spread from one part of the body to another. How do single cells, without the benefit of a brain, interpret the subtle micro-world of attractants and repellents to decide where to go? Our research focuses on dissecting the inner workings of the cellular "compass" used to guide cells on their journey. Because the core of the compass has been conserved over more than a billion years of evolution, we have been able to combine discoveries from yeast to humans to glimpse some rough outlines of the underlying machinery. However, many of the important connections are still missing. Our research focuses on identifying these key missing components and how they are wired together to process information with the hope that we can eventually make cells move when (and where) we want them to and stop them when we don`t.

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.
Associate Professor

Research Interests:
Coagulation, thrombosis, hemostasis, fibrinolysis, genetics, platelet, sexual dimorphism, growth hormone signaling, fatty liver disease, regulation of energy metabolism and obesity

Summary:
Our group has two main interests. The first is to understand the mechanisms underlying the regulation of energy metabolism by growth hormone. Growth hormone is well-known to promote lipolysis as a means of mobilizing energy from stores in the form of free fatty acids. To accommodate tissues and organs with increased energy needs, fatty acid uptake is also regulated by growth hormone. The precise molecular mechanisms driving these two processes remain unclear. With an aim toward understanding mechanisms of obesity and related conditions, we use a molecular and cellular approach combined with mouse genetic models to understand how growth hormone regulates lipolysis and the uptake of fatty acid by cells and tissues.

Our second interest is in defining novel mechanisms of thrombosis susceptibility. Our group has had a long interest in thrombosis. Recently, we have focused on understanding ways to modulate thrombosis risk without increasing the risk of bleeding. Here, we also use molecular, cellular, and mouse genetics approaches.

Zena Werb, Ph.D.
Professor and Vice Chair

Research Interests:
Extracellular communication in development and disease

Summary:
The cellular microenvironment provides cells with information essential for controling development , cell-specific fate determination, gain or loss of tissue-specific functions, cell migrations, tissue repair and cell death. We are studying the role of the microenvironment in controlling embryonic development, mammary gland and bone development and tumorigenesis. Our interests include the critical roles that the ECM, inflammatoryand innate immune cells, vascular development and angiogenesis and degradative enzymes such as the matrix metalloproteinases play in these processes. We are taking genetic and molecular approaches to determine the identity and function of the critical molecules, how their expression and activities are regulated, what the molecular and cellular targets of these genes are, and how these regulate the signaling pathways. We are studying how a developing vascular system regulates bone formation, breast development and tumor growth. For example, we have found that tumor cells metastasize in regions of the tumor where blood vessels are abnormal and where there are abundant inflammatory cells. We want to understand the temporal, spatial and causal relationship between these three compartments, and whether targeting the tumors cells, blood vessels or the inflammatory cells, or all of them can slow down metastasis.

Yerem Yeghiazarians, M.D.
Associate Professor

Research Interests:
Stem cell (adult or embryonic), Myocardial infarction, Heart failure, Cardiomyopathy

Summary:
The goal of the UCSF Translational Cardiac Stem Cell Program is to bring recent advances in basic science and biology of stem cells to patients with heart disease, heart failure, and cardiomyopathy. There are many different types of stem cells. These can be broadly categorized as adult stem cells (derived from the patient) vs. embryonic type of stem cells. Our group is interested in studying which type of stem cell(s) would be most useful as novel therapy in patients after a heart attack, and exploring the mechanisms by which stem cells can potentially improve the cardiac function.

Ann C Zovein, M.D,
Assistant Professor

Research Interests:
Vascular development, diversity of endothelial lineages, vascular contributions to stem cell niches including hematopoietic stem cell emergence

Summary:
While at first glance it may appear that the blood vessels throughout the body have similar properties and functions, on closer examination vessels that comprise diverse vascular beds may arise from distinct origins and have unique potential and pathology. We investigate, from a developmental perspective, what makes arterial endothelial subsets unique… is it their location? or developmental history? And do these properties predict their future? i.e. propensity for disease.

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