Allen, Christopher D
Ashrafi, Kaveh
Atabai, Kamran
Black, Brian L
Blanc, Paul D
Botvinick, Elias H
Boushey, Homer A
Broaddus, V Courtney
Brown, James K
Bruneau, Benoit G
Calfee, Carolyn S.
Caughey, George H
Chang, Andy
Chapman, Harold A
Charo, Israel F
Chawla, Ajay
Chuang, Pao-Tien
Clyman, Ronald I
Conklin, Bruce R
Connolly, Andrew J
Conte, Michael S
Coughlin, Shaun R
Degrado, William F
Deo, Rahul C
Derynck, Rik M
Dobbs, Leland G
Engel, Joanne N
Erle, David J
Fahy, John Vincent
Fineman, Jeffrey R
Ganz, Peter
Gardner, David G
Gartner, Zev Jordan
Glantz, Stanton A
Gold, Warren M
Grabe, Michael D
Gropper, Michael
Grossman, William
Hart, Daniel O
Hata, Akiko
Hawgood, Samuel
Hoffman, Julien I
Huang, Guo
Ingraham, Holly A
Irannejad, Roshanak
Jan, Lily Y
Julius, David J
Jura, Natalia Z
Kan, Yuet W
Kane, John P
Karliner, Joel S
Kornberg, Thomas B
Koth, Laura L
Krauss, Ronald M
Kurtz, Theodore W
Kwok, Pui-Yan
Lazarus, Stephen C
Lee, Randall J
Lim, Wendell A
Ma, Dengke
Mahley, Robert W
Malloy, Mary J.
Mann, Michael J
Matthay, Michael A
Mcdonald, Donald M
Mikawa, Takashi
Minor, Daniel L
Mostov, Keith E
Oishi, Peter E
Olgin, Jeffrey E
Pearce, David
Peng, Tien
Raleigh, David R
Redberg, Rita F
Reiter, Jeremy F.
Rock, Jason R.
Rowitch, David H
Scheinman, Melvin M
Schiller, Nelson B
Seiple, Ian Bass
Sheppard, Dean
Shokat, Kevan M
Shu, Xiaokun
Shum, Anthony K
Simpson, Paul C
Springer, Matthew L
Srivastava, Deepak
Teitel, David F
Vedantham, Vasanth
Von Zastrow, Mark E
Wang, Rong
Wang, Biao
Wang, Lei
Weiner, Orion D
Weiss, Arthur
Weiss, Ethan J
Werb, Zena
Woodruff, Prescott G
Xu, Allison Wanting
Yeghiazarians, Yerem
Zovein, Ann C

CVRI Scientists

Advanced technologies

Christopher D Allen, Ph.D.
Assistant Professor

Research Interests:
Cellular dynamics of allergic immune responses underlying asthma

Summary:
Asthma is a chronic lung disease that afflicts tens of millions of people in the US and is particularly prevalent in children. In the majority of individuals with asthma, underlying allergic inflammation in the lung makes a significant contribution to the disease etiology. In order to understand the cellular and molecular events driving this allergic inflammation, we use advanced technologies, including two-photon microscopy and flow cytometry, to directly visualize and characterize inflammatory cells in the lungs as well as in lymphoid organs that 'prime' cells for immune responses in the respiratory tract. A particular emphasis of our research is on the generation and function of the IgE class of antibodies that contribute to allergic responses.

Kaveh Ashrafi, Ph.D.
Associate Professor

Research Interests:
Genetics of fat regulation and neurobiology of feeding behavior

Summary:
Obesity is a major risk factor associated with many diseases including diabetes, cardiovascular and gastrointestinal diseases, arthritis, and certain forms of cancers. The prevalence of obesity reflects the combination of high calorie diets with sedentary lifestyles. However, genetic predispositions play profound roles in determination of an individual's fat. How genetic and environmental factor interact to determine fat content and how excess fat accumulation causes disease processes are poorly understood. To identify genes that underlie fat regulation we use the genetically tractable worm C. elegans. This system has allowed us to discover novel fat regulatory pathways, compounds that alter fat content, and probe the neural circuits that regulate fat and feeding.

Kamran Atabai, M.D.
Assistant Professor

Research Interests:
Apoptotic cell and collagen clearance in health and disease.

Summary:
The accumulation of cellular and molecular debris in the extracellular compartment must be precisely regulated to preserve tissue integrity. We are interested in discovering the pathways that regulate tissue homeostasis through the removal of matrix molecules (collagen) and cellular debris (apoptotic cells) under normal and pathological conditions.

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.

Paul D Blanc, M.D., MSPH
Division Chief

Research Interests:
Epidemiology of occupational lung disease, Asthma outcomes and Occupational toxicology

Summary:
Dr. Blanc's research addresses the impact of work-related and environmental exposures on human health, in particular respiratory diseases such as asthma, and COPD. His work focuses on the role that such exposures can play in causing disease and also how ongoing stressors can aggravate pre-existing disease and lead to disability

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.

Homer A Boushey, M.D.
Professor

Research Interests:
Bronchial hyperreactivity in asthma. Effects of viral infection on airway function. Regulation of airway mucous secretion and vascular permeability.

Summary:
Dr. Boushey's goal is to develop ways of curing and preventing asthma. His research takes advantage of new methods for detecting viruses and bacteria to examine relationships among the allergens and bacteria found in the environment, bacteria in the gastrointestinal tract, the function of the immune system, and the development of asthma.

V Courtney Broaddus, M.D.
Professor

Research Interests:
Role of apoptosis in asbestos-induced malignancy. Molecular interaction of asbestos fibers with mesothelial cells, specifically with regard to the role of cell surface adhesion receptors.

Summary:
Our lab studies the ways that tumor cells resist dying either when they are single cells or when they aggregate into clumps, called 3-dimensional spheroids. Our goal is to understand the strategies that resistant tumors use to avoid death and then find ways to bypass these defenses.

James K Brown, M.D.
Professor

Research Interests:
Protease signaling

Summary:
In asthma, abnormal growth of airway smooth muscle cells contributes to difficult breathing. Mast cells are a prominent inflammatory cell in the airways of these patients, and during allergic reactions, mast cells release a substance called tryptase. Our work focuses on understanding how tryptase activates smooth muscle cells to grow.

Benoit G Bruneau, B.Sc., Ph.D.
Associate Professor

Research Interests:
Heart development, congenital heart disease, chromatin, embryogenesis, transcription

Summary:
Our laboratory studies the genes that direct a cell to become a heart cell, focusing on the machinery within each cell that turns genes on or off. Many of these factors are implicated in human congenital heart disease, and our studies also focus on understanding the basis of these diseases.

Carolyn S. Calfee, M.D., MAS
Associate Professor

Research Interests:
Acute lung injury, acute respiratory distress syndrome, cigarette smoking, molecular epidemiology, biomarkers

Summary:
Dr. Calfee's primary academic focus is the prevention, diagnosis, prognosis, and treatment of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). Current research projects include: (1) the role of biomarkers in investigating ALI/ARDS pathogenesis, early diagnosis, treatment, and prognosis; (2) the role of cigarette smoke exposure in susceptibility to lung injury; and (3) novel treatments for acute lung injury.

George H Caughey, M.D.
Professor In Residence

Research Interests:
Regulation of lung and airway function by mast cell, leukocyte and epithelial proteases

Summary:
The Caughey lab is interested in understanding how protein-cleaving enzymes of mast cells, white blood cells, and cells lining the airway contribute to inflammation, host defense, tissue remodeling and barrier function in the lung. These studies relate to clinical problems in asthma, cystic fibrosis, lung transplantation and pneumonia.

Andy Chang, Ph.D.
Assistant Professor

Research Interests:
Acute oxygen and metabolic sensing in cardiopulmonary regulation and disease

Summary:
To maintain optimal oxygen delivery to tissues, there is constant regulation of respiratory and cardiovascular systems by mechanisms that act on different time scales. On a fast time scale, a small chemosensory organ called the carotid body senses decreases in blood oxygen to increase breathing within seconds. The carotid body can also regulate cardiovascular function acutely, and carotid body hyperactivity contributes to disease progression in hypertension, heart failure, and metabolic syndrome. Using the mouse as our primary model, we aim to identify the molecular mechanisms that mediate the carotid body's ability to detect changes in blood oxygen as well as other metabolic signals, such as carbon dioxide and acid. One long term goal is to apply this knowledge to manipulating carotid body activity in the treatment of cardiovascular disease and metabolic syndrome.

Harold A Chapman, M.D.
Professor

Research Interests:
Antigen presentation by MHC class II molecules important to immunity and autoimmunity and extracellular matrix remodeling important to cell migration and tissue repair

Summary:
The Chapman lab is focused on basic and biomedical aspects of lung injury and tissue remodeling. Currently the lab is exploring the process of epithelial to mesenchymal transition (EMT) in the lung, a process whereby epithelial lining cells of the lung become reprogrammed to migrate and activate a fibrotic program. The process is also implicated in progression of lung cancer and the lab is exploring the mechanisms by which EMT contributes to lung fibrosis and cancer metastasis.

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.

Pao-Tien Chuang, M.D. , Ph.D.
Professor

Research Interests:
Cell-cell signaling during mammalian development and in postnatal physiology

Summary:
We use mouse as a model system to understand how embryos develop. This knowledge is critical for understanding the basis of human congenital defects. Moreover, many adult diseases have their origin in development. Thus, our studies have important implications for developing stem cell therapy and identifying the cause of cancers.

Ronald I Clyman, M.D.
Prof In Rsdn Ped & CVRI

Research Interests:
Cardiology, Cell Biology, Developmental Biology, Neonatology, Neonatal Cardiology

Summary:
The ductus arteriosus is a vital fetal blood vessel that diverts blood away from the fetus's lungs and towards the placenta during life inside the uterus. After birth it is essential that the ductus arteriosus constricts and obliterates itself so that the normal postnatal pattern of blood flow can be established. Essentially all full term infants will have closed their ductus by the third day after birth. Preterm infants of less than 30 weeks gestation have a high chance of having a persistently open or patent ductus arteriosus (PDA). If the ductus arteriosus remains open it contributes to the development of several neonatal morbidities: prolonged ventilator dependency, pulmonary hemorrhage, pulmonary edema, chronic lung disease and necrotizing enterocolitis. Our laboratory has been studying the factors that regulate normal closure of the ductus arteriosus in full term infants and abnormal persistent ductal patency in preterm infants. Approaches used to study this problem are: controlled clinical trials, integrated whole animal physiology, in vitro organ culture, and cell biology

Bruce R Conklin, M.D.
Professor In Residence

Research Interests:
Engineering Hormone Signaling Pathways In Vivo

Summary:
Hormone receptors direct the development and function of complex tissues, including those found in the cardiovascular system. The focus of our research is on the largest known family of receptors for hormones and drugs, the G protein–coupled receptors. We combine genetic engineering, stem cells and new computer programs to find new treatments of cardiovascular disease.

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.

Rahul C Deo, M.D., Ph.D.
Assistant Professor

Research Interests:
Genetic variants underlying cardiovascular and metabolic disease

Summary:
We are now surrounded by an unprecedented amount of information about the human genetic variation that influences who will develop cardiovascular disease. Although more variants are likely to be found, we can now turn our attention to deciphering the mechanisms by which this variation in DNA ultimately governs the differences from individual to individual. My research is focused on tackling this problem in several ways, combining experimental and emerging computational approaches to take advantage of the enormous amount of new molecular information in the public domain. Specifically, I hope to adapt the sorts of statistical learning tools used in finance and engineering (and consumer marketing!) to narrow the list of likely genes that determine our cholesterol levels. Guided by this information, I hope to move to the experimental laboratory to then decipher how individual variation affects the amount of these genes, and to break down how common environmental exposures influence their levels. My ultimate aim is to identify potential new drug targets and develop new means to classify patients according to their "molecular fingerprints" under stress.

Rik M Derynck, Ph.D.
Professor

Research Interests:
Transmembrane TGF-a and TGF-b receptor signaling in cell proliferation and differentiation.

Summary:
Dr. Derynck studies signaling mechanisms that regulate the generation of bone, muscle and fat cells and how these cells derive from mesenchymal stem cells. This knowledge is used to direct mesenchymal stem cells and pre-adipocytes toward the generation of bone and muscle tissues.

Leland G Dobbs, M.D.
Adjunct Professor

Research Interests:
Pulmonary alveolar epithelial development and response to injury, development of biomarkers for the measurement of lung injury

Summary:
Our laboratory studies the pulmonary alveolar epithelium. More than 99% of the large internal surface area of the lung (in humans ~100-150 m2) is lined by the alveolar epithelium, which is comprised of type I and type II cells, both of which are thought to be essential for mammalian life. Type I cells are very large squamous cells that cover more than 98% of the internal surface area of the lung, providing a narrow anatomic barrier between the air and blood compartments critical for efficient gas exchange. Type II cells are small cuboidal cells characterized by morphologically distinct secretory organelles, lamellar bodies, which contain the intracellular storage pool of pulmonary surfactant. In vivo, type II cells have the capacity to repair injured alveoli, acquiring at least some characteristics of the type I cell phenotype; under these conditions, they appear to transdifferentiate. Current accepted paradigms are that type I cells play a minimal functional role in the lung, but that type II cells perform major alveolar epithelial functions, including acting as progenitor cells during development and after injury. These paradigms do not adequately explain the results of recent experiments in our laboratory. We have developed novel methods for isolating and studying type I cells, which have previously have been resistant to study. Experiments with both in vitro and in vivo models suggest both a major role for the type I cell in ion and fluid transport and revised paradigms for both alveolar epithelial development and response to injury.

Joanne N Engel, M.D., Ph.D.
Prof In Residence

Research Interests:
Bacterial Pathogen-Host Cell Interactions

Summary:
My laboratory is interested understanding and exploiting the complex interplay of microbial pathogens with eukaryotic cells. To that end, we have investigated the key processes of microbial attachment and entry, intracellular survival, and host cell injury in the context of two important human pathogens, Pseudomonas aeruginosa (PA) and Chlamydia trachomatis (CT). Each of these microorganisms has developed a unique strategy for successful survival that involves subverting and exploiting host cell pathways. Dissecting these processes will allow the development of new diagnostics, therapeutics, and vaccines and will provide a unique window into eukaryotic cell biology.

David J Erle, M.D.
Professor of Medicine In Resid

Research Interests:
Asthma, allergy and inflammation; functional genomics

Summary:
Asthma is an increasingly common disease that affects about 20 million American children and adults. We are working to understand how proteins made by the immune system act within the lungs to cause some of the most important problems experienced by people with asthma. We also work on understanding newly discovered ways in which genes are turned on and off during health and disease.

John Vincent Fahy, M.D.
Professor In Residence

Research Interests:
Mechanism oriented studies of airway disease in human subjects

Summary:
Our research involves studies in people with airway diseases such as asthma, cystic fibrosis, and chronic bronchitis. We are involved in clinical trials of new and established treatments on the one hand and in clinical studies designed to improve understanding of mechanism of disease on the other. For clinical trials, we often collaborate with other CVRI investigators or investigators at other institutions to compare the efficacy of new and established drugs. In conducting clinical trials, we are usually interested in exploring the effects of drugs not just on measures of lung function but also on measures of airway inflammation and remodeling. For this purpose, our laboratory has developed expertise in measuring markers of inflammation and remodeling in samples of sputum or in samples of airway fluids and tissue collected during bronchoscopy. Our lab is particularly experienced in measuring gene expression using gene chips and PCR and in quantifying pathology using a rigorous method of quantitative morphology called stereology.

For our research on mechanisms of airway disease, we are particularly interested in abnormalities of airway epithelial cells (the lining cells of the airway) and in abnormalities in airway mucus. Mucus abnormalities are common in lung diseases, and we are interested in finding out the specific mucus abnormalities that are characteristic of different lung diseases such as asthma and cystic fibrosis. Recently, we have begun to explore the physical properties of airway mucus - thickness, stickiness, and adhesiveness - using an instrument called a rheometer. The rheology of airway mucus has not been investigated in detail, but the research resources of the CVRI are well suited to making progress in this area. For example, in our clinical laboratories in the CVRI, we can collect induced sputum from volunteers in a carefully controlled way, and in our bench laboratories we can make careful rheological measures. These rheologic measures are allowing personnel in our lab to explore new strategies for breaking up the mucus that normally clogs airways.

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.

David G Gardner, M.D.
Professor in Residence

Research Interests:
Cardiovascular endocrinology, natriuretic peptides, natriuretic peptide receptors, vitamin D, nuclear hormone receptors, growth and hypertrophy in cardiovascular system and kidney, obesity-related cardiomyopathy.

Summary:
Our laboratory is interested in understanding the role that hormones play in the control of growth and function in the cardiovascular system (heart and blood vessels). We are particularly interested in vitamin D and the natriuretic peptide hormones, two classes of hormones that have beneficial effects on cardiovascular function.

Zev Jordan Gartner, M.S. , Ph.D.
Acting Assistant Professor

Research Interests:

Summary:
We use RNA and DNA, a cell's molecular information carriers, as structural components to build and perturb living systems.

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.

Warren M Gold, B.A., M.D.
Professor

Research Interests:
Pulmonary physiology, exercise physiology, pulmonary vascular obstruction, early diagnosis, dyspnea, asthma, COPD, diffusing capacity.

Summary:

Michael D Grabe, Ph.D.
Associate Professor

Research Interests:
Membrane channels and transporters, molecular simulation, continuum electrostatics and elasticity theory

Summary:
Our lab uses computational methods to understand biological phenomena. We are primarily interested in the mechanical operation of ion channels and transporters, which move ions and small molecules across membranes. Additionally, we use theoretical approaches to explore how these membrane proteins work together to regulate ion homeostasis in organelles such as the lysosome and Golgi. Lastly, we are developing methodologies for predicting the stability of membrane proteins to understand how mutations give rise to a loss of function, improper trafficking or degradation.

Michael Gropper, M.D., Ph.D.
Professor In Residence

Research Interests:
Transfusion related acute lung injury, acute respiratory failure, acute respiratory distress syndrome, sepsis, ventilator associated pneumonia, resuscitation, mechanical ventilation, critical care outcomes

Summary:
My research interests are all focused on improving outcomes in critically ill patients in the ICU. These interests range from basic scientific questions regarding the mechanisms of harm from blood transfusions to asking about whether we efficiently utilize our precious resources, particularly at the end of life.

William Grossman, M.D.
Director, Center for Prevention of Heart & Vascular Disease

Research Interests:
Diastolic function of the left ventricle; Prevention of atherosclerosis, myocardial infarction, and stroke.

Summary:
Dr. William Grossman has been a pioneer in research on diastolic function of the left ventricle and is editor of the widely respected textbook, "Grossman's Cardiac Catheterization, Angiography and Intervention,: which is used by cardiology trainees around the world. Grossman is the Charles and Helen Schwab Endowed Chair in Preventive Cardiology, and Director, Center for Prevention of Heart & Vascular Disease Professor of Medicine, University of California, San Francisco

Daniel O Hart, PhD
Assistant Professor

Research Interests:
Zebrafish; development; transcription; stem cells

Summary:
The development of a multi-cellular organism from a single cell is a complex process that is regulated at many stages. One important level of regulation is the control of gene expression, that is, how and when genes are switched on or off to produce RNA and proteins. This process, transcriptional regulation, is critical for proper development. Disturbing this important step can have consequences for development and is often a hallmark of disease. It is therefore very important to understand the mechanisms underlying the transcriptional control of gene expression, and this is the broad aim of my lab.

We are particularly interested in understanding how general transcription factors can be used in specific ways to control genes. How they recognize where to bind in the genome, and what other factors (e.g. interacting proteins) may affect how they function to control development and differentiation.

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.

Samuel Hawgood, M.B., B.S., M.D.
Chancellor

Research Interests:
Structure and function of surfactant apoproteins

Summary:
Our research activity is focused on the biology of the pulmonary alveolus with a particular emphasis on the structure and function of the pulmonary surfactant apoproteins. The human lung is made up of some 500 million alveoli each with a diameter of 200 microns and a septal wall thickness of only 5-8 microns. The large surface area provided by this foam-like architecture is ideal for rapid respiratory gas exchange but necessitates some unique biological answers to the threat to structural stability posed by the problem of high surface tension and the constant exposure to environmental pollutants, allergens and microbes. Pulmonary surfactant, a lipoprotein secretion of the alveolar epithelial type II cell, stabilizes alveolar structure at low transpulmonary pressures by reducing the retractile surface forces that would otherwise act to collapse the lung at end expiration. The surfactant apoproteins also act as components of the pulmonary innate defense system protecting the lung from inflammation and infection.

A derangement of alveolar stability, secondary to a developmental deficiency of surfactant, is the major factor in the pathogenesis of the respiratory distress syndrome of the newborn (RDS). My interest in the biology of surfactant grew from clinical experience in neonatology where RDS is a major cause of neonatal death. I moved to UCSF in 1982 as a research fellow with Dr. John Clements, the scientist who discovered surfactant in the late 1950's. He started his own laboratory, focused on the proteins associated with surfactant, in 1984. By 1985 our laboratory had identified three novel surfactant-associated proteins, now known as SP-A, SP-B and SP-C, and had derived their primary structures from full-length cDNA and genomic clones. In 1993, Erica Crouch in St. Louis described a fourth protein, SP-D. The higher-order structure, genetic regulation, metabolism, and function of these proteins have been the focus of our research since that time.

We now know that the surfactant proteins have important roles in the activity of surfactant, particularly the ability to rapidly spread phospholipids at the alveolar surface. The proteins also regulate surfactant turnover and metabolism in the alveolus and play a part in non-antibody mediated response to infection and inflammation in the alveolus. The biology of these proteins is complex and they apparently function as interacting hetero-oligomers to mediate their multiple effects on surfactant biology. At least two of the surfactant proteins, SP-B and SP-C, are present in exogenous surfactants approved for clinical use and fatal human disease has been linked to inherited mutations in both these proteins. This clear link to human disease provides a strong rationale to obtain a detailed understanding of their structure and function.

Julien I Hoffman, M.D., F.R.C.P.
Professor Emeritus

Research Interests:
Pathophysiology of myocardial ischemia

Summary:
My research investigates the way in which the complex muscular architecture of the human heart functions, and what role different components play in heart failure. Current hypotheses of ventricular architecture emphasize the interaction of spiral and circumferential muscle layers, but one major hypothesis that there is a single folded muscular band is much in dispute. We know that the adult pattern is already complete at 14 weeks gestation, but there is no information about how the primitive cardiac tube becomes this complex multilayered structure. My colleagues and I have shown that different components of this muscle band may be affected in diastolic heart failure, and are seeking further information about how components of the band arise and how each component may be affected by disease.

I have ongoing research into the epidemiology of congenital heart disease but no specific problems are being studied at the moment.

Most of my previous research involved the control of the regional coronary circulation, with particular reference to the mechanisms of subendocardial ischemia. Although I am not actively working in this field now, I am collaborating with some bioengineers who are studying these problems.

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.

Holly A Ingraham, Ph.D.
Professor

Research Interests:

Summary:
Our research is focused on development of endocrine and brain regions that contribute to energy balance and reproduction. We concentrate on NR5A nuclear hormone receptors that specify cell fate in developing endocrine organs and the hypothalamus using structural biology, biochemistry and physiology.

Roshanak Irannejad, Ph.D.
Assistant Professor in Residence

Research Interests:
Internal membrane compartments as hubs of signaling

Summary:
To function properly, cells and tissue must receive and interpret a large variety of signals. They do so, in part, through signaling receptors, some of which reside on cell surfaces known as plasma membranes. We study adrenergic receptors, which are targets of commonly used medicines including alpha and beta blockers. By developing a new class of sensors that allow for detection and visualization of signaling events in living cells, we made the unexpected finding that signaling cues to cells not only act on cell surface receptors but also on internal cellular compartments. This observation raises numerous questions pertaining to fundamental aspects of cell signaling and suggests that cells have spatially compartmentalized signaling hubs. This basic biological insight has clinical implications as well. For example, certain beta-blockers are known to have differential clinical efficacies but the underlying reasons for these differences are not known. We have found that different beta blockers act on distinct hubs of signaling. Beyond their well-established roles in cardiac physiology, adrenergic receptors regulate a wide variety of important physiologically and behavioral processes. We are using our newly developed tools to investigate the consequences of signaling from internal compartments on a range of cellular, physiological, and behavioral outcomes.

Lily Y Jan, B.Sc., M.Sc., Ph.D.
Professor

Research Interests:
Studies of potassium channels

Summary:
Ion channels such as potassium channels and calcium-activated chloride channels are important for the function of the heart, lung, and vasculature. Starting with molecular characterizations of the channel proteins, we try to understand how these channels work and how their activities are regulated under various physiological conditions

David J Julius, S.B., Ph.D.
Chair and Professor

Research Interests:

Summary:

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

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.
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.

Joel S Karliner, A.B., M.D.
Prof of Medicine Emeritus

Research Interests:
Cardioprotection

Summary:
Our lab is devoted to studying cardioprotection. We employ isolated cells and hearts subjected to oxygen deprivation that simulate a heart attack. We then use promising drugs that salvage heart muscle during and after a heart attack, confirm that they are efficacious, and then study their mechanism of action.

Thomas B Kornberg, B.A., Ph.D.
Professor

Research Interests:
Developmental regulation

Summary:
My laboratory investigates the mechanisms that pattern developing organs. We carry out our studies on the fruit fly, as it offers many advantages with its ready accessibility to histological analysis and the ease with which genetic manipulations can be made. We focus on two systems – the fly wing and the fly lung. Both are model systems that offer opportunities to identify and characterize basic genetic and molecular mechanisms that are relevant to human development and disease.

Laura L Koth, M.D.
Associate Professor

Research Interests:
Sarcoidosis Granulomatous Lung Diseases T cells Monocytes chemokines

Summary:
Dr. Koth's research program is structured around the study of samples from human research studies. With the breath of research techniques that can be applied to human samples to learn about disease, Dr. Koth is taking a direct approach in the study of lung diseases. Dr. Koth's current focus involves understanding the inflammatory disease called sarcoidosis. This is not a disease as common as asthma, but it affects both young and middle aged people and causes significant morbidity and mortality. More awareness and funds are needed if we hope to understand the complicated biology of the disease. For example, many of the main immune subsets of the body are abnormally regulated in this disease. Most research has focused on the traditional T-cell. For example, it is thought that specific T cells are very activated and making inflammatory products which are contributing to and continuing the disease. However there are other immune cells that have not been studied adequately. Dr. Koth's lab has taken an active interest in these other types of immune cells. One reason for this is that we have identified, using Genomics research, that specific transcripts in the blood actually predict whether a specific patient will have progressive disease or not. She and her lab are now pursuing a line of investigation to understand where this 'biomarker message' is coming from in order to be able to stop it.

Dr. Koth's lab is also interested in using state-of-the-art technology to think about new therapies for this disease. We are looking into cutting-edge translational methods of expanding a type of immune cell responsible for down regulating the inflammatory process of the body. To perform these experiments in clinical trials will require significant financial support and we are seeking this input in order to move this very exciting potential treatment forward. The other aspect of my research program includes the development of a 'center of excellence in sarcoidosis'. This program will be designed to include both excellence in clinical care and novel clinical studies. Developing clinical care standards is an important area in managing sarcoidosis patients since sarcoidosis is a chronic disease that may be active for 10-20 years or more. Thus, a full-service clinical care program would facilitate the creation of clinical management tools and treatment regimens (developed as products from clinical trials networks) to address three arms of care in sarcoidosis: 1) organ damage, 2) symptom control, and 3) psychosocial aspects of living with the disease.

Ronald M Krauss, M.D.
Adjunct Professor

Research Interests:

Summary:
Lipoprotein metabolism and risk of cardiovascular disease

Despite recent advances in treatment, cardiovascular disease (CVD) remains the leading cause of death in the US and will soon achieve this status globally. Our group's research is aimed at addressing three major challenges for reducing this enormous disease burden. First, standard diagnostic procedures do not identify a high proportion of children and adults who are at risk for CVD. We have developed and implemented a sophisticated new procedure that, by analyzing individual lipoprotein particles, provides more specific information than that afforded by ordinary cholesterol testing, and hence is capable of improving both the assessment and management of CVD risk. Second, dietary and lifestyle guidance has failed to substantially impact CVD risk factors, particularly those related to overweight and obesity. We have demonstrated that carbohydrate restriction can reverse the high risk lipid profile found in a high proportion of overweight and obese individuals even without weight loss, and that this effect is independent of saturated fat intake. These findings have helped support dietary guidelines that place a greater emphasis on limiting refined carbohydrates than fats. Third, despite the awareness of wide interindividual variability in response to treatments aimed at reducing CVD risk, the potential benefits of applying genomic tools for developing personalized approaches for maximizing CVD risk reduction have not been realized. A major component of our research program has been the application and development of genomic methodology for dissecting genetic influences on the therapeutic responses to statins, the most widely prescribed class of drugs for reducing CVD risk.

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

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.

Stephen C Lazarus, M.D.
Professor of Clinical Medicine

Research Interests:
Role of inflammation in asthma and COPD, mucus hypersecretion.

Summary:
Asthma affects 5-10% of the US population, and deaths from asthma have increased for several decades. COPD is the 4th leading cause of death in the US. Understanding the mechanisms involved in these diseases and how best to treat them will contribute to better outcomes.

Randall J Lee, M.D., Ph.D.
Prof of Clin Med

Research Interests:
Arrhythmias, radiofrequency catheter ablation, implantable cardioverter/defibrillators, genetics, gene therapy, tissue engineering, stem cells, cell transplantation, biopolymers, antibodies, myocardial reconstruction/regeneration

Summary:
The research program integrates the disciplines of cell biology, bioengineering and cardiology. A tissue engineering approach is being used to investigate the potential application of cardiovascular reconstruction/regeneration. The use of stem cells and engineered polymer scaffolds are being investigated in heart attach models to determine their usefulness and safety in repairing damaged heart tissue.

Wendell A Lim, Ph.D.
Professor

Research Interests:
Signal transduction, synthetic biology, systems biology, structural biology, protein-protein interactions, cell motility, MAP kinase cascades, GTPase pathways

Summary:
Wendell Lim's Lab is working on creating a detailed instruction manual - a sort of user's guide - that explains how biochemical circuits control a cell's function and ultimately its fate. The long-term goal is to use the instruction manual to help scientists design cells to deliver therapeutic payloads, repair cancerous lesions, or attack microscopic pathogens. Cells are complex mechanical and sensing devices that can carry out highly complex tasks, such as secreting antibodies or forming repair structures like blood clots and bone. Cells contain signaling pathways that take in and integrate vast amounts of information about the cells' environment, and they process and use this information to make complex decisions about how to respond to changing environmental conditions. If more is understood about how these processes work, there is the potential to change cells and help solve problems in biotechnology or health, and to treat disease more rationally.

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.

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.

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.

Daniel L Minor, Ph.D.
Professor

Research Interests:
Membrane proteins; potassium channels, calcium channels

Summary:
Hearts, brains, muscles, and senses require electrical signals to function. We aim to understand the basic cellular components responsible for generating electrical activity. We focus on understanding the structure, function, and regulation of ion channels from a high-resolution viewpoint, understanding how channel mutations cause disease, and on developing new tools for controlling channel function.

Keith E Mostov, M.D., Ph.D.
Professor

Research Interests:
Polarized epithelial membrane traffic and epithelial morphogenesis.

Summary:
How do individual cells organize to form a multicellular tissue? An individual cell can exhibit many different behaviors - proliferation, migration, adhesion, polarization, differentiation, and death. But to build a tissue, a population of cells must coordinate these individual behaviors across space and time. Little is understood about the mechanisms that orchestrate the actions of single cells during morphogenesis. To analyze these issues, we are studying how epithelial cells form three-dimensional organs. Epithelia are coherent sheets of cells that form a barrier between the interior of the body and the outside world. Internal epithelial organs contain two types of building blocks, cysts and tubules. Our experimental strategy uses culture of epithelial cells in a three-dimensional extracellular matrix. Single cells plated in matrix grow to form hollow cysts lined by a monolayer of cells. We have discovered a pathway containing the small GTPase, rac1, alpha1-beta3 integrin, and laminin, which coordinates cell polarity, so that apical surfaces of the cells are all oriented towards the cyst lumen. Cysts are remodeled into by growth factors, which cause transient dedifferentiation and migration, followed by redifferentiation into polarized epithelial cells lining the tubule.

Spatial asymmetry is fundamental to the structure and function of most eukaryotic cells. A basic aspect of this polarity is that the cell's plasma membrane is divided into discrete domains. The best studied and simplest example of this occurs in epithelial cells, which line exposed body surfaces. Epithelial cells have an apical surface facing the outside world and a basolateral surface contacting adjacent cells and the underlying connective tissue. These surfaces have completely different compositions. Epithelial cells use two pathways to send proteins to the cell surface. Newly made proteins can travel directly from the trans-Golgi network (TGN) to either the apical or basolateral surface. Alternatively, proteins can be sent to the basolateral surface and then endocytosed and transcytosed to the apical surface. We are studying the machinery that is responsible for the specificity and regulation of polarized membrane traffic in epithelial cells. I will discuss several recent results.

1. The SNARE hypothesis provides a unified model for how intracellular vesicular targeting and fusion work. Proteins on transport vesicles, known as v-SNAREs, pair with corresponding t-SNAREs on target membranes, leading to vesicle fusion. The correct pairing of particular v- and t-SNAREs can provide a mechanism for specificity of targeting and fusion. Polarized epithelial cells are an ideal system in which to test the role of SNAREs in specificity, as these cells contain two plasma membrane targets, the apical and basolateral surfaces, as well as multiple classes of vesicles traveling to each surface. We have found that that the t-SNARE syntaxin 3, is involved with transport to the apical surface, while the related t-SNARE, syntaxin 4, is utilized for transport to the basolateral surface.

2. The polymeric immunoglobulin receptor (pIgR) transcytoses IgA from the basolateral to the apical surface. Transcytosis is stimulated by ligand binding. Binding of IgA causes dimerization of the pIgR, which leads to activation of a non-receptor tyrosine kinase, p62Yes. Mice knocked out for this kinase are deficient in IgA transport. Phosphatidylinositol-specific phospholipase C gamma is activated, resulting in production of DAG and IP3. The DAG activates protein kinase Ce, which stimulates transcytosis. The IP3 raises intracellular free calcium, which also stimulates transcytosis. Stimulation of transcytosis also involves the small GTPase, rab3b, which directly interacts with the pIgR.

3. When epithelial cells, such as MDCK cells, are plated in a 3 dimensional collagen matrix, the cells form hollow, polarized cysts with the apical surface facing the lumen of the cyst. Overexpression of a dominant negative form of the small GTPase, rac, retards lumen formation and leads to a partial reversal of polarity, with the apical surface oriented towards the outside of the cyst. Growth of the cysts laminin rescues this phenotype, indicating that interfering with rac function interferes with the ability of the cell to assemble, laminin, which normally provides a spatial cue.

4. When collagen-grown cysts are stimulated with hepatocyte growth factor (HGF), the cysts develop branching tubules, providing a simple model system for studying tubulogenesis. The exocyst is an eight-subunit complex involved in targeting transport vesicles to specific regions of the plasma membrane. We have found that HGF treatment causes the exocyst to relocalize from the region of the tight junction to the growing tubule, indicating that new membrane is being directed to the tubule. Overexpression a subunit of the exocyst, hSec10, causes the cysts to elaborate an increased umber of tubules, indicating a direct connection between membrane traffic and tubulogenesis.

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.

Jeffrey E Olgin, M.D.
Professor and Chief

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:

David Pearce, B.A., M.D.
Professor of Medicine

Research Interests:
Epithelial biology as it relates to cardiovasculare function: hypertension, fluid and electrolyte regulation.

Summary:

Tien Peng, M.D.
Assistant Professor

Research Interests:
Developmental pathways in the maintenance of adult tissue homeostasis

Summary:
Our laboratory is interested in studying how key developmental pathways continue to persist in adulthood to maintain normal homeostatic organ function. We are particularly focused on the mesenchymal cell types (e.g. fibroblasts, pericytes, and etc.) that are poorly understood and lack precise anatomical definition, but are integral to the structural integrity and function of adult organs such as the lung.

David R Raleigh, M.D., Ph.D.
Assistant Professor In Res

Research Interests:
Hedgehog signaling, developmental biology, brain tumors and molecular therapeutics

Summary:
More children die from brain tumors than any other type of cancer, and the most common type of brain tumor in children is medulloblastoma. Like all cancers, medulloblastoma is caused by uncontrolled cell growth. Approximately one-third of medulloblastoma cancers arise when a particular signal that tells brain cells to grow, called Hedgehog, gets stuck in the 'on' position. We are interested in uncovering exactly how Hedgehog signals tell cancer cells to grow. To do so, we are investigating how the Hedgehog pathway is activated, and how Hedgehog activation regulates the expression of other signals to influence cell growth. Understanding how Hedgehog signals cause cancer may show us how to turn off these signals, and potentially, lead to new therapies for medulloblastoma.

Rita F Redberg, M.D., M.Sc.
Professor

Research Interests:

Summary:
Dr. Rita F. Redberg's research interests are non-invasive imaging of the coronary arteries comparing transesophageal echo with ultrafast CT and magnetic resonance imaging. Her ongoing research studies include a stray of the role of exercise in heart disease in women. She also does research in exercise echo evaluation of valvular and congenital heart disease as well as the use of transesophageal echo imaging in cardiopulmonary resuscitation.

Jeremy F Reiter, M.D., Ph.D.
Associate Professor

Research Interests:
Signaling, primary cilium, stem cell, Hedgehog, Wnt

Summary:
In the process of development, a single egg cell develops into a complex organism. Understanding how that first cell generates such astonishing complexity is one of biology's great tasks. Not only is this task fundamental to our understanding of ourselves, but it is also critical to understanding the causes of birth defects and other diseases. Many of the mechanisms underlying development depend on intercellular communication, the ability of cells to send and receive information. Secreted signaling proteins can communicate many different types of information, from what type of cell a cell should become to whether a cell should live or die. We are studying the mechanisms by which a cellular organelle, the primary cilium, receives and interprets these signals during development. We are also studying how mistakes in these signals contribute to diseases such as cancer.

Jason R. Rock, PhD
Assistant Professor

Research Interests:
Stem cells in lung development, maintenance, and disease

Summary:
We investigate how the many epithelial and stromal cell types of our lungs are generated during development, maintained for a lifetime and regenerated following injury. To do this, we use in vivo and in vitro models to identify and test the progenitor capacity of putative stem cell populations. We posit that aberrant stem cell behaviors explain many features of common lung diseases such as mucous cell hyperplasia and pulmonary fibrosis. For this reason, we study the molecular mechanisms and environmental influences (i.e., niche) that regulate the division and differentiation of stem cells along various lineages. Our ultimate goal is to identify genetic, molecular and cellular therapies for the treatment of lung disease.

David H Rowitch, M.D., Ph.D.
Professor

Research Interests:
Developmental biology, neural tube, CNS cell cycle control and tumorigenesis, cell fate specification, gliogenesis, oligodendrocyte differentiation and myelination, Sonic Hedgehog signaling, transcription factors, Olig bHLH proteins, multiple sclerosis, cerebral palsy, brain cancer.

Summary:
Dr. Rowitch's laboratory investigates common mechanisms in brain development and neurological diseases such as Multiple Sclerosis and brain cancer. Upon moving to UCSF in 2006, Dr. Rowitch has focused on developing a new translational research program focused on Cerebral Palsy, the leading cause of intellectual disability in the United States.

Melvin M Scheinman, M.D.
Professor

Research Interests:
Mechanisms of cardiac arrhythmias. Cardiac electrophysiology. Catheter ablation of arrhythmogenic foci.

Summary:
My current research interests involve looking at mechanisms of supraventricular arrhythmias with respect to ablative therapy. In addition, we have initiated a cardiac genetic arrhythmic clinic – to help define newer genes in causation of serious ventricular arrhythmias.

We are also studying the mechanism of atypical atrial flutter in humans. We have described the occurrence of double-wave reentry (1), and have extended these observations to describe an entity known as lower-loop reentry (2) which is also isthmus dependent. We have described a new type of atypical atrial flutter involving the left membranous septum and this work was presented at the North American Society of Pacing and Electrophysiology meetings (3).

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.

Ian Bass Seiple, Ph.D.
Assistant Prof in Residence

Research Interests:
Synthesis of biologically active small molecules

Summary:
Despite centuries of innovation, chemistry is often still the limiting factor in the development of small molecule drug candidates, molecular probes, or novel chemical libraries. Many molecules that have tremendous biological potential are challenging to modify with known chemical methodologies. The overarching goal of our program is to develop practical methods for the synthesis of molecules that have previously been inaccessible. Many of our current projects are focused on the synthesis of novel antibiotics that can be used to treat life-threatening infections of the heart, lungs, and upper respiratory tract. 

Dean Sheppard, M.D.
Professor and Chief

Research Interests:
In vivo function of integrins and molecular basis of lung diseases

Summary:
Dean Sheppard's laboratory studies how cells respond to and modify their surroundings using receptors called integrins. They have found important roles for integrins in lung and kidney fibrosis, septic shock, acute lung injury, asthma and stroke and are testing drugs targeting integrins in animal models and in people affected by these diseases.

Kevan M Shokat, Ph.D.
Professor and Chair

Research Interests:
DESIGN OF DRUGS TO TREAT CARDIOVASCULAR DISEASE, CANCER, AND AUTOIMMUNE DISEASES.

Summary:

Xiaokun Shu,
Assistant Professor

Research Interests:
Protein Rational Design and Directed Evolution for Biology and Medicine

Summary:
We are developing technologies to bridge the gap between clinical medicine and molecular biology. Their successful use in biomedicine will significantly improve treatment of disease.

Anthony K Shum, M.D.
Asst Professor in Residence

Research Interests:
Autoimmune lung disease, interstitial lung disease, ER stress, lung injury, lung fibrosis, lung autoantigens

Summary:
The Shum lab is interested in understanding the immune mechanisms that lead to lung inflammation and fibrosis in patients with autoimmune disorders. Through human and mouse studies, we seek to define the critical factors that lead to autoimmune lung disease in order to speed the development of diagnostic tests and treatments for patients.

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.

Deepak Srivastava, M.D.
Director and Professor

Research Interests:
Developmental biology, pediatric cardiology, congenital heart defects, organogenesis, human genetics, stem cells, cardiac repair

Summary:
Dr. Srivastava's work focuses on understanding cardiac development by elucidating the molecular events regulating early and late developmental decisions that instruct progenitor cells to adopt a cardiac cell fate and subsequently fashion a functioning heart. This foundation has been used to discover the genetic basis for some congenital heart malformations.

David F Teitel, M.D.
Prof In Res

Research Interests:
Pediatric cardiology, developmental cardiovascular physiology, cardiac mechanics, pediatric interventional cardiac catheterization, computer technology in cardiology, heart center administration, medical education, digital technology in learning, bioinformatics.

Summary:
Congenital heart disease is extremely common, occurring in about 1% of all births. My goals are to advance our knowledge of heart function in such infants and children, and to develop new methods to treat them, using medicines and catheter based techniques rather than surgery.

Vasanth Vedantham, M.D., Ph.D.
Assistant Clinical Professor

Research Interests:
Development and function of the cardiac conduction system; molecular regulation of cardiac pacemaker cells; mechanisms of cardiac arrhythmias

Summary:
Our lab is focused on cardiac pacemaker cells, specialized cardiomyocytes whose autonomous electrical activity allows the sinoatrial node to serve as the heart's natural pacemaker. Specific questions include: How are pacemaker cells different from regular heart cells at the level of gene expression and regulation? How does their unique gene expression signature confer their distinctive electrophysiological properties? How have selection pressures generated functional differences in pacemaker cells among different vertebrate species? What are the molecular mechanisms that guide pacemaker cells to integrate electrically with the rest of the heart to form a node? How do pacemaker cell biology and function change in response to physiological and pathological stress? What is the mechanistic link between sinus node dysfunction and atrial fibrillation? Our approaches include mouse genetics, whole-animal and ex-vivo electrophysiology, cellular and molecular electrophysiology, gene expression analysis, and bioinformatics. Ultimately, we hope to design novel treatments for patients suffering from heart rhythm disorders, including sinus node dysfunction and atrial fibrillation

Mark E Von Zastrow, Ph.D., M.D.
Professor

Research Interests:
Subcellular organization and dynamics of receptor-mediated signaling systems in eukaryotic cells.

Summary:
Our laboratory studies mechanisms by which receptors that control cardiovascular biology are regulated. These receptors are important therapeutic targets and their regulation is known to be disturbed in a number of important disease states.

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.

Biao Wang, Ph.D.
Assistant Professor

Research Interests:
Obesity, diabetes, hormones, cAMP, kinase, signaling transduction, transcriptional regulation

Summary:
Type II diabetes mellitus accounts for 90-95% of all cases of diabetes, and this heterogeneous disorder afflicts an estimated 6% of the adult population in Western society. Energy imbalance by high calorie intake and/or lack of physical activity can lead to obesity, which is often associated with an increased risk of developing insulin resistance followed by type II diabetes. Our research is focused on understanding how circulating hormones modulate energy balance in multiple metabolic tissues, and how disruption of these hormonal actions contributes to pathophysiology of type II diabetes.

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.

Prescott G Woodruff, M.D., M.P.H.
Associate Professor

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.

Allison Wanting Xu, M.Sc., Ph.D.
Associate Professor

Research Interests:
Hypothalamic regulation of energy balance, obesity and type 2 diabetes

Summary:
Our lab's major research focus is to understand the mechanisms by which energy balance is regulated. We use a combination of mouse genetics, whole body physiology and real time imaging approaches to elucidate the function of specific hypothalamic neurons and how they integrate peripheral metabolic signals under distinct physiologic conditions.

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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