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CVRI Scientists
Muscle biology and heart failure
Harold S. Bernstein, M.D., Ph.D.
Professor in Residence, Pediatrics
Research Interests:
Stem cells, cardiac muscle, skeletal muscle, cell cycle regulation
Summary:
Each year, more than 900,000 people in the U.S. experience a heart attack, and about 500,000 die from complications of heart failure. Heart failure occurs when heart muscle cells are damaged and the heart is unable to meet the demands placed on it by the body. Unlike other organs, the heart is unable to repair itself. We seek to develop new ways of stimulating heart muscle repair or producing replacement heart muscle cells to be used for repair, thereby treating or avoiding heart failure.
Specifically, our laboratory studies the mechanisms regulating cell division, and how such processes play a role in cardiovascular biology and disease. To this end our work has focused on three main areas of basic investigation: 1) mechanisms of cell cycle withdrawal during muscle differentiation; 2) cardiac fate determination in myogenic stem cells, and; 3) the role of cell cycle machinery in cellular hypertrophy. In addition, we recently have initiated two new areas of translational and clinical research that apply their understanding of how muscle cells behave to the development of new diagnostic and therapeutic approaches to heart failure: 4) human embryonic stem cell-based therapies for heart failure; and 5) identification of biomarkers of heart failure in patients with congenital heart disease.
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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.
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Frances M Brodsky, B.A., D. Phil.
Professor
Research Interests:
REGULATION AND FUNCTION OF CLATHRIN-MEDIATED MEMBRANE TRAFFIC
Summary:
Critical pathways of human nutrition are controlled by clathrin proteins that are present inside cells. Clathrins control uptake of cholesterol from the bloodstream and uptake of glucose into skeletal muscle, processes that influence heart disease and diabetes. The laboratory focuses on understanding molecular aspects of clathrin function for insight into cardiovascular disease.
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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.
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Kanu Chatterjee, M.D.
Professor
Research Interests:
Diagnosing and managing coronary artery disease, heart failure and pulmonary hypertension.
Summary:
Cardiologist Dr. Kanu Chatterjee has more than 30 years of experience in diagnosing and managing coronary artery disease, heart failure and pulmonary hypertension. He is a world-renowned researcher in vascular reactivity and heart failure and has pioneered the study of drugs, such as ACE inhibitors and vasodilators, that have become the standard of care for heart failure.
He serves on advisory boards for pulmonary hypertension study designs and on data, safety and monitoring committees for multi-center trials of pulmonary hypertension treatments. Certified in internal medicine and cardiovascular disease, he is on the editorial boards of professional journals in cardiology. He was director of the Inpatient Cardiology Service at Cedars-Sinai Medical Center in Los Angeles before joining the UCSF Medical Center staff in 1975 as director of the Cardiac Care Unit and associate chief of Cardiology. He is the Ernest Gallo Distinguished Professor of Medicine at the University of California at San Francisco. A research center at UCSF, called the Chatterjee Center for Cardiac Research, was named after him.
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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 proteinÐcoupled receptors. We combine genetic engineering, stem cells and new computer programs to find new treatments of cardiovascular disease.
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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.
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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.
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William Grossman, M.D.
Division Chief
Research Interests:
Diastolic function of the left ventricle
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 Meyer Friedman Distinguished Professor of Medicine at UCSF and chief of the Cardiology Division at UCSF Medical Center.
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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.
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David J Julius, S.B., Ph.D.
Chair and Professor
Research Interests:
Summary:
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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.
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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.
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Michael J Mann, M.D.
Research Interests:
1. Molecular/cellular biology and molecular genetics of atherosclerosis and heart failure.
2. Development of hybrid surgical and molecular/cellular therapies for heart disease.
3. Stem and progenitor cell transplantation for cardiovascular regeneration.
4. Cardiovascular tissue engineering.
5. Reduction to clinical practice of current methods in genetic, molecular and cellular disease intervention.
6. Novel targeted molecular therapies for lung cancer.
7. Molecular profiling of cancers for personalized medicine.
8. Development of novel methods of in vivo/ex vivo gene therapy and gene transfer.
9. Novel approaches to therapeutic neovascularization for coronary and peripheral ischemic disease.
10. Cardiovascular cell cycle biology.
11. Myocardial gene therapy.
Summary:
Dr. Mann's research focuses on the molecular and cellular biology of heart disease with an emphasis on practical ways to develop new treatments for heart failure. These involve potential gene and molecular therapies, combinations of molecular and cell-based treatments with surgical reconstruction, and evaluation of novel materials for the development of bioartificial replacements of lost or damaged heart tissue.
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Robin M. Shaw, M.D., Ph.D.
Asst Professor In Residence
Research Interests:
Cardiac Electrophysiology, Ion Channels, Arrhythmia, Sudden Cardiac Death, Heart Failure
Summary:
The basic function of the heart is to work as a pump, circulating blood through the lungs and the rest of the body. Each heartbeat, millions of individual heart cells contract in synchrony for one overall large contraction. Improper contraction results in congestive heart failure and improper synchrony results in sudden cardiac death. My laboratory studies the basic biology of heart cell contraction and synchronous communication with a goal of developing novel treatment strategies of both heart failure and sudden cardiac death.
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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.
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Matthew L Springer, Ph.D.
Associate 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. The laboratory is studying differential responses of cardiac and skeletal muscle to angiogenic gene therapy in mice, focusing on effects of VEGF and pleiotrophin on the vasculature. Further interests center in the therapeutic effects of bone marrow cell implantation into the heart after myocardial infarction, using an ultrasound-guided injection approach that we have developed in collaboration with the Yeghiazarians lab, with a special emphasis on the therapeutic implications of the age and cardiac disease status of the cell donor. Similarly, the lab is studying the effects of age and disease on circulating 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 cigarette smoke exposure and dietary flavanols.
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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.
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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.
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