Category: Muscle Biology and Heart Failure


Natalia Z Jura, PhD

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

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

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David J Julius, S.B., Ph.D.

Julius

Research Interests:
Summary:

My group is interested in understanding how signals are received and transmitted by the nervous system. In one aspect of our research, we have exploited the power of natural products to elucidate molecular mechanisms of touch and pain sensation. For example, we have asked how capsaicin, the main pungent ingredient in “hot” chili peppers, elicits burning pain, and how menthol, the cooling agent in mint leaves, evokes an icy cool sensation. Using these agents as pharmacological probes, we have identified ion channels on sensory nerve fibers that are activated by heat or cold, providing molecular insight into the process of thermosensation. With the aid of genetic, electrophysiological, and behavioral methods, we are asking how these ion channels contribute to the detection of heat or cold, and how their activity is modulated in response to tumor growth, infection, or other forms of injury that produce inflammation and pain hypersensitivity.

In addition to our work on somatosensation and pain, we also study the structure and function of specific neurotransmitter receptors, such as those activated by serotonin or extracellular nucleotides, and use genetic methods to identify roles for these receptors in physiological and behavioral processes, such as feeding, anxiety, pain, thrombosis, and cell growth and motility.

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Guo Huang, Ph.D.

Huang

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

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

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

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Website


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

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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Akiko Hata, Ph.D.

Hata

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

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

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William Grossman, M.D.

Grossman

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.

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David G Gardner, M.D.

Gardner

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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Rik M Derynck, Ph.D.

Derynck

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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Bruce R Conklin, M.D.

Conklin

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.

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

Bruneau

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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Yerem Yeghiazarians, M.D.

Yeghiazarians

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.


Brian L. Black, Ph.D.

Research Interests:
Cardiac and skeletal muscle development, differentiation, and function

Summary:
Tissues and organs form during mammalian embryonic development through the integration of numerous signaling and transcriptional pathways. Our major goal is to define pathways controlling organ formation to understand normal development, the molecular basis for congenital defects, and potential mechanisms for organ regeneration and repair.

We use a combination of gene knockouts, transgenic reporter assays, biochemical, computational, and genomic approaches to investigate basic developmental mechanisms. We primarily use the mouse as a model system, but several current projects also use cultured cells or zebrafish as models to understand developmental gene regulation. Current work in the lab is focused primarily on cell autonomous mechanisms underlying gene regulation, tissue specification, organ formation and metabolic control during cardiovascular, craniofacial, and neural crest development.

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