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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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. 

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.

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.

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.

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.

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.

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.

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