Category: Site Other Mission Bay

Ronald M Krauss, M.D.

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.

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

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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Holly A Ingraham, Ph.D.

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.

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

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.

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Zev Jordan Gartner, M.S. , Ph.D.

Research Interests:

Chemical Biology, Tissue Engineering, Systems and Synthetic Biology, Cancer Biology

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

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Bruce R Conklin, M.D.

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.

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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V Courtney Broaddus, M.D.

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.

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Kaveh Ashrafi, Ph.D.

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.

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Sam Hawgood as UCSF’s 10th Chancellor

UC Regents Confirm Sam Hawgood as UCSF’s 10th Chancellor

Sam Hawgood, MBBS, was confirmed Thursday morning as UC San Francisco’s 10th chancellor in a unanimous vote by the UC Board of Regents.

Hawgood, 61, whom University of California President Janet Napolitano tapped for the position July 9 after an international search for a leader for the $4.2 billion health sciences campus, has served as interim chancellor since April 1, when he succeeded Susan Desmond-Hellmann, MD, MPH.