Category: Site Parnassus


Sagar P. Bapat, MD, PhD

Research Interests:
Development of a novel T cell therapy to induce beige adipogenesis

Summary:
Type 2 diabetes is a leading cause of mortality in the United States, and its prevalence continues to rise in concert with the rising prevalence of obesity, the predominant risk factor for developing insulin resistance and diabetes. Obesity can result from a multitude of different complex physiological and socioeconomic conditions that individuals are often unable to overcome. Simply stated however, obesity is a manifestation of excessive storage of energy. Consequently, it could potentially be mitigated by turning on the body’s dormant systems for burning, not storing, that energy. In this proposal, we will develop regulatory T (Treg) cells as a powerful class of engineered, non-destructive cellular immunotherapies to tackle obesity and its co-associated metabolic disease type 2 diabetes. We will engineer fat-localizing Treg cells to deliver signals to convert energy-storing adipose tissue (AT) into energy-burning AT, thereby reversing or preventing obesity and insulin resistance in mice (and eventually humans.)

https://diabetes.ucsf.edu/lab/bapat-lab

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Jeffrey O. Bush, Ph.D.

Research Interests:

Signaling control of mammalian morphogenesis and congenital disease

Summary:

Our lab studies basic mechanisms by which signaling between cells coordinates mammalian morphogenesis. Understanding this control has significance beyond its fundamental importance in development since birth defects are the leading cause of death for infants during the first year of life. We utilize multiple approaches based in mouse genetics to understand fundamental signaling processes as they relate to development and disease with particular foci in the craniofacial and respiratory systems. In addition to mouse genetics approaches, we utilize human ES/IPSCs, biophysical approaches, multiomics, and live imaging to understand the cellular and molecular control of morphogenesis.

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Matthew L Kutys, Ph.D.

Research Interests:

Notch receptor signaling and chemo-mechanical regulation of vascular barrier, molecular regulation of endothelial cell morphodynamics during angiogenic sprouting and in cerebral small vessel disease, cardiac myocyte sarcomerogenesis, and angiocrine niche contribution to parenchymal tissue development, cancer, and infectious disease progression. 

Summary:

Research in the Kutys Lab is focused on achieving a molecular and physical understanding of biological mechanisms that interact across time and length scales to enable emergent, tissue morphogenic behaviors. Central to our efforts is the development and application of biomimetic microphysiological culture models,  organ-on-chip systems, that incorporate three-dimensional (3D) organotypic architectures and permit the study of human tissue development, regeneration, and pathogenesis with unprecedented resolution and biological control. Combining these models with innovative molecular technologies and high content microscopy, a major focus of my laboratory is understanding orchestration of tissue morphogenic behavior and cell fate specification by cell-cell and cell-extracellular matrix (ECM) adhesion complexes during cardiovascular development and disease.

Current projects in the lab focus on: Notch receptor signaling and chemo-mechanical regulation of vascular barrier, molecular regulation of endothelial cell morphodynamics during angiogenic sprouting and in cerebral small vessel disease, cardiac myocyte sarcomerogenesis, and angiocrine niche contribution to parenchymal tissue development, cancer, and infectious disease progression. 

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Akinyemi Oni-Orisan, PhD

Research Interests:

Pharmacogenomics, Cardiovascular drugs, Health disparities

Summary:

Cardiovascular disease is the most common cause of morbidity and mortality in the United States, affecting almost 100 million adults and costing over $300 billion. Death from cardiovascular disease had been steadily declining since the 1970s due in part to remarkable advances in pharmacotherapy, but more recently has started to worsen. Although the reasons for this reversing trend are likely multifactorial, it is evident that better optimization of therapy may help to improve this recent worsening. In particular, there exists considerable interindividual variability in response to cardiovascular drugs. We hypothesize that the discovery and clinical validity of molecular biomarkers for cardiovascular disease drug response will allow clinicians more precise select cardiovascular pharmacotherapy regimens, thereby improving population-wide cardiovascular health outcomes. The overall research goal of my group is to improve pharmacological regimens for the prevention and treatment of cardiovascular disease through precision medicine. To accomplish this objective, we combine computational approaches in pharmacogenomics, pharmacometrics, and pharmacoepidemiology using electronic health record-linked biobanks. In addition, only ~14% of participants from all genome wide association studies are of non-European descent, despite accounting for ~86% of the global population. This underrepresentation has the strong potential to exacerbate health disparities. Thus, another goal of our group is to ensure that study populations of genomics research studies are inclusive so that advances can benefit all. In accord with our overall research objectives and the approaches that we employ, we are currently investigating genetic determinants of efficacy and safety for hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor therapy in diverse populations.

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Mark Looney, M.D.

 

Research Interests:

Pulmonary and Critical Care Medicine, acute lung injury, acute respiratory distress syndrome, blood transfusions, transfusion-related acute lung injury, neutrophils, neutrophil extracellular traps, platelets, lung transplantation

Summary:

My laboratory is broadly interesting in study innate immune biology in the normal and injured lung.  Using pre-clinical models of acute lung injury, we have focused on neutrophils and platelets, the latter being a bon a fide immune cell with powerful inflammatory potential.  One consequence of platelet-neutrophil interactions is the formation of neutrophil extracellular traps (NETs), which we study in both sterile and pathogen-induced lung injury models.  We are determining the mechanisms by which platelets trigger NETs and novel pathways to target NETs—which we have discovered are overall barrier disruptive in the lung.   

We also use two-photon intravital lung microscopy as a tool for discovery.  Using this technique, we have determined that the lung is a major source of mature platelet production in mice.  Furthermore, megakaryocytes reside in the extravascular lung and may have potent local immune effects.  The lung also contains a wide-range of hematopoietic progenitors, which have the capacity to leave the lung and engraft in the bone marrow for multi-lineage blood production.  We are determining the niche-promoting factors responsible for hematopoietic progenitor residence in the lung and the contributions of these cells to the local immune repertoire.

We have an expanding interest in lung transplantation studies, including ischemia-reperfusion injury (primary graft dysfunction) and modeling chronic lung allograft dysfunction (bronchiolitis obliterans).  We use the mouse single lung transplantation technique for these studies and to create lung chimeras for investigation.

UCSF Profiles Page: http://profiles.ucsf.edu/mark.looney


Rong Wang, Ph.D.

Rong Wang photo copy

Research Interests:
Molecular Regulation of Mammalian Arterial Venous Specification

Summary:

Molecular Regulation of Arterial-Venous Programming in Development and Disease   

 

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.

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David F Teitel, M.D.

Teitel

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.

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Matthew L Springer, Ph.D.

 

Matt 2016

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 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, the lab is 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, they 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.

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Anthony K Shum, M.D.

Shum

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.

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Michael A Matthay, M.D.

Matthay

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.

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Wendell A Lim, Ph.D.

Lim

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.

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