Category: Advanced technologies

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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Di Lang, Ph.D, MS

Research Interests:

Cardiac arrhythmias, sinoatrial node, calcium signaling, heart failure, stem cells, optical mapping

Summary:

Atrial fibrillation is the most common type of treated heart arrhythmia and is associated with the significant increase in the risk of stroke, heart failure and other heart-related complications. My research aims to understand the membrane nanodomain mediated compartmentalized cellular and molecular functioning and regulation of proteins in the atrial physiology and pathology and developing therapeutic strategies targeting the cell cytoarchitectures using animal models, primary cardiomyocytes and human induced pluripotent stem cells (hiPSCs). Specifically, I explore the compartmentalized molecular mechanisms of heart rhythm disorders (cardiac arrhythmias) and heart failure from multiple levels: from protein expression, signaling pathway regulation, and sub-cellular localization, protein-protein interaction, to electrical impulse propagation and repolarization of an intact heart. I develop and utilize multiple quantitative cutting-edge high-resolution imaging techniques on tissue, cellular, and microdomain levels as well as develop image processing algorithms.

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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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Balyn W. Zaro, Ph.D.

Research Interests:

Hematopoiesis, innate immunity and proteomics/mass spectrometry

Summary:

Our lab takes a chemical biology and proteomics approach to optimizing drug selectivity and studying the immune system and blood formation. We aim to profile how different types of cells metabolize drugs in order to develop more-selective therapeutics and are interested in identifying targets critical for modulating the innate immune response during cancer and infection.

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Nevan J. Krogan, Ph.D.

Research Interests:
Systems biology, quantitative unbiased approaches, proteomics, genetic interactions, proteinprotein interactions, post-translational modifications, cancer, infectious diseases, cardiac development, psychiatric disorders.

Summary:

Our research focuses on fundamental biological mechanisms, because cures to many diseases have been revealed by unexpected discoveries in the basic sciences. We use and develop complementing technologies that allow the unbiased study of the cell. We create maps to study how proteins work together in cells, and how this changes during different diseases, including infectious diseases, cancer as well as neurological and psychiatric disorders. We strongly believe that impactful research is accomplished when diverse groups of scientists work together, and therefore we are working in close collaboration with national and international experts from different disciplines on all of our projects.

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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

Ian Bass Seiple, Ph.D.

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.

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Orion D Weiner, Ph.D.

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.

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Lei Wang, Ph.D.

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.

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Mark E Von Zastrow, Ph.D., M.D.

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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Matthew L Springer, Ph.D.

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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Paul C Simpson, M.D.

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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