Category: Research Area

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

Vasanth Vedantham, M.D.

Research Interests: Development and function of the cardiac conduction system; molecular regulation of cardiac pacemaker cells; mechanisms of cardiac arrhythmias

Our lab is focused on cardiac pacemaker cells, specialized cardiomyocytes whose autonomous electrical activity allows the sinoatrial node to serve as the heart’s natural pacemaker. Specific questions include: How are pacemaker cells different from regular heart cells at the level of gene expression and regulation? How does their unique gene expression signature confer their distinctive electrophysiological properties? How have selection pressures generated functional differences in pacemaker cells among different vertebrate species? What are the molecular mechanisms that guide pacemaker cells to integrate electrically with the rest of the heart to form a node? How do pacemaker cell biology and function change in response to physiological and pathological stress? What is the mechanistic link between sinus node dysfunction and atrial fibrillation? Our approaches include mouse genetics, whole-animal and ex-vivo electrophysiology, cellular and molecular electrophysiology, gene expression analysis, and bioinformatics. Ultimately, we hope to design novel treatments for patients suffering from heart rhythm disorders, including sinus node dysfunction and atrial fibrillation

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David R Raleigh, M.D.

Research Interests: Hedgehog signaling, developmental biology, brain tumors and molecular therapeutics

More children die from brain tumors than any other type of cancer, and the most common type of brain tumor in children is medulloblastoma. Like all cancers, medulloblastoma is caused by uncontrolled cell growth. Approximately one-third of medulloblastoma cancers arise when a particular signal that tells brain cells to grow, called Hedgehog, gets stuck in the “on” position. We are interested in uncovering exactly how Hedgehog signals tell cancer cells to grow. To do so, we are investigating how the Hedgehog pathway is activated, and how Hedgehog activation regulates the expression of other signals to influence cell growth. Understanding how Hedgehog signals cause cancer may show us how to turn off these signals, and potentially, lead to new therapies for medulloblastoma.

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Roshanak Irannejad, Ph.D.

Research Interests: Internal membrane compartments as hubs of signaling

To function properly, cells and tissue must receive and interpret a large variety of signals. They do so, in part, through signaling receptors, some of which reside on cell surfaces known as plasma membranes. We study adrenergic receptors, which are targets of commonly used medicines including alpha and beta blockers. By developing a new class of sensors that allow for detection and visualization of signaling events in living cells, we made the unexpected finding that signaling cues to cells not only act on cell surface receptors but also on internal cellular compartments. This observation raises numerous questions pertaining to fundamental aspects of cell signaling and suggests that cells have spatially compartmentalized signaling hubs. This basic biological insight has clinical implications as well. For example, certain beta-blockers are known to have differential clinical efficacies but the underlying reasons for these differences are not known. We have found that different beta blockers act on distinct hubs of signaling. Beyond their well-established roles in cardiac physiology, adrenergic receptors regulate a wide variety of important physiologically and behavioral processes. We are using our newly developed tools to investigate the consequences of signaling from internal compartments on a range of cellular, physiological, and behavioral outcomes.

UCSF Profiles Page: http://profiles.ucsf.edu/roshanak.irannejad

Tien Peng, M.D.

Developmental pathways in the maintenance of adult tissue homeostasis

Our laboratory is interested in studying how key developmental pathways continue to persist in adulthood to maintain normal homeostatic organ function. We are particularly focused on the mesenchymal cell types (e.g. fibroblasts, pericytes, and etc.) that are poorly understood and lack precise anatomical definition, but are integral to the structural integrity and function of adult organs such as the lung.

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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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Biao Wang, Ph.D.

Research Interests:
Obesity, diabetes, hormones, cAMP, kinase, signaling transduction, transcriptional regulation

Summary:
Type II diabetes mellitus accounts for 90-95% of all cases of diabetes, and this heterogeneous disorder afflicts an estimated 6% of the adult population in Western society. Energy imbalance by high calorie intake and/or lack of physical activity can lead to obesity, which is often associated with an increased risk of developing insulin resistance followed by type II diabetes. Our research is focused on understanding how circulating hormones modulate energy balance in multiple metabolic tissues, and how disruption of these hormonal actions contributes to pathophysiology of type II diabetes.

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Rong Wang, Ph.D.

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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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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David F Teitel, M.D.

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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