Category: Vascular Biology and Atherothrombosis

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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Priscilla Hsue, MD

Research Interests:
Inflammation, Immunology and Cardiovascular Disease

Summary:
I oversee a multidisciplinary team which is studying the role of inflammation in cardiovascular disease with a focus on HIV. Our work includes descriptions of cardiovascular manifestations in HIV, elucidation of mechanisms underlying this disease process, and proof-of-concept therapeutic interventions to decrease CV risk with potential impact on HIV cure.

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Brian B. Graham, M.D.

Research Interests:

Pulmonary hypertension and pulmonary vascular inflammation, and cardiac angiogenesis.

Summary:

Our research group investigates pulmonary hypertension, a disease of the lung blood vessels. The major focus of our research is how the immune system contributes to the disease. The goal of our work is to discover new treatment approaches to help prevent or reverse this disease.

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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

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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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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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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Takashi Mikawa, M.S., Ph.D.

Research Interests:
Morphogenesis, development, body axis, patterning, cell-to-cell communication, cell architecture, cell fate diversification, cardiovascular system, cardiac conduction system, central nervous system, haemodynamics, growth factor signaling.

Summary:
The establishment of extremely complicated structures and functions of our organ systems depends upon orchestrated differentiation and integration of multiple cell types. Our group focuses to explore a common developmental plan for successful organogenesis, by investigating the mechanisms involved in the differentiation and patterning of the cardiovascular and central nervous systems.

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Michael A Matthay, M.D.

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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Dengke Ma, Ph.D.

Research Interests:

Genetic approaches to understanding physiology and diseases, oxygen-modulated metabolism and behavior; brain-heart-lung interaction and interoception; ischemic disease and tolerance; novel genes and pathways evolutionarily conserved in C. elegans and humans.

Summary:
As humans, we drink when thirsty, eat when hungry, and increase our breathing and heart rates when short of oxygen. How do we (our bodies) know when and how to respond to changes in internal bodily states (e.g. loss of nutrient or oxygen)? Genes and traits that facilitate such underlying mechanisms confer great advantages for animal survival and are strongly selected for during evolution. Using both C. elegans and tractable mammalian model systems, we seek to understand the molecular, cellular and neural circuit basis of how animals sense and respond to changes in internal metabolic and energetic states to elicit behavior and maintain homeostasis. Dysfunction of these fundamental physiological processes leads to many disorders, including obesity, diabetes, neurological and cardiovascular diseases.

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John P Kane, M.S., M.D., Ph.D.

Research Interests:
Structure and function of lipoproteins; genetic determinants of arteriosclerosis

Summary:
The Kane laboratory focuses on the discovery of the native structures of lipoproteins ( proteins that carry cholesterol so that we can better understand how they are involved in the development of heart disease and stroke. We are also active in the discovery of alterations in genes that lead to heart disease and stroke.

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