Category: Muscle Biology and Heart Failure

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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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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Abigail Buchwalter Cool, Ph.D.

Research Interests:
We study the mechanisms that govern the specialization and maintenance of nuclear organization across cell types.

Summary:
We seek to understand how the organization of the cell nucleus is established, specialized across cell types, and maintained over time to influence cellular identity. “Nuclear organization” involves the non-random packaging of the genome within the nucleus, but also the assembly and interactions of other nuclear structures, such as the nuclear lamina and the nucleolus.

This work begins with a particular focus on the nuclear lamina, a nuclear structure that is essential for mammalian development and is mutated in ~15 “laminopathy” diseases that afflict the heart, muscle, bone, fat, and nervous system. We focus on three main thematic areas: (i) defining the essential roles that the nuclear lamina plays in nuclear organization, (ii) exploring disruption of nuclear organization as a possible cellular mechanism of aging, and (iii) determining how nuclear organization is maintained (or alternatively, remodeled) over time.

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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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

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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Rita F Redberg, M.D., M.Sc.

Research Interests:
Summary:
Dr. Rita F. Redberg’s research interests are non-invasive imaging of the coronary arteries comparing transesophageal echo with ultrafast CT and magnetic resonance imaging. Her ongoing research studies include a stray of the role of exercise in heart disease in women. She also does research in exercise echo evaluation of valvular and congenital heart disease as well as the use of transesophageal echo imaging in cardiopulmonary resuscitation.

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Randall J Lee, M.D., Ph.D.

Research Interests:
Arrhythmias, radiofrequency catheter ablation, implantable cardioverter/defibrillators, genetics, gene therapy, tissue engineering, stem cells, cell transplantation, biopolymers, antibodies, myocardial reconstruction/regeneration

Summary:
The research program integrates the disciplines of cell biology, bioengineering and cardiology. A tissue engineering approach is being used to investigate the potential application of cardiovascular reconstruction/regeneration. The use of stem cells and engineered polymer scaffolds are being investigated in heart attach models to determine their usefulness and safety in repairing damaged heart tissue.

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Natalia Z Jura, PhD

Research Interests:
Receptor tyrosine kinases, kinase regulatory mechanisms, membrane proteins, feedback regulation of cell signaling

Summary:
We study basic mechanisms of cellular signaling by Receptor Tyrosine Kinases with a goal to understand how cells receive and process growth signals provided by the neighboring cells and the extracellular milieu. Receptor Tyrosine Kinases are single pass transmembrane receptors that catalyze tyrosine phosphorylation upon activation of their intracellular kinase domains. These receptors are principal regulators of growth and survival signals in cells and therefore frequently become deregulated in human diseases. We are interested in understanding how the kinase activity of these receptors is regulated by ligand binding and how the receptors associate with their regulatory components during the activation process. By combining biochemistry and cell biology we are studying these processes in the reconstituted membrane systems in vitro and in the plasma membrane of the living cells. We also use crystallography to gain an atomic resolution insight into Receptor Tyrosine Kinase regulation that will help us design new approaches for therapeutic intervention.

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Jura Lab Website

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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Guo Huang, Ph.D.

Research Interests:
Comparative study of heart development and regeneration, ischemic heart diseases, stem cell, cardiomyocyte proliferation, regenerative biology

Summary:
The ability to regenerate damaged or lost tissues varies dramatically across organisms and developmental stages. For example, heart regeneration is robust in adult zebrafish and newborn mouse while very limited in adult mouse and human. This presents a particular problem for patients with a heart attack who suffer from a significant loss of heart muscle cells and subsequent life-threatening functional deterioration of the heart.

By taking a comparative approach to study regenerative versus non-regenerative heart repair processes in zebrafish and mouse, we seek to uncover ancestrally conserved injury responses and more importantly, to identify the signals blocking regeneration in the mammalian heart and consequently new treatment strategies for heart diseases.

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