Category: Muscle Biology and Heart Failure

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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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

Arthur Weiss, M.D., Ph.D.

Research Interests:
Cell Surface Molecules and Molecular Events Involved in Lymphocyte Activation

Summary:
Dr. Weiss studies on how the functions of cells of the immune system are regulated. The immune system protects individuals from infections and malignancies. However, it is also involved in undesirable destructive responses, such as in autoimmune and allergic diseases as well as atherosclerosis and transplant rejection.

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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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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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Michael J Mann, M.D.

Research Interests:
1. Molecular/cellular biology and molecular genetics of atherosclerosis and heart failure. 2. Development of hybrid surgical and molecular/cellular therapies for heart disease. 3. Stem and progenitor cell transplantation for cardiovascular regeneration. 4. Cardiovascular tissue engineering. 5. Reduction to clinical practice of current methods in genetic, molecular and cellular disease intervention. 6. Novel targeted molecular therapies for lung cancer. 7. Molecular profiling of cancers for personalized medicine. 8. Development of novel methods of in vivo/ex vivo gene therapy and gene transfer. 9. Novel approaches to therapeutic neovascularization for coronary and peripheral ischemic disease. 10. Cardiovascular cell cycle biology. 11. Myocardial gene therapy.

Summary:
Dr. Mann’s research focuses on the molecular and cellular biology of heart disease with an emphasis on practical ways to develop new treatments for heart failure. These involve potential gene and molecular therapies, combinations of molecular and cell-based treatments with surgical reconstruction, and evaluation of novel materials for the development of bioartificial replacements of lost or damaged heart tissue.

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