Category: Site SCVRB


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.

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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

 

 


Andy Chang, Ph.D.

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Research Interests:

Acute oxygen and metabolic sensing in cardiopulmonary regulation and disease

Summary:

To maintain optimal oxygen delivery to tissues, there is constant regulation of respiratory and cardiovascular systems by mechanisms that act on different time scales. On a fast time scale, a small chemosensory organ called the carotid body senses decreases in blood oxygen to increase breathing within seconds. The carotid body can also regulate cardiovascular function acutely, and carotid body hyperactivity contributes to disease progression in hypertension, heart failure, and metabolic syndrome. Using the mouse as our primary model, we aim to identify the molecular mechanisms that mediate the carotid body’s ability to detect changes in blood oxygen as well as other metabolic signals, such as carbon dioxide and acid. One long term goal is to apply this knowledge to manipulating carotid body activity in the treatment of cardiovascular disease and metabolic syndrome.

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Ian Bass Seiple, Ph.D.

 

Seiple

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.

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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.

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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.

UCSF Profiles Page


Biao Wang, Ph.D.

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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.

UCSF Profiles Page


Xiaokun Shu, Ph.D.

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Research Interests:
Protein Rational Design and Directed Evolution for Biology and Medicine

Summary:
We are developing technologies to bridge the gap between clinical medicine and molecular biology. Their successful use in biomedicine will significantly improve treatment of disease.

UCSF Profiles Page


Jeffrey E Olgin, M.D.

Olgin

Research Interests:
Cardiac Electrophysiology, Arrhythmias, Mechanisms, Remodeling, Cardiac Fibrosis, Atrial Fibrillation, Cardiac Ablation, Mouse models, animal models, mouse electrophysiology, optical mapping, atrial fibrillation ablation, clinical trials.

Summary:

Mechanisms of arrhythmias, remodeling and cardiac fibrosis, atrial fibrillation, ventricular fibrillation, sudden death, prediction of atrial fibrillation, prediction of sudden death.
Dr. Olgin’s basic research lab is interested in atrial and ventricular remodeling and how these processes occur to develop a substrate for atrial fibrillation and ventricular tachycardia. His work has demonstrated the circuit for human atrial flutter and has demonstrated the importance of atrial fibrosis as a cause for atrial fibrillation. He is currently interested in how TGFß signaling is regulated in the atria to produce atrial fibrosis and atrial fibrillation. His lab is translational in that he utilizes a spectrum of techniques and studies that span from mouse, large animal physiologic models, human tissue, human biomarkers and genetic approaches to understanding the disease. He also has active studies in understanding the remodeling that occurs in the ventricle in the setting of heart failure and myocardial infarction to create the substrate for sudden death and ventricular tachycardia and fibrillation.
Dr. Olgin also runs the UCSF Cardiology Clinical Coordinating Center. He is PI of the VEST study, a multi-center, international randomized study to determine whether a wearable defibrillator vest can reduce the big early sudden death rate post-MI.

UCSF Profiles Page


Daniel L Minor, Ph.D.

Research Interests:
Membrane proteins; potassium channels, calcium channels

Summary:
Hearts, brains, muscles, and senses require electrical signals to function. We aim to understand the basic cellular components responsible for generating electrical activity. We focus on understanding the structure, function, and regulation of ion channels from a high-resolution viewpoint, understanding how channel mutations cause disease, and on developing new tools for controlling channel function.

Video A Universal CaM Switch Changes the Kv7 Channel

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

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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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Mary J. Malloy, M.D.

 

Research Interests:
Molecular mechanisms in lipoprotein metabolism; genetic basis of metabolic disorders of lipoproteins and of arteriosclerosis

Summary:
My chief research foci are the discovery of previously unknown disorders that affect the metabolism of cholesterol and other lipids, and the discovery of genes that are associated with the risk of heart attack and stroke. Identification of these diseases and genetic markers of risk will lead to improved prevention and treatment of coronary disease and stroke.

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