Category: Channels and Arrhythmias


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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Andy Chang, Ph.D.

ChangA

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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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.

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Jason R. Rock, PhD

Rock

Research Interests:
Stem cells in lung development, maintenance, and disease

Summary:
We investigate how the many epithelial and stromal cell types of our lungs are generated during development, maintained for a lifetime and regenerated following injury. To do this, we use in vivo and in vitro models to identify and test the progenitor capacity of putative stem cell populations. We posit that aberrant stem cell behaviors explain many features of common lung diseases such as mucous cell hyperplasia and pulmonary fibrosis. For this reason, we study the molecular mechanisms and environmental influences (i.e., niche) that regulate the division and differentiation of stem cells along various lineages. Our ultimate goal is to identify genetic, molecular and cellular therapies for the treatment of lung disease.

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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.

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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.

Mikawa

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

Lee

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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David J Julius, S.B., Ph.D.

Julius

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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Lily Y Jan, B.Sc., M.Sc., Ph.D.

 

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Research Interests:
Studies of potassium channels

Summary:
Ion channels such as potassium channels and calcium-activated chloride channels are important for the function of the heart, lung, and vasculature. Starting with molecular characterizations of the channel proteins, we try to understand how these channels work and how their activities are regulated under various physiological conditions

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Guo Huang, Ph.D.

Huang

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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