R35HL171542

Cardiovascular potassium channels: from molecular basis to disease therapeutics - abstract

My lab studies the mechanistic basis, and functional consequences, of ion channels, particularly inward rectifier (KIR) and ATP-sensitive (KATP) potassium channels, found throughout the cardiovascular system. Our work integrates studies at multiple levels, from the fundamental molecular basis of channel activity to animal models of pathologies associated with human disease.

We are interested in how channels are constructed and function, how they regulate individual smooth and cardiac muscles, and how altered channel function contributes to the pathological consequences of aberrant function in the cardiovascular system. We have developed the capability to purify and to analyze channel proteins structurally, biochemically and functionally. This allows us to develop and address exciting new questions and hypotheses regarding the fundamental basis of KIR and KATP channel activity.

KATP channels link metabolism to electrical activity in cardiac and smooth muscle and we have discovered how mutations in these KATP channel genes cause distinct human diseases. Cantu syndrome is caused by gain-of-function in vascular KATP channels, and associated with multiple pathological consequences, including reduced systemic vascular resistance, increased cardiac size and output, persistent fetal circulation, pericardial effusion, lymphedema, decreased vascular compliance and decreased gut motility.

Unique cellular and animal models, as well as a unique research clinic, provide the tools for us to explain such features, and to develop appropriate therapies. Our recent work leads us to new hypotheses which will be explored using multiple cell biological and physiological approaches in cells, animals, and humans to reach a full understanding of the nature and role of KATP dependent excitability in regulation of cardiovascular function.

These studies form the background to the development of novel pharmacological approaches and of appropriate specific therapies for KATP-dependent pathologies.

Washington University

TO FOSTER HEART AND VASCULAR RESEARCH IN THE BASIC, TRANSLATIONAL, CLINICAL AND POPULATION SCIENCES, AND TO FOSTER TRAINING TO BUILD TALENTED YOUNG INVESTIGATORS IN THESE AREAS, FUNDED THROUGH COMPETITIVE RESEARCH TRAINING GRANTS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

Saint Louis, Missouri 631101010 United States

Single Zip Code

NHLBI Outstanding Investigator Award (OIA) (R35 Clinical Trial Optional) (RFA-HL-23-004)

Amendment Since initial award the total obligations have increased 191% from $1,088,500 to $3,163,554.