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Nitric oxide signaling in healthy and diseased cardiac myocytes

$104,166K02FY2009HLNIH

Ohio State University, Columbus OH

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Abstract

DESCRIPTION (provided by applicant): Candidate: I am an assistant professor in the Department of Physiology and Cell Biology at the Ohio State University. My department equally values research, teaching, and service. Thus, I currently have a substantial teaching arid service load, which equates to ~60% of my effort. My short-term goals are to expand my research by learning new techniques and to gather new preliminary data to be used to apply for additional multi-year funding (R01, PPG). My long-term goals are to have at least two funded lines of research and to be a recognized leader in the field of nitric oxide signaling in cardiac hnyocytes. Environment: The College of Medicine at OSU greatly supports research. My department has provided me with adequate lab space. Currently, I am PI on a NHLBI R01 and a Co-l on another NHLBl R01. There are ample opportunities for collaboration and multiple core-facilities to which I have full access. Upon award, I will be removed from all service and some teaching commitments to double my research efforts. Research Plan: this plan consists of three sections, the first section is a summary of my R01. the second section is how I would like to expand this project. This (expansion consists of learning new techniques (small animal surgery<mass spectrometry/proteomics) focusing on nitric oxide-mediated post trahslational modifications in healthy and diseased cardiac mybcytes. These studies will further delineate how nitric oxide regulates cardiac myocyte function, the third section is a distinct, new line of research for my lab. We propose to investigate an isoform that produces nitric oxide, inducible nitric oxide synthase-NOS^ Which is not expressed in healthy myocytes. For this section, I will also learn new techniques (creation of transgenic mice, creating a NOS2 siRNA adenovirus, and creating a novel nitric oxide biosensor). Using these innovative techniques we will be able to provide a new integrated understanding of how NOS2 expression modulates cardiac myocyte function. These results may identify new targets for drug development and strategies for the treatment of heart diseases. RELEVANCE (See instructions): Nitric oxide is an important regulator of heart function, the production of nitric oxide is altered in many cardiac diseases leading to dysfunction of the heart. The studies proposed here are relevant for public health by potentially improving the treatment of heart diseases.

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