Nitric oxide signaling in healthy and diseased cardiac myocytes

健康和患病心肌细胞中的一氧化氮信号传导

基本信息

批准号：
8011518
负责人：
MARK T ZIOLO
金额：
$ 10.42万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-01-01 至 2013-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8011518
关键词：
Action Potentials Adenoviruses Adrenergic Agents Animals Award Biosensor Cardiac Cardiac Myocytes Cells Cellular biology Collaborations Core Facility Coupling Cyclic GMP Cyclic GMP-Dependent Protein Kinases Data Educational process of instructing Environment Enzymes Functional disorder Funding Goals Heart Heart Diseases Instruction Knockout Mice Learning Mass Spectrum Analysis Measures Mediating Medicine Modification Muscle Cells NOS1 gene NOS2A gene NOS3 gene National Heart, Lung, and Blood Institute Neurons Nitric Oxide Nitric Oxide Synthase Ohio Operative Surgical Procedures Pathway interactions Phosphorylation Physiological Physiology Production Protein Isoforms Proteins Proteomics Public Health Regulation Research Research Support Services Signal Pathway Signal Transduction Small Interfering RNA Techniques Transgenic Mice Universities adrenergic college drug development heart function human NOS2A protein improved innovation novel phospholamban professor response treatment strategy

项目摘要

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.

描述（由申请人提供）：候选人：我是俄亥俄州立大学生理学和细胞生物学系的助理教授。我的部门同样重视研究，教学和服务。因此，我目前有大量的教学干旱服务负荷，这相当于我的努力的约60％。我的短期目标是通过学习新技术并收集新的初步数据来扩展我的研究，以申请额外的多年资金（R01，PPG）。我的长期目标是至少有两种资助的研究线，并成为心脏HNYocytes一氧化氮信号传导领域的公认领导者。环境：OSU医学院极大地支持研究。我的部门为我提供了足够的实验室空间。目前，我在NHLBI R01上是PI，另一个NHLBL R01的共同点是Pi。我有足够的合作机会和我可以完全访问的多个核心功能的机会。奖励后，我将从所有服务和一些教学承诺中撤职，以使我的研究工作加倍。研究计划：该计划包括三个部分，第一部分是我的R01的摘要。第二部分是我想扩展该项目的方式。这种（扩展包括学习新技术（小动物手术<质谱/蛋白质组学），重点是一氧化氮介导的trahslational trahslations修饰后的心脏和心脏疾病的修饰。这些研究将进一步描述硝酸氧化物如何调节的硝酸氧化物对第三部分的调查，该研究是如何调查的，该研究是如何对第三部分进行调查的，该研究是一个独特的研究。氧化诱导的一氧化氮合酶 - 在健康的肌细胞中未表达，我还将学习新技术（创建转基因小鼠，创建NOS2 sirna腺病毒，并创建新的氧化氧化物生物传感器可以确定用于治疗心脏病的药物开发的新目标。此处提出的研究与公共卫生有关，通过可能改善心脏病的治疗方法。