South Carolina COBRE in Oxidants, Redox Balance and Stress Signaling

总体-摘要 在第三阶段COBRE的支持下，南卡罗来纳州氧化剂、氧化还原平衡和压力信号中心 （氧化还原COBRE）在南卡罗来纳州（MUSC）医科大学将完成其过渡到长期 可持续性作为氧化还原病理学的国家竞争力的多学科研究计划。期间 在第一和第二阶段，我们的Redox COBRE成功地努力（i）扩大了受资助的 MUSC的研究人员研究了氧化还原途径和代谢功能障碍在各种疾病中的因果作用， 人类病理学（癌症、心血管和神经退行性疾病、糖尿病、胃肠道 （二）开发先进的科学核心资源，提供广泛的 研究氧化应激的生物学显著影响的能力。我们目前的核心成员 包括44名高级和初级教师，自2009年以来已获得超过5100万美元的奖励。 方案的开端。到目前为止，Redox COBRE已经指导了20名目标教师（初级研究员+ 试点项目支持的PI）。在这些人中，有10人获得晋升，16人被保留在我们的 机构。作为一个群体，这些教师已经发表了250多篇同行评议的论文，并获得了 56个校外补助金（包括31个NIH赠款（PI角色），其中16个是R 01补助金，8个是SBIR/STTR- 支持创业）。第三阶段建议的主要组成部分是：（1）行政核心， 组织、协调、财政和问责职能;（2）分析性氧化还原核心， 用于定量氧化还原敏感分子丰度和基于氧化还原的分析生物化学服务 细胞内稳态的变化;（3）蛋白质组学核心，提供最先进的质谱（MS）， MS成像能力;（4）细胞和分子氧化还原成像核心，提供基于细胞和组织的 共聚焦、多光子和超分辨率显微成像;以及（5）试点项目计划（PPP）， 利用中心资源促进研究工作，并促进与Redox COBRE的合作 成员朝着我们的目标，成为一个独立的中心氧化还原生物学和信号（简称 到“氧化还原中心”），我们将在我们的实质性科学和机构成就的基础上：（目标1） 提高我们的科学核心的功能和效率，实现最佳定位，以服务中心 主题和转化目标，并实现/保持可持续性;（目标2）利用公私伙伴关系发展中心 成员资格，并促进翻译氧化还原信号研究在人类背景下的重要性， （目标3）开发研究组合以及Redox COBRE与其他IDEA之间的联系 计划，以建立自己作为一个国家的存在凝聚各种学科和专业领域。 因此，我们正在寻求建立一个长期成功的战略地位，作为一个新兴的，大学- 指定的氧化还原中心，这将是为数不多的国家资源之一，为调查人员利用或开发新的 针对病理性氧化还原途径的技术、疗法和干预措施。

Overall – Abstract With Phase III COBRE support, the South Carolina Center in Oxidants, Redox Balance, and Stress Signaling (Redox COBRE) at the Medical University of South Carolina (MUSC) will complete its transition to long-term sustainability as a nationally competitive multidisciplinary research program in redox pathobiology. During Phases I and II, our Redox COBRE was successful in its efforts to (i) expand the critical mass of funded investigators at MUSC studying the causal role of redox pathways and metabolic dysfunction in a wide range of human pathologies (cancer, cardiovascular and neurodegenerative diseases, diabetes, gastrointestinal disorders and drug addiction) and (ii) develop advanced scientific core resources offering a broad range of capabilities for investigating the biologically significant effects of oxidative stress. Our current core membership comprises 44 senior and junior faculty members that have received more than $51 million in awards since the program’s inception. To date, the Redox COBRE has mentored a total of 20 target faculty (junior investigators + pilot project-supported PIs). Of these individuals, 10 have been promoted and 16 have been retained at our institution. As a group, these faculty members have published more than 250 peer-reviewed papers and secured 56 extramural grant awards (including 31 NIH grants (PI role) of which 16 are R01 awards and 8 are SBIR/STTR- supported start-ups). The major components of this Phase III proposal are: (1) an Administrative Core providing organizational, coordinating, fiscal and accountability functions; (2) an Analytical Redox Core delivering analytical biochemistry services for quantification of redox-sensitive molecule abundance and redox-based changes in cellular homeostasis; (3) a Proteomics Core that offers state-of-the-art mass spectrometry (MS) and MS-imaging capabilities; (4) a Cell & Molecular Redox Imaging Core that provides cell and tissue-based confocal, multiphoton and super-resolution microscopic imaging; and (5) a Pilot Projects Program (PPP) that fosters research endeavors utilizing Center resources and facilitates collaborations with Redox COBRE members. Towards our objective of becoming a stand-alone Center of Redox Biology and Signaling (abbreviated to “Redox Center”), we will build upon our substantial scientific and institutional achievements, to: (Aim 1) enhance the function and efficiencies of our scientific cores, achieving optimal positioning to serve Center thematic and translational goals and achieve/ maintain sustainability; (Aim 2) leverage the PPP to grow center membership and promote the importance of translational redox signaling research in the context of human disease; (Aim 3) develop the research portfolio and connections between the Redox COBRE and other IDeA programs to establish ourselves as a national presence coalescing various disciplines and areas of expertise. Thus, we are seeking to establish a strategic position for long-term success as an emergent, University- designated Redox Center that will be one of few national resources for investigators to utilize or develop new technologies, therapeutics and interventions targeting pathological redox pathways.