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.

Overall – Narrative While oxygen provides the most efficient way to produce energy through oxidative phosphorylation, paradoxically it also produces toxic byproducts. Through adaptation, organisms have evolved numerous redox based stress pathways to counteract this toxicity. In human diseases, these pathways can sometimes malfunction leading to a broad range of human maladies. This COBRE seeks to support faculty and their research in these areas with an agnostic viewpoint on the choice of disease. Our overall goal continues to be to build a sustainable Center that can provide a focal effort to comprehend the integral importance of redox stress signaling in human diseases and the treatment thereof.