University of Kentucky Center for Cancer and Metabolism (Pilot Project - Dr. Teresa Fan)

Cancer remains a leading cause of mortality in the United States, accounting for more than 35% of all deaths despite important preventive and therapeutic successes. Significantly, Kentucky has long been known for disproportionately high incidences of both cancer and metabolic disorders. The emerging recognition that metabolic dysregulation is a hallmark of cancer increasingly points to important roles of metabolic processes and the potential for metabolic modulation to developing novel metabolism-dependent interventions. Thus, there is an urgent need for understanding the mechanisms linking metabolism to cancer development, and for improving treatment that will limit the side effects that impact the quality of life of cancer patients. The University of Kentucky (UK) proposes to establish a unique multidisciplinary Center of Biomedical Research Excellence on Cancer and Metabolism (CCM) to strengthen its cancer research enterprises. The proposed center capitalizes on highly specialized institutional strengths in redox biology, cancer cell signaling and advanced metabolomics instrumentation to focus on underlying mechanisms linking altered metabolism to cancer. To accomplish this goal, we will (1) develop a critical mass of funded investigators with research programs directly related to the Center's unifying theme, (2) provide strong mentoring programs, (3) recruit new investigators to the Center through pilot project grant support that will be leveraged by the institution, and (4) create synergy among research projects that will be leveraged by the existing externally funded centers at the University of Kentucky, including existing COBREs. Becuase metabolomics approaches are data intensive, the CCM will also leverage high-level expertise in biostatistics and bioinformatics to develop promising early-stage investigators well prepared in this exciting new area of cancer research and the emerging importance of data science. Further, the center will develop research cores in metabolism and imaging, which are critical to the proposed studies and will contribute to the development of institutional resources. We have assembled a group of four promising early-stage investigators with basic and translational projects aimed at understanding the role of specific metabolic mediators as contributors to cancer cell survival and invasiveness or as therapeutics that influence specific aspects of cancer cell metabolism. The focus on cancer and metabolism within each project, coupled with a strong mentoring environment in cancer cell metabolism, redox mechanisms, and cell signaling will lay the foundation for the early-stage investigators in the CCM to become independent researchers in cancer research, and be able to incorporate metabolism and data science into the overall approach. Graduates from the CCM will form a cadre of new leaders as mentors or directors of additional core services. Their accomplishments will provide sustained success and stability of the CCM, which will have a major impact on cancer research and metabolic dysregulation. RELEVANCE The Center of Biomedical Research Excellence on Cancer and Metabolism seeks to define mechanisms that support the emerging evidence that links metabolic disorders to cancer. To this end, research support focusing on innovation and translation of ideas from basic research into novel therapy will be provided to junior faculty whose research programs are in this highly significant area. A well-designed and intensive mentoring program and cutting-edge research cores will foster and augment collaborations between project leaders and leading researchers from both within and outside UK.