PROJECT SUMMARY The University of Kentucky (UK) Center of Biomedical Research Excellence on Cancer and Metabolism (CCM) was established in March 2017 by a multidisciplinary team of basic and clinical scientists engaged in cutting- edge research on metabolic dysregulations in cancer, an emerging hallmark of disease responsible for tumor development, drug resistance and distant metastasis. The overarching goal of the Phase II CCM is to continue efforts to expand a thematically focused multidisciplinary infrastructure dedicated to defining the contribution of metabolism in the development and treatment of cancer and to use this novel multidisciplinary platform to develop promising project leaders with enhanced skills in an exciting new area of cancer research. With a dedicated team of mentors combining basic and clinical expertise in redox biology, cancer cell signaling, epigenetics, systems biochemistry and clinical trials, as well as core strengths in advanced metabolomics and sophisticated cancer imaging, we will accomplish this overall goal by conducting high-quality basic and translational research addressing metabolic reprogramming governing tumor initiation, metastasis, drug resistance and recurrence. This objective will be met by achieving 2 Specific Aims. Specific Aim 1 is to expand the critical mass of investigators conducting CCM thematic research. We will recruit, coach and solidify the commitment of a cadre of promising project leaders to conduct cancer and metabolism research utilizing a highly effective mentoring system and provide these scientists with cutting-edge research core facilities and services. Proposed new synergies will be developed through 4 well-crafted research projects; an Administrative Core; innovative research cores in metabolism and imaging; strong biostatistics and bioinformatics support; and collaborations with other UK research centers to facilitate the translation of basic findings in cancer metabolism into early therapeutic and/or intervention approaches. Specific Aim 2 is to advance an independent, sustainable, multidisciplinary thematic biomedical infrastructure and research program on cancer and metabolism by strengthening key scientific cores. We propose to expand the scope and capacity of these vital cores by acquiring and installing new state-of-the-art equipment, introducing new technologies and service as well as providing training sessions, workshops and symposiums. Kentucky ranks highest in rates of overall cancer incidence and mortality [1]. In Phase I, the CCM had a transformative impact in career research and retention of the next generation of scientists who address metabolic dysregulations underpinning the causal links between metabolic disorders and cancer development, a major health threat in the nation. Importantly, the Phase II application will build upon these accomplishments to propel CCM to a nationally recognized center in cancer and metabolism research that will also address the region’...