PROJECT SUMMARY/ABSTRACT African American men (AAM) disproportionately experience the burden of prostate cancer with a mortality rate approximately 2.4-fold greater than that observed among white men in the U.S. This represents the single largest known cancer disparity by race in the U.S., and it may reflect both biologic heterogeneity in the cancers that arise in AAM, as well as differences in socioeconomic factors that influence healthcare utilization. The relative contribution of sociocontextual and biologic factors to prostate cancer disparities remains unclear. Prostate cancers are phenotypically and molecularly heterogeneous, and a better understanding of tumor subtypes by race may aid in the understanding of disease etiology and disparities. Preliminary evidence suggests that low grade tumors in AAM have a higher propensity for progression. The identification of intrinsic subtypes in other cancers, such as breast cancer, has had profound implications for our understanding of the underlying biology and clinical management of those cancers. I hypothesize that the clinical management of prostate cancer can be further optimized for AAM with further understanding of molecular tumor heterogeneity. I will leverage transcriptomic and clinical data from the Men of African Descent and Carcinoma of the Prostate Network and GenomeDx Decipher Genomic Resource Information Database™ to investigate molecular tumor subtypes with respect to prostate cancer disparities. To that end, I will: 1) characterize the PAM50 subtypes in prostate cancer by self-identified race/ethnicity and assess their prognostic value; 2) use tumor transcriptomic data to derive, validate, and characterize novel prostate cancer subtypes among AAM; 3) assemble a retrospective cohort of AAM with low-grade prostate cancer to identify molecular predictors of tumor progression. These research aims are supported by a comprehensive training plan tailored to my training goals: 1) developing an applied knowledge of advanced concepts in prostate cancer biology, epidemiology, and disparities, and 2) developing a bioinformatic and computational biology skillset. This research and training plan will provide me with the skill set to establish a career as a leader in molecular prostate cancer epidemiology and disparities research. To help me accomplish these goals, I will receive guidance from a team of experts in molecular prostate cancer research, who will help expand my knowledge of prostate cancer epidemiology, disparities, biology, pathology, clinical management, and methods for tumor molecular profiling. With the support of my mentor, Advisory Panel, and the rich training environment of Dana-Farber Cancer Institute, this award will help facilitate my transition to research independence.