Mentoring the next generation of substance use, HIV, and epigenetic researchers.

Dr. Annesa Flentje mentors early career researchers, focusing on substance use, stress, and epigenomic markers of substance use. Substance use increases in the presence of stress. Further, unique molecular profiles of both substance use and stress have been observed, suggesting that alterations in the epigenome may serve as biological markers for substance use. Unfortunately, research to date is limited because these models have not explicitly compared people living with HIV (PLWH) and people living without HIV (PLWoH). Further, unique hormonal exposures that occur in humans that have been unaccounted for in research investigating substance use and potential epigenetic biomarkers for substance use and these hormonal exposures may also be related to alterations in the epigenome. This project will expand Dr. Flentje’s research program to integrate hormonal exposures and HIV status, to be able to identify epigenomic markers of substance use in the presence of endogenous and exogenous hormone exposures comparing PLWH to PLWoH. To support expansion of her research, Dr. Flentje will receive additional training in HIV, hormone exposures, dominance analysis, and epigenetic bioinformatics analysis. This K24 will support Dr. Flentje in mentoring patient-oriented researchers in health research who will leverage survey and epigenetic data from existing cohort studies: a community based longitudinal study, the MACS/WIHS Combined Cohort Study, and the All of Us Research Program to 1) understand key stress predictors of substance use and compare the relative strength of these predictors between PLWH and PLWoH; 2) identify endogenous and exogenous hormonal predictors of substance use among people and determine differences in the relative strength of these predictors among PLWH and PLWoH; and 3) derive stress, substance use, and hormonal phenotypes, identify epigenetic markers of these phenotypes, and identify differences in these epigenetic markers between PLWH and PLWoH. This K24 will support mentorship of early career researchers focusing on substance use, HIV, hormonal biology, epigenomics, and stress. It will also expand Dr. Flentje’s mentorship skills to integrate structures to support mentees in navigating financial challenges, loan repayment applications, family building, and emotional hardships. As substance use research and epigenomic research is an emerging area of study, a national approach to mentorship to promote innovation in patient-centered research is critical.