PROJECT SUMMARY/ABSTRACT This proposal outlines a comprehensive five-year physician-scientist career development plan for Dr. Alice K. Min. Dr. Min is a third-year Infectious Diseases Fellow in the American Board of Internal Medicine Research Pathway Residency/Fellowship in Infectious Diseases at the Icahn School of Medicine at Mount Sinai. Her research focuses on HIV-1 associated neurocognitive disorders (HAND), specifically investigating the role and function of the endocannabinoid system (ECS) that has well-established anti-inflammatory properties through activation of cannabinoid receptors type 1 (CB1R) and type 2 (CB2R). Her study proposes that CB2R agonism reduces neuroinflammation associated with HAND, which currently lacks effective therapies despite affecting up to 50% of people with HIV-1 (PWH). Findings from this study will enhance our mechanistic understanding of the anti-inflammatory properties of CB2R in central nervous system (CNS) HIV-1 infection and can lead to novel therapeutic paradigms for HAND in PWH. This K08 award will provide Dr. Min with advanced training in the following areas: 1) To develop as an HIV virologist with her own laboratory by taking advantage of the unparalleled expertise of faculty and fellows at Mount Sinai and collaborators; 2) To communicate, interact, and collaborate with research colleagues in HIV studies and infectious diseases, in the United States and around the world; 3) To devote 20-25% of her efforts towards developing skills and knowledge as a clinician in infectious diseases; and 4) To develop preliminary data that will serve as the foundation for a future R01 that will support transition to research independence. To achieve these goals, Dr. Min has assembled a multidisciplinary mentor team. Dr. Talia H. Swartz, her primary mentor, is a successful physician-scientist whose expertise is in pro- inflammatory comorbidities associated with chronic HIV-1 infection. Her co-mentors are Dr. Benjamin K. Chen, a renowned HIV-1 virologist and pioneer in HIV-host cell interactions, and Dr. Schahram Akbarian, a distinguished neuroscientist specializing in epigenomic and epitranscriptomic technologies using mouse models. An additional scientific advisory committee composed of highly regarded principal investigators in the fields of stem cell biology, molecular neuroscience, neuropathology, and NeuroHIV will provide additional guidance. Her mentors and advisory team will guide Dr. Min throughout her training. The proposed experiments and didactics outlined in this proposal will position Dr. Min with a unique set of interdisciplinary skills and resources that will enable her to transition to independence as a physician-scientist specializing in NeuroHIV. Dr. Min is firmly committed to a career in translational NeuroHIV research and is strongly supported in her career and research goals by her mentors and her division at the Icahn School of Medicine at Mount Sinai.