Federal Grant Award Summary

The National Institute on Drug Abuse awarded Icahn School of Medicine at Mount Sinai a $2.352 million Project Grant under the Drug Use and Addiction Research Programs (CFDA 93.279) to conduct single molecule functional validation of neurogenomic alterations in opioid-exposed HIV-affected brains. The award, effective February 15, 2026 through January 31, 2030, supports two primary research objectives: (1) single molecule validation of prior single cell research findings through fiber-sequencing analysis of brain tissue from the SCORCH (Single Cell Opioid Response in the Context of HIV) Consortium cohort, examining nucleosome positioning, DNA methylation patterns, and transcription factor footprints in cingulate cortex samples; and (2) functional validation through HIV-induced lineage tracing studies in human induced pluripotent stem cell-derived neuron-astrocyte-microglia tricultures combined with CRISPR-based microglial promoter repression targeting dysregulated genes identified in postmortem brain tissue.

The research addresses the critical intersection of HIV infection and opioid use disorder comorbidity, investigating the molecular environment within the brain that permits HIV viral replication and cytotoxic damage despite systemic antiretroviral drug suppression. By integrating multiomic fiber-sequencing data with existing single cell RNA and ATAC-sequencing datasets, the project aims to provide comprehensive neurogenomic insights into disease mechanisms underlying substance use and HIV co-infection, advancing knowledge relevant to prevention, diagnosis, and treatment approaches for individuals living with both conditions.