Federal Project Grant Award Summary

Wake Forest University Health Sciences received a $556,484 Project Grant from the National Institute on Drug Abuse (NIDA) under the Drug Use and Addiction Research Programs (CFDA 93.279) awarded June 15, 2026, with a completion date of May 31, 2028. The award funds research to develop cell-type-specific proteomic profiling of microglia—the resident immune cells of the brain—in models of human immunodeficiency virus (HIV) infection and opioid use disorder (OUD). The research employs an innovative Cre-dependent mutant methionyl-tRNA synthetase (MetRS*) system to selectively label nascent proteins in microglia using the noncanonical amino acid azidonorleucine, enabling mass spectrometry-based profiling with unprecedented temporal and spatial resolution across brain regions.

The project will identify distinct and overlapping microglial protein networks that emerge in HIV infection, opioid exposure, and comorbid conditions using echoHIV infection and fentanyl exposure models. By characterizing how HIV and opioid signals converge at the protein level to influence microglial function across disease stages and brain regions, this research addresses a critical gap in understanding the molecular mechanisms underlying more severe neurobehavioral impairments observed in individuals with comorbid HIV and opioid use disorder. The phased R61/R33 design first validates and optimizes the microglial proteomics approach before advancing to comprehensive proteomic characterization and mechanistic studies.