Lauren Wills, PhD

Drugs of abuse—including stimulants, opioids, cannabinoids, nicotine, and alcohol—exert profound and lasting effects on brain function, behavior, and immune regulation. While much research has centered on their actions in canonical reward pathways, there is increasing recognition that these substances also engage diverse cell types and circuits across brain regions involved in aversion, motivation, and neuroimmune surveillance. However, our understanding of how drugs of abuse reshape the brain’s transcriptional landscape at single-cell resolution remains incomplete. My research leverages cutting-edge single-cell and spatial transcriptomics to uncover how addictive substances reprogram specific neuronal and glial populations across brain regions implicated in addiction, including the nucleus accumbens, habenula, and prefrontal cortex. Using technologies such as STARmap, Visium, and Xenium, we are mapping gene expression changes in situ with spatial and cell-type specificity. This work is further contextualized by models of HIV infection, allowing us to explore how viral persistence and neuroimmune activation interact with substance use to exacerbate vulnerability. Through NIH-funded studies and interdisciplinary collaborations, we integrate these high-dimensional datasets with behavioral models and neural circuit mapping to dissect the molecular and cellular architecture of drug-induced brain plasticity. The long-term goal of this research is to identify convergent transcriptional programs and cell populations that drive maladaptive behaviors and represent new targets for therapeutic intervention across multiple substance use disorders.