Single Cell PTSD: Novel Target Identification

forthcoming

Post-traumatic stress disorder (PTSD) is a devastating psychiatric disease triggered by severe psychological trauma, affecting 4% of the global population - a prevalence projected to rise due to ongoing conflicts like the war in Ukraine and the looming threat of climate change. Despite its widespread impact, we lack effective treatments of PTSD, placing a significant burden on individuals and society. Previous PTSD research was hindered by limitations such as bulk tissue analyses, a lack of epigenetic focus, or small sample sizes. These drawbacks limit our understanding of cell-type-specific alterations during PTSD. My proposed project will leverage single-nuclei RNA sequencing, DNA methylation profiling, and 3D chromatin structure analysis to achieve unprecedented insights into PTSD pathology. Specifically, I aim to: 1) Identify cellular, epigenetic, and transcriptional perturbations in a post-mortem human brain PTSD cohort, revealing promising molecular targets. 2) Characterize classical models of PTSD using single-nuclei genomics, and develop novel humanized model of PTSD. This will enable the identification of the most relevant model for human PTSD, and streamline further validation of targets. 3) Test the efficacy of novel as well as already identified targets from my pilot animal study by utilizing epigenome-modifying tools to alleviate PTSD pathology in mouse models. This project will deepen our understanding of PTSD at unprecedented resolution, ultimately validating novel molecular targets and paving the way for more effective interventions in future.