Brain disorders do not affect every cell or brain region in the same way. The Human Neurobiology Laboratory uses single-nucleus and spatial multi-omic sequencing of human brain tissue to map how gene expression and its epigenetic regulation vary across cell types and anatomical regions. By integrating transcriptomic, chromatin-accessibility, proteomic, and spatial data from the human hippocampus, this work identifies the molecular programs that support neurogenesis and reveals how neuroplasticity, synaptic function, inflammation, and cell survival are disrupted in major depression. This research builds on Prof. Dupont’s longstanding human-tissue studies of hippocampal neurogenesis, aging, depression, and antidepressant-associated cellular changes. By moving from broad tissue-level observations to precise, cell-type- and region-specific mechanisms, the lab seeks to identify candidate therapeutic targets and guide the development of treatments designed to restore healthy brain-cell function.