Ronald Hart

Our goal is to identify neuronal mechanisms underlying multiple disorders by using genetically-defined human stem cells to prepare mixtures or “villages” of cultured neurons.  We have made hundreds of stem cell lines from individuals with genetic risk for alcohol use disorder, schizophrenia, or bipolar disease for parallel projects.  The neuron villages are process for single-cell RNA sequencing and epigenetic chromatin assays to link genetic variants with altered cellular mechanisms.  These experiments generate large amounts of data to identify genes, measure each in individual cells, and use sequence variants to match individual neurons to human donors.  Using bioinformatic analysis, we then link altered cellular pathways with genetic variants.  In the case of schizophrenia, for example, we will analyze several rare genetic variants that are quite distinct from each other, yet all cause the same symptoms.  We believe that the effects of different genetic variations will converge on similar biochemical pathways underlying disease.