Brady Maher PhD
Associate Professor of Psychiatry and Behavior Sciences
Associate Professor of Psychiatry and Behavior Sciences
My lab is interested in understanding the cellular and circuit pathophysiology that underlies neurodevelopmental and psychiatric disorders. Recent progress in clinical genetics has led to the identification of genetic variation and genes that are associated with these disorders. However, information about the function of many of these genes during neurodevelopment and in the adult brain is lacking. My group focuses on trying to understand the function of these risk genes by manipulating their expression level in utero during the peak of cortical development. We then use a variety of approaches and technologies to identify resulting phenotypes and molecular mechanisms including cell and molecular biology, optogenetics, imaging, and electrophysiology.
Current projects in the lab are focused on understanding the function of transcription factor 4 (TCF4), a clinically pleiotropic gene. Genome-wide association studies have identified genetic variants of TCF4 that are associated with schizophrenia. Autosomal dominant mutations in TCF4 result in Pitt Hopkins syndrome, a rare neurodevelopmental disorder with a variety of symptoms including severe intellectual disability, developmental delays, absent speech, and breathing abnormalities. Using our model system we have identified several interesting electrophysiological and cell biological phenotypes associated with altering the expression of TCF4 in utero. We hypothesize that these phenotypes represent cellular pathophysiology related to these disorders and by understanding the molecular mechanisms responsible for these phenotypes we expect to identify therapeutic targets for drug development.