mlesortDr. Mathieu Lesort, Assistant Professor in the Department of Psychiatry and Behavioral Neurobiology, is leading a pilot study supported by the Department to test the hypothesis that selective and developmentally regulated post translational modifications of the Disrupted InSchizophrenia-1 gene (DISC1) tightly regulate its association with binding proteins. Schizophrenia and schizoaffective disorder are common and devastating diseases of the brain that remain poorly understood and likely result from a complex interplay between multiple factors influencing susceptibility and progression.  

Since the causes and pathogenesis of schizophrenia remain unknown, the best strategy is to characterize the cellular mechanisms by which known risk genes may intersect with the pathology.  Of these risks, genetic variations of DISC1 were found to segregate with mental illnesses including schizophrenia, schizoaffective disorder, recurrent major depression, and adolescent conduct disorder.  Genetics, clinical, and cell biology studies have provided evidence that DISC1 may be a key piece of the schizophrenia puzzle.  Our understanding of the cellular role of DISC1 has been accelerated through identifying its protein interacting partners and examining their functional significance.  These protein interaction studies have provided evidence that most functions ascribed to DISC1 are largely based on inferences from the know functions of the proteins that interact with DISC1.  While analysis of the DISC1 interacting protein network is increasingly serving as tools to unravel the molecular basis of schizophrenia and schizoaffective disorder little is known on the mechanisms that regulate the DISC1 protein interactome.  Results from these studies will contribute to understanding the role of DISC1 in mental illnesses.