In this seminar Dr. O’Roak will highlight his lab’s recent work using deep mutational scanning to understanding genotype-phenotype relationships for PTEN-related disorders. In addition, he will present unpublished work leveraging single-cell genomics and induced pluripotent stem cells to model human cortical development in vitro.  

Dr. O’Roak’s research focuses on the molecular basis of neurodevelopmental disorders (NDDs). His pioneering work in the last decade has focused on developing and implementing new research paradigms and technologies that challenge the genetic intractability of complex NDDs, especially autism spectrum disorder (ASD). Through these studies, and similar efforts by others, ~100 different genes are no longer merely ‘candidate’ genes for ASD risk, but are now ‘known’ genes based on their recurrent disruption by de novo mutations.  In addition to his gene discovery efforts, Dr. O’Roak is developing a paradigm that incorporates many different patient-specific mutations in a multitude of models with complementary strengths and weaknesses. Advances in genome editing, induced pluripotent stem cells (iPSCs), neurogenetics, and functional genomics have made this approach feasible. Dr. O’Roak studies mutations in genes that are master regulators of key biologic networks to provide an avenue for reducing the phenotypic complexity of autism, biomarker discovery, and targeted personalized therapies.