Research scientists are using cell and animal models to understand the basic mechanisms that cause neurodevelopmental disorders in order to identify therapeutic targets.
We are approaching this problem from many different angles. We believe that increasing our basic knowledge about the mechanisms of disease on multiple biological levels will maximize our ability to succeed in defining mechanisms and identifying new targets for therapeutic remediation. Data from our clinical sciences group informs our basic scientists about how to best model neurodevelopmental disorders. Using a variety of molecular, cellular, physiological, and behavioral techniques, our scientists identify phenotypes that may represent disease pathophysiology in these model systems. We then dissect the molecular mechanisms that cause the phenotypes, and those molecular mechanisms ultimately become therapeutic targets.
Many neurodevelopmental disorders, including schizophrenia, are complex, polygenic disorders. This means that hundreds or even thousands of minor variations in the patient’s genetic code contributed to the patient developing the disorder. To model these polygenic disorders, we generate pluripotent stem cell cultures from a sample of the patient’s skin cells. Our scientists then differentiate these patient-derived stem cells into neurons that represent 2D and 3D models of the human brain. These models inform us about the molecular mechanisms that contribute risk to the development of schizophrenia and other neurodevelopmental disorders, and provide a platform to test whether we can rescue or reverse pathophysiology with novel therapeutics.
Neuroscientists in the Cortical Development Group are studying how cortical circuitry normally forms and functions and how disruption of genes associated with psychiatric disorders negatively impact this process.
LIBD Speaker Series: Dara S. Manoach, Ph.D.
Reduced Sleep Spindles in Schizophrenia: A Treatable Endophenotype that Links Risk Genes to Impaired Cognition Dara S. Manoach, Ph.D. Professor of Psychology, Department of Psychiatry Massachusetts General Hospital, Harvard Medical School Athinoula A. Martinos Center for Biomedical Imaging When: August […]