David Hampson


Brain Development and Neurodevelopmental Disorders

The developing brain follows a strict chronological progression of events that encompasses cellular proliferation, differentiation, and migration.  Brain maturation occurs both prenatally and postnatally and requires precise anatomical and temporal patterns of gene expression and cellular activity.  Perturbations in these events can cause neuropathology.  Autism spectrum disorders (ASD) are the most common neurodevelopmental disorders.  The reported incidence of ASD among newborns has increased dramatically over the past two decades.  Mutations in certain genes are known to cause autistic behaviors such as impaired communication and elevated rates of repetitive behaviors and epileptic seizures.  Examples of genetic disorders with autistic components include Fragile X Syndrome (FXS) caused by mutations in the FMR1 gene, Dravet Syndrome caused by mutations in the NaV1.1 sodium channel, Rett Syndrome caused by mutations in the MECP2 gene, tuberous sclerosis caused by mutations in the TSC1 and TSC2 genes, and a variety of neurological disorders caused by mutations in the SHANK genes.

A major focus of our research is on FXS where we are seeking to carefully document the complete phenotype, and to develop biological therapeutic agents for treating the disorder.  In FXS the protein coded for by the FMR1 gene, Fragile X Mental Retardation Protein (FMRP), is not expressed.  Therefore we use the Fmr1 knockout mouse model of FXS.   Previously we have studied the effects of potential small molecule therapeutic drugs that act at G-protein coupled receptors; specifically, drugs that act on metabotropic glutamate receptors and GABAB receptors.  Using the Fmr1 mouse, our current investigations are directed towards (1) determining the status of myelin (white matter) over the course of brain development and (2) exploring strategies for correcting FXS using viral vector-based biological therapeutic drugs.  For the former, we are assessing the status of glia in the CNS, while in the latter we are constructing and testing the efficacy of adeno-associated viral vectors and lenti viral vectors as a means to replace altered or missing proteins (e.g. FMRP).  Thus, by necessity research in our laboratory requires knowledge in the areas of molecular biology, protein chemistry, neuroscience and neurology, drug delivery, and behavioral pharmacology.

Leslie Dan Faculty of Pharmacy
University of Toronto
144 College Street
Toronto, Ontario, M5S 3M2
Tel: 416-978-4494
Fax: 416-978-8511
Email: d.hampson@utoronto.ca
Website: http://phm.utoronto.ca/hampson/