Affiliations

Professor, Psychiatry and Biobehavioral Sciences

My laboratory studies the effects of the reelin signaling pathway in regulating cell migration during embryonic development. Reelin signaling is initiated by the secretion of reelin, a large extracellular matrix protein, from a variety of different cell types. Reelin interacts with two different receptor systems, the ApoER2/VLDLR low-density lipoprotein receptors, and alpha3/beta1 integrin. Stimulation of the receptors induces phosphorylation of the intracellular adaptor protein Dab1, which then initiates a cascade of events ultimately interacting with the cytoskeleton. We examine reelin signaling and its effects in the developing brain and spinal cord, as well as in the developing mammary gland. Reelin signaling has been widely recognized for a role in shaping layered structures in the brain, including the cortex, hippocampus, and cerebellum. Mutations in reelin have also been linked with a variety of neurodevelopmental disorders such as schizophrenia and autism. We are currently examining how reelin signaling might be affected in neurodevelopmental disorders, and particularly how environmental factors, such as maternal stress or pesticide exposure can interact with the reelin signaling pathway. Our studies involve behavioral analysis of our animal models, along with characterization of anatomical changes occurring in the brain. Although reelin?s role in the brain is well established, there has been little research on the effects of reelin signaling in other parts of the central nervous system. We have identified several unique loci of expression of the reelin signaling pathway and are currently characterizing both the expression of pathway components in these regions and the effects of disrupting reelin signaling on these areas. Reelin also has roles outside the central nervous system and we have recently established that intact reelin signaling is required for normal mammary gland development. In the mammary gland, reelin regulates the migration of mammary epithelial cells, and we are currently characterizing the impact of disrupting reelin signaling on these cells. Reelin signaling appears to be reduced or absent during metastatic breast cancer, so we hope to identify how changes in reelin signaling might contribute to the invasiveness of breast cancer cells.