Research in my laboratory is primarily focused on elucidating the role of the Hedgehog (Hh) pathway in central nervous system (CNS) development. Hh is a secreted protein that, in both vertebrates and invertebrates, controls patterning and cell type specification in a wide variety of tissues in embryos and adults. Hh functions by stimulating a cascade of responses in cells that ultimately execute cell type specific genetic differentiation programs. In humans, the list of biologically important events that are thought to involve abnormal Hh signalling continues to grow. These include congenital, debilitating malformations of the brain and body, CNS tumors, and cancer. Thus, our work impacts broadly on both basic developmental biological and human health issues.
Previous work in my lab showed that the Gli family of proteins are required mediators of Hh signaling in the developing spinal cord, and function by activating the expression of specific sets of target genes in undifferentiated, multi-potent neural and glial progenitor cells, directing them toward specific fates. Our current research is focused on elaborating the transcriptional mechanisms that function downstream of Hh-Gli signaling to regulate the differential response of cells to this extracellular morphogen. We are also interested in understanding how inputs from other DNA binding proteins are integrated at the transcriptional level to control this process. Another interest in our lab is in uncovering the molecular mechanisms regulating the response of adult spinal cord stem cells to injury.
Our approach to these questions involves a combination of in vivo methods in transgenic mice, embryonic chickens, and adult mouse spinal cord injury models. We also employ various molecular biology techniques including PCR, molecular cloning and mutagenesis, analysis of endogenous gene and protein expression, conditional mutagenesis.