702 North Walnut Grove Ave.
Bloomington, IN 47405-2204
Our lab uses molecular biological approaches to study the nervous system. One major area of interest is the role of neuregulin-ErbB signaling in neuronal and glial function. The neuregulins are a collection of polypeptides that activate a family of transmembrane signaling molecules, the receptor tyrosine kinases known as the “ErbBs.” There is considerable interest in this signaling pathway, as the neuregulin-1 gene has been implicated as a risk factor for the neuropsychiatric disorder schizophrenia. The neuregulin receptor ErbB4 is expressed by multiple populations of migrating neuronal precursors in the developing brain and our studies have helped to show that alterations in ErbB4 function may influence the final placement of these cells. These changes may lead to alterations in brain circuitry, a finding that provides one potential mechanism by which neuregulin-ErbB signaling may contribute to an increased risk for schizophrenia. In addition to this disorder, there is genetic evidence linking specific ErbB4 mutations to amyotrophic lateral sclerosis (ALS) and in animal models of this disease, neuregulin appears to be neuroprotective for motor neurons.
One of the current lab interests is to define the precise molecular role that ErbB4 plays within migrating neuronal precursors. We have adopted a proteomics-based approach to identify the downstream targets and signaling pathways activated by ErbB4. We are currently evaluating multiple candidates that have emerged from this screen. Although our focus has been on its role in the nervous system, it is important to note that ErbB4 is essential for cardiac development and mammary epithelial cell differentiation. In addition, mutations in ErbB4 have been identified as oncogenic drivers for a subset of melanomas. Accordingly, an improved understanding of the signaling pathways activated by ErbB4 may be of significance to a broad range of investigators.