Gill Center for Biomolecular Science

Phone:

812-856-4998

Email:

carylai@indiana.edu

Department:

Psychological and Brain Sciences

Campus:

IU Bloomington

Education:

• Ph.D. in Biology, University of California, 1988
• B.S. in Biology, California Institute of Technology, 1976

Research interests:

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.

Representative Publications:

• Chen, Y.-J., Zhang, M., Yin, D.-M., Wen, L., Ting, A., Wang, P., Lu, Y.-S., Zhu, X.-H., Li, S.-J., Wu, C.-Y., Wang, X.-M., Lai, C., Xiong, W.-C.-, Mei, L., and Gao, T.-M. (2010) ErbB4 in parvalbumin-positive interneurons is critical for neuregulin 1 regulation of long-term potentiation. Proc Natl Acad Sci (USA) 107:21818-21823.
• Brinkmann, B.G., Agarwal, A., Sereda, M.W., Garratt, A.N., Muller, T., Wende, H., Stassart, R.M., Nawaz, S., Humml, C., Velanac, V., Radyushkin, K., Goebbels, S., Fischer, T.M., Franklin, R. J., Lai, C., Ehrenreich, H., Birchmeier, C., Schwab, M.H., and Nave, K.-A. (2008) Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system. Neuron, 59: 581-595.
• Ghashghaei, H.T., Lai, C. and Anton, E.S. (2007) Neuronal migration in the adult brain: are we there yet? Nat. Rev. Neurosci. 8:141-151
• Ghashghaei, H.T., Weber, J.L., Pevny, L., Schmid, R., Schwab, M.H., Lloyd, K.C., Eisenstat, D.D., Lai, C., and Anton E. S. (2006). The role of neuregulin-erbB4 interactions on the proliferation and organization of cells in the adult subventricular zone. Proc Natl Acad Sci (USA), 103:1930-1935.
• Anton, E.S., Ghashghaei, H.T., Weber, J.L., McCann, C., Fischer, T.M., Cheung, I.D., Gassmann, M., Messing, A., Klein, R., Schwab, M.H., Lloyd, K.C.K. and Lai, C. (2004). Receptor tyrosine kinase ErbB4 modulates neuroblast migration and placement in the adult forebrain. Nat. Neurosci. 7, 1319-1328.
• Michailov, G.V., Sereda, M.W., Brinkmann, B.G., Fischer, T.M., Haug, B., Birchmeier, C., Role, L., Lai, C., Schwab, M.H. and Nave, K.-A. (2004) Axonal neuregulin-1 regulates myelin sheath thickness. Science 304, 700-3.
• Carraway III, K. L., Weber, J. L., Unger, M. J., Ledesma, J., Yu, N., Gassmann, M. and Lai, C. (1997). Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases. Nature 387, 512-516.