Wu, Lai-Chu

Lai-Chu Wu, M.D., Ph.D.

Associate Professor
Department of Internal Medicine

Joint Appointment
Department of Molecular Virology, Immunology and Medical Genetics
Department of Molecular and Cellular Biochemistry

Research Interests:

Generation of immune diversities, transcription regulation, and the molecular events of tumorigenesis.

Research Summary:

We are studying the mechanism that regulates somatic V(D)J recombination, which generates a diversity of antibodies and T cell receptor genes. This process is the only site-specific DNA rearrangement events in vertebrates and any errors may lead to genetic instability and mutations. In particular, we are studying the structure and function of a family of large zinc finger transcription factors, which may link transcription to somatic recombination. These proteins are also important in mediating specific gene expression. Our study is fundamental to understand the generation of immune diversities, transcription regulation, and the molecular events of tumorigenesis.\

Selected Publications:

Wu L.C., Morley B.J., Campbell R.D. (1987) Cell-specific expression of the human complement protein factor B gene: Evidence of the role of two   distinct 5'-flanking elements. Cell 48, 331-342.

Helmsoe, I., Allen, C. E., Cohn, M., Tulchinsky, E. and Wu, L.C. (2000) The kappa B and V(D)J recombination signal sequence binding protein KRC regulates transcription of the mouse metastasis associated gene mts1. J. Biol. Chem. 275, 913-920.

Hicar, M., Robinson, M., Muthusamy, R., and Wu, L. C. (2000) Developmental expression of the recognition signal sequence binding protein KRC is consistent with a role in VDJ recombination. FASEB J. 14: (6) A919.

Allen, C. E. and Wu, L. C, (2000) Downregulation of KRC induces proliferation, anchorage independence, and mitotic cell death  in HeLa cells. Exp. Cell Res. 260, 346-356.

Hicar, M. D., Liu, Y., Allen, C. E., and Wu, L. C. (2001) Structure of the Human Zinc Finger Protein KRC: Molecular Cloning, Expression, Exon-Intron Strcture, and Comparison with Paralogous Genes HIV-EP1 and HIV-EP2. Genomics, 71, 89-100.

Cohn, A. M., Hjelmsoe, I., Wu, L. C., Guldberg, P. Lukanidin, E. M., and Tulchinsky, E. M. (2001) Characterization of Sp1, AP-1, CBF, KRC binding sites and minisatellite DNA as functional elements of the metastasis-associated mts1/S100A4 gene intronic enhancer.  Nucleic Acids Res. 29, 3335-3346.

Wu, L.C., Hicar, M.D., Hong, J-w., and Allen, C.E. (2001) The DNA-binding ability of HIVEP3/KRC decreases upon activation of V(D)J recombination. Immunogenetics, 53, 564-571.

Hicar, M.D., Robinson, M. L., and Wu, L. C. (2002) Embryonic Expression and Regulation of the Large Zinc Finger Protein KRC. Genesis, 33, 8-20.

Oukka, M., Kim, S. T., Lugo, G., Sun, J., Wu, L. C., and Glimcher, L. (2002) The transcription factor KRC regulates TNF receptor-driven responses through interaction with TRAF2. Molecular Cell, 9, 121-131.

Wu, L.C. (2002) ZAS: C₂H₂ zinc finger proteins involved in growth and development. Gene Expression, 10, 137-152.

Allen, C., Mak, C. H., and Wu, L.C. (2002) The kB transcriptional enhancer motif and signal sequences of V(D)J recombination are targets for the zinc finger protein HIVEP3/KRC: a site selection amplification binding study. BMC Immunology 2002, 3:10.

Allen, C.E., Muthusamy, R., Wesibrode, S. and Wu, L.C. (2002) Developmental anomalies and neoplasia in animals and cells deficient in the large zinc finger protein KRC. Genes Chromosomes and Cancer, 35:287-298.

Hong, J-W, Allen, C. E., and Wu, L.C. Inhibition of NF-kB by ZAS3, a zinc finger protein that also binds to the kB motif. Proc. Natl. Acad. Sci (in press)