| FACULTYs |
Training
Research Interests Posttranslational modifications, such as phosphorylation and acetylation, play important roles in a variety of cellular processes. Alterations of these modifications may lead to human diseases including cancer. Our lab is interested in how these posttranslational modifications, particularly acetylation, influence biological functions such as gene expression, cell motility etc., in normal and aberrant settings with an emphasis on histone/protein deacetylases (HDACs). Our ultimate goal is to apply our knowledge to cure human diseases. Basic research: Current studies in our lab focus on one of the class II HDACs, HDAC6. HDAC6 is unique within the HDAC family. It has two HDAC domains and deacetylates both histone and tubulin, suggesting it plays important roles in both nuclei and cytoplasm. To study the function of HDAC6 systematically, we plan to purify HDAC6 complex from nuclei and cytoplasm. The outcome of this study will reveal the biological functions of this HDAC. In addition, we also set out to investigate how HDAC6’s enzymatic activities are regulated by upstream signaling. Translational research: Our lab is interested in studying role of HDAC6 and its novel substrate, cortactin, in human cancers, particularly in ovarian and breast cancers. Recently, my lab discovered that SIRT1, a class III HDAC, also deacetylates cortactin and is associated with cell migration. We will further determine whether HDAC6, SIRT1 and cortactin, especially the deacetylated form of cortactin, are involved in ovarian and breast cancer metastasis.
Search
for publications by: Selected publications: Zhang, Y., Zhang, M., Dong, H., Yong, S., Li, X., Olashaw, N., Kruk, PA., Cheng, JQ, Bai, W., Chen, J., Nicosia and Zhang, X. Deacetylation of cortatin by SIRT1 promotes cell migration. Oncogene (accepted for publication) Zhang, X., Yuan, Z., Zhang, Y., Yong, S., Salas-Burgos, A., Koomen, Olashaw, N., Parsons, J.T. Yang, X-J., Dent, S.R., Yao, T-P, Lane, W.S. and T-P, Yao, and Seto, E. (2007) HDAC6 modulates cell motility by altering the acetylation level of cortactin. Mol. Cell. 27, 197-213. Comments in Dev. Cell 13, 161-162 (2007). Zhang, X., Ozawa, Y., Lee H., Wen, Y-D., Tan, T-H, Wadzinski, B.E. and Seto, E. (2005) Histone deacetylase 3 (HDAC3) activity is regulated by interaction with protein serine/threonine phosphatase 4. Genes & Dev. 19, 827-839 Zhang, X., Wharton, W., Yuan, Z., Tsai, S-C., Olashaw, N., and Seto, E. (2004) Activation of the growth/differentiation factor 11 gene by the histone deacetylase inhibitor trichostatin A and repression by HDAC3. Mol. Cell. Biol. 24, 5106-511
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Cancer Biology Ph.D. Program H. Lee Moffitt Cancer Center, MRC-4 East 12902 Magnolia Drive Tampa, Florida 33612 Phone: 813-745-6876 E-mail: CancerPhD@moffitt.org Copyright © 2008 University of South Florida |
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