Phone: (303) 724-4051
Transcriptional regulation governs a broad spectrum of cellular activities: cell cycle progression, cell migration, apoptosis, or metabolism. We are interested in elucidating the molecular mechanisms underlying transcriptional regulation in response to physiological and pathological signals. Particularly, our research over the past decade has focused on CtBP, a transcriptional co-repressor, and has uncovered a unique function of this protein as a redox-sensor in transcription control. This function allows cells to couple the metabolic status with gene expression. Furthermore, we demonstrate that CtBP is subjected to post-translation modifications in response to cellular stress and, consequently, triggering apoptosis independent of p53. Both aspects of our research have important therapeutic implications in human diseases. The ultimate and long-term goal of my lab is to develop drugs against metabolic disorders and cancers based upon molecular details as revealed by basic research.
Recent Selected Publications:
Zhang, Q., D. W. Piston, and R. H. Goodman. Regulation of corepressor function by nuclear NADH. Science. 2002 295:1895-7.
Zhang, Q. *, Y. Yoshimatsu, J. Hildebrand, S. M. Frisch, and R. H. Goodman. Homeodomain interacting protein kinase 2 promotes apoptosis by downregulating the transcriptional corepressor CtBP. Cell 2003 115:177-86. *corresponding author
Grooteclaes M., Q. Deveraux, J. Hildebrand, Q. Zhang, R. H. Goodman, and S. M. Frisch. C-terminal-binding protein corepresses epithelial and proapoptotic gene expression programs. Proc. Natl. Acad. Sci. U S A. 2003 100:4568-73.
Zhang, Q. *, Fjeld, A. C., Nottke, A. C., and Goodman, R. H. 2005a in CtBP family proteins (Chinnadurai, G., ed), Landes Bioscience, TX *corresponding author
Zhang, Q., A. Nottke, and R. H. Goodman. Homeodomain interacting protein kinase 2 mediates CtBP phosphorylation and degradation in UV-triggered apoptosis. Proc. Natl. Acad. Sci. U S A. 2005b 102:2802-7.
Zhang, Q. *, S. Y. Wang, A. C. Nottke, J. V. Rocheleau, D. W. Piston, and R. H. Goodman*. Redox senspr CtBP mediates hypoxia-induced tumor cell migration. Proc. Natl. Acad. Sci. U S A. 2006 103:9029-33. *corresponding author
Wang, S. Y., M. Iordanov, and Q. Zhang*. C-Jun NH2-terminal kinase promotes apoptosis by down-regulating the transcriptional co-repressor CtBP. J. Biol. Chem. 2006 281:34810-5
Zhang, Q. *, S. Y. Wang, C. Fleuriel, D. Leprince, J. V. Rocheleau, D. W. Piston, and R. H. Goodman*. Metabolic regulation of SIRT1 transcription via a HIC1:CtBP co-repressor complex. Proc. Natl. Acad. Sci. U S A. 2007. 104:829-33 *corresponding author