Department of Dermatology
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:
Q., D. W. Piston, and R. H. Goodman. Regulation of corepressor
function by nuclear NADH. Science. 2002 295:1895-7.
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
Q. *, S. Y. Wang, A. C. Nottke, J. V. Rocheleau, D. W. Piston,
and R. H. Goodman*. Redox sensor CtBP mediates hypoxia-induced tumor cell
migration. Proc. Natl. Acad. Sci. U S A. 2006 103:9029-33. *corresponding
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
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
Deng, Y., J. Liu, G. Han, S. L. Lu, S. Y. Wang, S. Malkoski,
A. C. Tan, C. Deng, X. J. Wang, and Q. Zhang. Redox-dependent Brca1 transcription
by an NADH-sensor CtBP1. Oncogene 2010 Dec 16;29(50):6603-8. PMID:
Deng, H., J. Liu, Y. Deng, G. Han, S. Shellman, Y. G.,
Robinson, S., Tentler, J., Robinson, W., Norris, D. A., X. J. Wang, and Q.
Zhang. CtBP1 is expressed in melanoma and represses
the transcription of p16INK4a
and Brca1. Journal of Investigative Dermatology 2013
Jan 10. PMID:23303449
Han, G., L. Bian, F. Li, A. Cotrim, D. Wang, J. B. Lu, Y.
Deng, G. Bird, A. Sowers, J. Mitchell, J. S. Gutkind, R. Zhao, D. Raben, P. ten
Dijke, Y. Refaeli, Q. Zhang* and X. J. Wang*. Preventive and therapeutic
effects of Smad7 on radiation-induced oral mucositis. Nature
Medicine 2013 Mar 10. doi: 10.1038/nm.3118. PMID: 23475202 *corresponding