One of the most fundamental questions in biology is how we age. The past decades have witnessed a significant revision of a traditional view that aging is simply a random and passive process that is solely driven by entropy. In fact, the aging process is regulated genetically and lifespan can be extended by single gene mutations. Our research aims to understand molecular and cellular mechanisms that regulate the aging process and explore therapeutic targets to slow aging and even reverse aging-associated degeneration. The most intriguing aspect of pharmaceutical intervention that targets the aging pathways is that, instead of targeting a specific disease, it has the potential of ameliorating a wide array of seemingly unrelated diseases associated with aging, such as cancer, tissue degeneration, metabolic syndrome, and immune dysfunction.
Ph.D. Molecular and Cell Biology, University of California at Berkeley
Xi, Y. and Chen, D. (2014). Partitioning the Circadian Clock. Science. 345(6201): 1122-3.
Shin, J.*, He, M.*, Liu, Y.*, Paredes, S.*, Villanova, L., Brown, K., Qiu, X., Nabavi, N., Mohrin, M., Wojnoonski, K., Li, P., Cheng, H., Murphy, A., Valenzuela, D., Luo, H., Kapahi, P., Krauss, R., Mostoslavsky, R., Yancopoulos, G., Alt, F., Chua, K., and Chen, D. (2013) SIRT7 Represses Myc Activity to Suppress ER Stress and Prevent Fatty Liver Disease. Cell Reports 5(3):654-665.
Brown, K.*, Xie, S.*, Qiu, X., Mohrin, M., Shin, J., Liu, Y., Zhang, D., Scadden, D., Chen, D. (2013) SIRT3 reverses aging-associated degeneration. Cell Reports 3(2):319-27.
Shin, J., Zhang, D., and Chen, D. (2011) Reversible acetylation of metabolic enzymes celebration: SIRT2 and p300 join the party. Molecular Cell. 43(1):3-5.
Qiu, X*., Brown, K*. (* equal contribution), Hirschey, M., Verdin, E., and Chen, D. (2010) Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metabolism. 12: 662-667.
Nakahata, Y., Kaluzova, M., Grimaldi, B., Sahar, S., Hirayama, J., Chen, D., Brunet, A., Guarente., L, and Sassone-Corsi, P. (2008) The NAD-dependent Deacetylase SIRT1 Modulates CLOCK-Mediated Chromatin Remodeling and Circadian Control. Cell. 134(2): 329-40.
Liu, Y.*, Dentin, R*., Chen, D.* (* equal contribution), Ravnskjaer, K., Cole, P., Olefsky, J., Yates, J., Guarente, L. and Montminy, M. (2008) SIRT1-modulated gluconeogenesis via deacetylation of TORC2. Nature. 456(7219): 269-73.
Chen, D., Bruno, J., Easlon, E., Lin, SJ., Alt, F. and Guarente, L. (2008) Tissue-specific regulation of SIRT1 by calorie restriction. Genes & Dev. 22(13): 1753-57.
Chen, D., and Guarente, L. (2007) Sir2: A potential target for calorie restriction mimetics. Trends in Molecular Medicine. 13(2): 64-71.
Chen, D., Steele, A., Lindquist, S., and Guarente, L. (2005) Increase in activity during calorie restriction requires Sirt1. Science. 310:1641. PMID: 16339438
Chen, D., and Zhou, Q. (2004) Caspase-cleavage of BimEL triggers a positive feedback amplification of apoptotic signaling. Proc. Natl. Acad. Sci. USA. 101(5): 1235-40. PMID: 14732682
Chen, D., Wang, M., Zhou, S., and Zhou, Q. (2002) HIV-1 Tat targets microtubules to induce apoptosis, a process promoted by the pro-apoptotic Bcl-2 relative Bim. EMBO J. 21(24):6801-10. PMID: 12486001
Chen, D., and Zhou, Q. (1999) Tat activates HIV-1 transcriptional elongation independent of TFIIH kinase. Mol. Cell. Bio. 19, 2863-2871. PMID: 10082552
Chen, D., Fong, Y., and Zhou, Q. (1999) Specific interaction of Tat with the human but not rodent P-TEFb complex mediates the species-specific Tat activation of HIV-1 transcription. Proc. Natl. Acad. Sci. USA. 96, 2728-2733. PMID: 10077579