Focus: Chemical Biology
- Ph.D., Organic Chemistry, Michigan State University, East Lansing, MI
- M.S., Organic Chemistry, Beijing Normal University, Beijing, China
- B.S., Chemistry, Beijing Normal University, Beijing, China
COURSES TAUGHT AT ACPHS
- Our research program focuses on the design and synthesis of molecular probes and therapeutic agents targeting epigenetic modifying enzymes. The ultimate goal is to translate these findings into novel treatments for cancers and age-related diseases.
- Sirtuins (or Class III HDACs) are involved in central physiological regulation mechanisms, many of them with relevance to metabolic regulation and aging processes. Therefore, the seven mammalian sirtuin isoforms are emerging targets for the treatment of metabolic disorders and aging-related diseases. Despite the intense pursuit of sirtuin-targeted therapeutics, the connection between sirtuins and disease pathogenesis is not fully understood. To elucidate the transient but essential functions of sirtuins, traditional biological and genetic tools are often limited due to the lethal or slow responses of these enzymes at gene level. The need for novel chemical tools to evaluate sirtuin activity in native biological system is apparent. We will take advantage of the unique sirtuin catalytic mechanism: 1) to engineer active-site directed chemical probes for profiling sirtuins in native proteomes and live cells; 2) to design and identify potent, isoform-specific small-molecule sirtuin regulators as pharmacological modulators and anti-cancer reagents.
- The New York Academy of Science (2010-present)
- Sigma Xi, the Scientific Research Society (2009-present)
- American Association for the Advancement of Science (2007-present)
- American Chemical Society (2001-present)
Kraus, D.; Yang, Q.; Kong, D.; Banks, A. S.; Zhang, L.; Rodgers, J. T.; Pirinen, E.; Pulinilkunnil, T. C.; Gong, F.; Wang, Y. C.; Cen, Y.; Sauve, A. A.; Asara, J. M.; Peroni, O. D.; Monia, B. P.; Bhanot, S.; Alhonen, L.; Puigserver, P.; Kahn, B. B., “Nicotinamide N-methyltransferase Knockdown Protects against Diet-induced Obesity”, Nature, 2014, 508, 258-262.
Laurent, G.; de Boer, V. V.; Finley, L. W.; Sweeney, M.; Lu, H.; Schug, T. T.; Cen, Y.; Jeong, S. M.; Sauve, A. A.; Haigis, M. C., “SIRT4 Represses Peroxisome Proliferator-activated Receptor Activity to Suppress Hepatic Fat Oxidation”, Molecular and Cellular Biology, 2013, 33, 4552-4561.
Cantó, C.; Houtkooper, R. H.; Pirinen, E.; Youn, D. Y.; Oosterveer, M. H.; Cen, Y.; Fernandez-Marcos, P. J.; Yamamoto, H.; Andreux, P. A.; Cettour-Rose, P.; Gademann, K.; Rinsch, C.; Schoonjans, K.; Sauve, A. A.; Auwerx, J., “The NAD+ Precursor Nicotinamide Riboside Enhances Oxidative Metabolism and Protects against High-Fat Diet-Induced Obesity ”, Cell Metabolism, 2012, 15, 838-847.
Cen, Y.; Youn, D. Y.; Sauve, A. A., “Advances in Characterization of Human Sirtuin Isoforms: Chemistries, Targets and Therapeutic Applications”, Current Medicinal Chemistry, 2011, 18, 1919-1935.
Bai, P.; Canto, C.; Oudart, H.; Brunyánszki, A.; Cen, Y.; Thomas, C.; Yamamoto, H.; Huber, A.; Kiss, B.; Houtkooper, R. H.; Schoonjans, K.; Schreiber, V.; Sauve, A. A.; Meinissier-de Murcia. J.; Auwerx, J., “PARP-1 Inhibition Increases Mitochondrial Metabolism through SIRT1 Activation”, Cell metabolism, 2011, 13, 461-468.
Bai, P.; Canto, C.; Brunyánszki, A.; Huber, A.; Szántó, M.; Cen, Y.; Yamamoto, H.; Houten, S. M.; Kiss, B.; Oudart, H.; Gergely, P.; Meinissier-de Murcia. J.; Schreiber, V.; Sauve, A. A.; Auwerx, J., “PARP-2 Regulates SIRT1 Expression and Whole-Body Energy Expenditure”, Cell metabolism, 2011, 13, 450-460.
Cen, Y.; Falco, J. N.; Xu, P.; Youn, D. Y.; Sauve, A. A., “Mechanism-based Affinity Capture of Sirtuins”, Organic & Biomolecular Chemistry, 2011, 9, 987-993.
French, J. B.; Cen, Y.; Vrablik, T. L.; Xu, P.; Allen, E.; Hanna-Rose, W.; Sauve, A. A., “Characterization of Nicotinamidases: Steady State Kinetic Parameters, Classwide Inhibition by Nicotinaldehydes, and Catalytic mechanism”, Biochemistry, 2010, 49, 10421-10439.
French, J. B.; Cen, Y.; Sauve, A. A.; Ealick, S. E., “High-Resolution Crystal Structures of Streptococcus pneumoniae Nicotinamidase with Trapped Intermediates Provide Insights into the Catalytic Mechanism and Inhibition by Aldehyde”, Biochemistry, 2010, 49, 8803-8812.
Cen, Y.; Sauve, A. A., “Transition State of ADP-ribosylation of Acetyllysine Catalyzed by Archeaoglobus fulgidus Sir2 Determined by Kinetic Isotope Effects and Computational Approaches”, Journal of the American Chemical Society, 2010, 132, 12286-12298.
Cen, Y., “Sirtuins Inhibitors: The Approach to Affinity and Selectivity”, Biochimica et Biophysica Acta (BBA)-Proteins & Proteomics, 2010, 1804, 1635-1644.
Cen, Y.; Sauve, A. A., “Diastereocontrolled Electrophilic Fluorination of 2’-Deoxyribonolactone: Syntheses of All Corresponding 2-Deoxy-2-fluoro-lactones and 2’-Deoxy-2’-fluoro-NAD+s”, Journal of Organic Chemistry, Featured Article, 2009, 74, 5779-5789.
French, J.; Cen, Y. (co-first author); Sauve, A. A., “Plasmodium falciparum Sir2 is an NAD+-dependent Deacetylase and an Acetyllysine-dependent and Acetyllysine-independent NAD+ Glycohydrolase”, Biochemistry, 2008, 47, 10227-10239.
Fulco, M.; Cen, Y.; Zhao, P.; Hoffman, E. P.; McBurney, M. W.; Sauve, A. A.; Sartorelli, V., “Glucose Restriction Inhibits Skeletal Myoblast Differentiation by Activating SirT1 through AMPK-Mediated Regulation of Nampt”, Developmental Cell, 2008, 14, 661-673.
Cen, Y., “Transition State of ADP-ribosylation of Acetyllysine Catalyzed by Plasmodium falciparum and Archeaoglobus fulgidus Sirtuins”, Keystone Symposium Sirtuins in Metabolism, Aging and Disease, Tahoe City, CA, February 2012
Cen, Y., “Transition State of ADP-ribosylation of Acetyllysine Catalyzed by Archeaoglobus fulgidus Sir2 Determined by Kinetic Isotope Effects and Computational Approaches”, NYAS Chemical Biology Discussion Group Year-End Meeting, New York, NY, June 2011
Cen, Y.; Sauve, A. A., “Mechanism for NAD+ Hydrolysis at pH 9 as Determined by Kinetic Isotope Effects and Computational Analysis”, The 40th American Chemical Society Middle Atlantic Regional Meeting, New York, NY, May 2008
Cen, Y.; Sauve, A. A., “A Switch of Mechanism for NAD+ Hydrolysis at Alkaline pH Featuring Pronounced Primary 14C and α-Secondary 3H Kinetic Isotope Effects”, Gordon Research Conference-Isotope in Biological and Chemical Science, Ventura, CA, February 2008
Cen, Y.; Wagner, P. J., “Photocyclization of 2-Alkoxy-3-alkyl Phenyl Ketones”, 230th American Chemical Society National Meeting, Washington D. C., August 2005