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Department of Chemistry and Chemical Biology

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Faculty Detail

Lin, Hening


phone: 607/255-4650


Department Appointments

  • Department of Chemistry and Chemical Biology

Graduate Fields

  • Biochemistry, Molecular and Cell Biology
  • Chemistry and Chemical Biology
  • Microbiology
  • Pharmacology
  • Tri-Institutional Training Program in Chemical Biology (TPCB)


Protein posttranslational modifications, ADP-ribosylation, dipthamide, C-mannosylation


The Lin Group, an HHMI chemical biology lab at Cornell,  studies the chemistry, biology, and application of enzymes that have important physiological functions with a combination of synthetic and biochemical methods.


  • The chemistry, biology, and application of enzymes
  • Enzymes of particular interest are sirtuins, HDACs, PARPs, radical SAM enzymes, and CD38. Most of these enzymes are involved in protein post-translational modifications and have important biological functions.
  • We combine organic synthesis, biochemistry, biophysics, molecular biology, and cell biology to study the enzymology, identify the modified proteins, and study how the modification affects protein structure/function and thus the biological significance of the modification. We also develop small molecule inhibitors to target these enzymes and investigate their potentials in treating human diseases, such as cancer.

Selected Publications

  1. Jing H, and Lin H. “Sirtuins in Epigenetic Regulation”, Chem. Rev., 115, 2350-2375, 2015
  2. Liu X, Sadhukhan S, Sun S, Wagner GR, Hirschey MD, Qi L, Lin H, Locasale JW, “High resolution metabolomics with acyl-CoA profiling reveals widespread remodeling in response to diet.” Mol. Cell. Proteomics 2015, mcp.M114.044859
  3. Teng YB, Jing H, Aramsangtienchai P, He B, Khan S, Hu J, Lin H, Hao Q, “Efficient demyristoylase activity of SIRT2 revealed by kinetic and structural studies.” Sci. Rep. 5, 8529, 2015. doi: 10.1038/srep08529.
  4. Otwell AE, Sherwood RW, Zhang S, Nelson OD, Li Z, Lin H, Callister SJ, Richardson RE, “Identification of proteins capable of metal reduction from the proteome of the Gram-positive bacterium Desulfotomaculum reducens MI-1 using an NADH-based activity assay.” Environ. Microbiol. 2014, doi: 10.1111/1462-2920.12673. [Epub ahead of print]
  5. He B, Hu J,   Zhang X, and Lin H. “Thiomyristoyl peptides as cell-permeable Sirt6 inhibitors”, Org. Biomol. Chem., 12, 7498-7502, 2014
  6. Lin Z, Su X, Chen W, Ci B, Zhang S, Lin H. Dph7 catalyzes a previously unknown demethylation step in diphthamide biosynthesis. J Am Chem Soc. 2014 Link
  7. Shrimp JH, Hu J, Dong M, Wang BS, Macdonald RJ, Jiang H, Hao Q, Yen A, Lin H. Revealing CD38 Cellular Localization Using a Cell Permeable, Mechanism-Based Fluorescent Small Molecule Probe. J Am Chem Soc. 2014Link
  8. Dong M, Su X, Dzikovski B, Dando EE, Zhu X, Du J, Freed JH, Lin H. Dph3 is an electron donor for dph1-dph2 in the first step of eukaryotic diphthamide biosynthesis. J Am Chem Soc. 136, 1754-7, 2014 Link
  9. G. Colak, Z. Xie, A. Zhu, L. Dai, Z. Lu, Y. Zhang, X. Wan, Y. Chen, Y.H. Cha, H. Lin, Y. Zhao, and M. Tan, “Identification of Lysine Succinylation Substrates and the Succinylation Regulatory Enzyme CobB in Escherichia coli”. Mol. Cell. Proteomics, 12, 3509-3520, 2013
  10. Yu J, Sadhukhan S, Noriega LG, Moullan N, He B, Weiss RS, Lin H, Schoonjans K, Auwerx J. “Metabolic Characterization of a Sirt5 deficient mouse model”, Sci. Rep. 3, 2806, 2013.
  11. Su X, Lin Z, Lin H. The biosynthesis and biological function of diphthamide. Crit Rev Biochem Mol Biol. 2013 Link
  12. Hu J, He B, Bhargava S, Lin H. A fluorogenic assay for screening Sirt6 modulators. Org Biomol Chem. 11, 5213-6, 2013 Link
  13. Jiang H, Khan S, Wang Y, Charron G, He B, Sebastian C, Du J, Kim R, Ge E, Mostoslavsky R, Hang HC, Hao Q, Lin H. SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine. Nature. 496, 110-3. 2013 Link
  14. Jiang H, Lin H. Labeling Substrate Proteins of Poly(ADP-ribose) Polymerases with Clickable NAD Analog. Curr Protoc Chem Biol. 4, 19-34, 2012 Link
  15. Su X, Lin Z, Chen W, Jiang H, Zhang S, Lin H. Chemogenomic approach identified yeast YLR143W as diphthamide synthetase. Proc Natl Acad Sci U S A. 109, 19983-7, 2012 Link
  16. Jiang H, Sherwood R, Zhang S, Zhu X, Liu Q, Graeff R, Kriksunov IA, Lee HC, Hao Q, Lin H. Identification of ADP-ribosylation sites of CD38 mutants by precursor ion scanning mass spectrometry. Anal Biochem. 433, 218-26. 2012 Link
  17. Zhou Y, Zhang H, He B, Du J, Lin H, Cerione RA, Hao Q. The bicyclic intermediate structure provides insights into the desuccinylation mechanism of human sirtuin 5 (SIRT5). J Biol Chem. 287, 28307-14, 2012 Link
  18. Lin H, Su X, He B. Protein lysine acylation and cysteine succination by intermediates of energy metabolism, ACS Chem Biol. 7, 947-60, 2012 Link
  19. He B, Du J, Lin H. Thiosuccinyl peptides as Sirt5-specific inhibitors, J Am Chem Soc, 134, 1922-5, 2012 Link
  20. Su X, Chen W, Lee W, Jiang H, Zhang S, Lin H. YBR246W is required for the third step of diphthamide biosynthesis, J Am Chem Soc, 134(2), 773-6, 2012 Link
  21. Zhu AY, Zhou Y, Khan S, Deitsch KW, Hao Q, Lin H. Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine, ACS Chem Biol. 7, 155-9, 2012 Link
  22. J. Du, Y. Zhou, X. Su, J. Yu, S. Khan, H. Jiang, J. Kim, J. Woo, J. Kim, B. Choi, B. He, W. Chen, S. Zhang, R. Cerione, J. Auwerx, Q. Hao, and H.Lin. Sirt5 is a NAD-Dependent Protein Lysine Demalonylase and Desuccinylase, Science. Vol. 334, No 6507, 806-809, 2011 Link
  23. H. Lin, “S-Adenosylmethionine-dependent alkylation reactions: When are radical reactions used?” Bioorg. Chem. 39, 161-170 (2011).
  24. X. Zhu, B. Dzikovski, X. Su, A.T. Torelli, Y. Zhang, S.E. Ealick, J.H. Freed, and H. Lin. Mechanistic understanding of Pyrococcus horikoshii Dph2, a [4Fe-4S] enzyme required for diphthamide biosynthesis, Mol. BioSystems. 7, 74-81, 2011 Link
  25. J. Congleton, H. Jiang, F. Malavasi, H. Lin, A. Yen, “ATRA-induced HL-60 myeloid leukemia cell differentiation depends on the CD38 cytosolic tail needed for membrane localization, but CD38 enzymatic activity is unnecessary” Exp. Cell Res. 317, 910-919 (2011).
  26. X. Zhu, J. Kim, X. Su, and H. Lin. Reconstitution of diphthine synthase activity in vitro, Biochemistry. 49, 9649-9657, 2010 . Link
  27. Hong Jiang, Jun Hyun Kim, Kristine M. Frizzell, W. Lee Kraus and Hening Lin;Clickable NAD Analogues for Labeling Substrate Proteins of Poly(ADP-ribose) Polymerases, JACS. (2010) Link
  28. Yang Zhang, Xuling Zhu, Andrew T. Torelli, Michael Lee, Boris Dzikovski, Rachel M. Koralewski, Eileen Wang, Jack Freed, Carsten Krebs, Steven E. Ealick & Hening Lin;Diphthamide biosynthesis requires an organic radical generated by an iron–sulphur enzyme, Nature. 465,891-896 (2010) Link
  29. Q. Liu, R. Graeff, I. A. Kriksunov, H. Jiang, B. Zhang, B. V. L. Potter, N. Oppenheimer, H. Lin, H. C. Lee, Q. Hao, “Structural Basis for Enzymatic Evolution from a Dedicated ADP-ribosyl Cyclase to a Multi- functional NAD Hydrolase”, J. Biol. Chem., 284, 27637-27645, (2009). Link
  30. H. Jiang, J. Congleton, Q. Liu, P. Merchant, F. Malavasi, H.C. Lee, Q. Hao, A. Yen, H. Lin, “Mechanism-Based Small Molecule Probes for Labeling CD38 on Live Cells”, J. Am. Chem. Soc., 131, 1658-1659 (2009) Link Highlighted in Nat. Chem. Biol. 5, 149 (2009) link
  31. J. Du, H. Jiang, H. Lin, “Investigating the ADP-ribosyltransferase activity of sirtuins with NAD analogs and 32P-NAD”, Biochemistry 48, 2878–2890 (2009) Link
  32. Q. Liu, I.A. Kriksunov, H. Jiang, R. Graeff, H. Lin, H.C. Lee, Q. Hao,“Covalent and non-covalent intermediates of an NAD utilizing enzyme – human CD38”, Chem. Biol. 15,1068-78 (2008) Link
  33. H. Lin, J. Du, H. Jiang, “Posttranslational modifications to regulate protein function”, Wiley Encyclopedia of Chemical Biology, 2008. John Wiley & Sons, Inc. DOI: 10.1002/9780470048672. wecb467 Link
  34. H. Lin, “Nicotinamide adenine dinucleotide: beyond a redox coenzyme”, Org. Biomol. Chem., 5, 2541-2554 (2007) Link