Scientists & Research

Hening Lin, Ph.D.

Cells carry out numerous chemical reactions to achieve diverse biological functions. For example, phosphorylation of proteins is involved in many cell signaling processes, and histone acetylation and methylation provide epigenetic control. Of all the reactions that posttranslationally modify proteins, nicotinamide adenine dinucleotide (NAD)-consuming reactions stand out as they not only control many biological processes including transcription, aging, DNA repair, mitosis and telomere maintenance, but they also display very interesting chemistry. Dr. Lin’s research focuses on NAD-consuming reactions in eukaryotic cells. His laboratory combines organic synthesis, biochemistry and genetics to discover new reactions that consume NAD and new biological pathways that are regulated by known or new NAD-consuming reactions.

Dr. Lin is interested in what biological pathways are regulated by enzymes in the family that catalyze NAD-consuming reactions, as very few of those enzymes have been functionally characterized. For example, mammals have 17 poly (ADP ribose) polymerases that catalyze protein poly(ADP-ribosyl)ation, but the biological functions are only known for two of them, PARP-1 (required for DNA repair and transcription of certain genes) and Tankyrase-1 (promoting telomere extension and required for mitosis). Furthermore, the NAD-dependent deacetylation reactions were only discovered in 2000, and there is no sequence homology between different enzymes that catalyze different NAD-consuming reactions. Therefore it is very likely that new NAD-consuming reactions are still waiting to be discovered. Dr. Lin’s lab uses organic synthesis to make various NAD analogues that, combined with biochemistry and RNA interference, allow the tagging and identification of NAD-consuming enzymes and substrates, which in turn allows the discovery of new NAD-dependent reactions and biological pathways that are regulated by NAD-consuming reactions.

• Zhang, Y. et al. Diphthamide biosynthesis requires an organic radical generated by an iron–sulphur enzyme. Nature, 465, 891–896 (2010).
• Du, J. et al. Investigating the ADP-ribosyltransferase activity of sirtuins with NAD analogs and ³²P-NAD. Biochemistry 48, 2878–2890 (2009).
• Jiang, H. et al. Mechanism-based small molecule probes for labeling CD38 on live cells. J. Am. Chem. Soc. 131, 1658–1659 (2009).