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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 post-translationally modify proteins, nicotinamide adenine dinucleotide (NAD)-consuming reactions control many biological processes and also display unique chemistry. Lin’s research focuses on NAD-consuming reactions in eukaryotic cells. His lab combines organic chemistry, biochemistry, cell biology, and animal models to understand how protein modifications, especially NAD-dependent modifications, regulate various biological pathways and contribute to human diseases.

Lin’s lab is currently studying sirtuins, a family of enzymes with NAD-dependent deacylase activity, that are important for aging, transcriptional regulation, and metabolism. His lab discovered that mammalian Sirt5 is a NAD-dependent desuccinylase and demalonylase and several sirtuins are defatty-acylases. These studies also helped to establish protein lysine succinylation and fatty acylation as common protein modifications that regulate various biological pathways. These discoveries in turn enable his lab to design potent and selective inhibitors for specific sirtuins. Some of these inhibitors have demonstrated interesting and broad anticancer activities. Lin also studies poly(ADP ribose) polymerases, or PARPs, that catalyze protein ADP-ribosylation, focusing on how PARPs regulate transcription in various cell signaling events.

Lin is a faculty member in the Tri-Institutional Ph.D. Program in Chemical Biology based at Weill Cornell Medicine [profile].