John Denu

Integrative Omics Core for Metabolism Research Denu Lab

My lab investigates the reciprocal link between metabolism and epigenetic states, revealing the mechanism and biological function of reversible protein modifications involved in modulating signal transduction, chromatin dynamics and metabolism. These studies have demonstrated that protein acetylation is a regulatory mechanism for controlling major metabolic pathways. The group has developed proteomic methods to query protein modifications on histone and non-histone proteins, discovering several novel mechanisms by which metabolism informs acetylation- and methylation-dependent pathways, with particular emphasis on the sub-cellular mechanisms of proteome-wide lysine acetylation and how various forms of metabolic stress (diet, obesity, diabetes) alter the methylation and acylation state of chromatin. This work involves integrating diverse approaches that cover mechanistic enzymology, quantitative proteomics, cellular biochemical pathways, mammalian model organisms, and human samples. Major projects include i) understanding how metabolism is linked to epigenome regulation ii) revealing the molecular role of NAD+-dependent deacylases in aging and metabolic disease iii) understanding how dysregulation of the epigenome affects age-associated diseases and iv) understanding how gut microbial metabolites affect host phenotypes.