John Denu

John Denu is a Professor at the University of Wisconsin–Madison leading the Denu Laboratory, which is part of the Microbiome, Epigenetics, and Multi-omics hubs at the Wisconsin Institute for Discovery. His research program investigates the molecular connections between metabolism and epigenetic pathways in human health and age-associated diseases. The lab employs biochemical, genetic, and multi-omics approaches to study chromatin dynamics, utilizing mammalian tissue culture systems and mouse models.

Denu's research interests center on understanding how metabolic pathways influence epigenetic regulation. His work focuses on three primary areas: the molecular links between metabolism and epigenetic pathways; the biochemical principles governing epigenetic information written onto histones; and the role of sirtuins in reversible protein acetylation. His lab explores how chromatin remodeling enzymes rely on metabolite-derived co-enzymes, suggesting coordination between nuclear events and metabolic networks. He investigates the hypothesis that chromatin modifying complexes have evolved to sense metabolite levels and respond accordingly.

Analysis of his recent publications reveals a strong focus on metabolism-epigenome interactions, with particular emphasis on sirtuins, histone modifications, and the role of specific metabolites like citrate and short-chain fatty acids in regulating chromatin function. His work spans from fundamental biochemical mechanisms to disease-relevant models, particularly in neurodegeneration and aging.

Denu mentors several graduate students including Jessica Han (who recently defended her PhD on diet, gut microbiome, and metabolism converging to remodel epigenetics) and Kellen Biesbrock (who joined in 2025). His lab actively collaborates with researchers across campus, including with Prof. Federico E. Rey in the Department of Bacteriology.

The Denu Laboratory employs an interdisciplinary approach spanning basic biochemistry to big data, using methods ranging from in vitro enzyme assays to high-throughput mass spectrometry. The lab is actively involved in many collaborations both on and off campus, reflecting the integrative nature of metabolism-epigenome research.