Published: 13-02-2019 13:09 | Updated: 16-02-2024 15:18

Professor Mitchell Lazar receives the 2019 Rolf Luft Award

Professor Mitchell Lazar

Professor Mitchell Lazar at Perelman School of Medicine, University of Pennsylvania, Philadelphia has been selected as recipient of the Rolf Luft Award 2019.

The Prize Lecture “Nuclear Receptors, Circadian Rhythms, and Metabolism" was held by Professor Lazar at the Prize Ceremony, in Nobel Forum, on May 8th, 2019.

Prize motivation

Professor Mitchell Lazar is receiving the 2019 Rolf Luft Award for his pioneering work in transcriptional regulation of metabolism. Dr Lazar is professor of Medicine and Genetics at the University of Pennsylvania, Perelman School of Medicine in Philadelphia. His work encompass the discovery of resistin, elucidation of the role of PPARg in adipose biology and the links between obesity and insulin resistance, and demonstration of causal links between the molecular circadian clock and metabolism. He discovered the circadian nuclear receptor Rev-erbα and identified mechanisms by which it represses gene transcription as a core circadian clock component and a controller of metabolic rhythms. Dr Lazar uncovered the unique DNA sequence bound by Rev-erbα, its endogenous heme ligand, and the "CoRNR box" that mediates corepressor interaction with nuclear receptors. He discovered the nuclear receptor corepressor complex that activates the epigenome modifying enzyme histone deacetylase 3 and demonstrated that Rev-erbα recruits this complex to generate circadian rhythms of epigenome modification and metabolic gene expression in the liver. Dr Lazar demonstrated the chromatin looping mechanisms by which Rev-erbα functions as a core component of the clock that exists in all cells, yet cooperates with lineage specific factors to modulate metabolic physiology in a tissue-specific manner. The importance of circadian mechanisms in the pathophysiology of metabolic diseases associated with shift work is now widely recognized. Hence, the discoveries made by Dr Mitchell Lazar spans molecular biology, physiology, endocrinology and metabolism, and have translational relevance and considerable therapeutic potential.

Rolf Luft Award is awarded annually by Karolinska Institutet for outstanding scientific contribution in endocrinology and diabetes.

Contact

Professor Per-Olof Berggren, phone +46-(0)8-517 757 31, e-mail  

Per-Olof.Berggren@ki.se