Michael Sack, M.D., Ph.D.

The Role of Caloric-Dependent Post-Translational Modifications in the Control of Metabolic and Mitochondrial Homeostasis:

I have had a long-standing interest in the mechanisms regulating mitochondrial biology and metabolism and the role in the pathophysiology of disease. At the basic science and translational level this work focusses on the role of the mitochondrial deacetylase enzyme SIRT3 and a counter-regulatory protein, GCN5L1 which modulates mitochondrial and cytosolic protein acetylation. Both of these proteins play pivotal roles in organelle responses to caloric-restriction and fasting and the role of these proteins are explored under fasting or fasting-mimetic conditions to delineate and characterize their functions. In parallel, an enlarging focus of my laboratory is translating what we have learnt in the laboratory into human biology and disease. Here, we use fasting and fasting mimetics as models to explore immunometabolism and immunomodulation in both healthy individuals and in inflammatory/autoimmune disease states. RNA-seq, proteomic and metabolomics data are being interrogated to identify novel pathways in innate and adaptive immune cells and then molecular and biochemical techniques are employed to characterize the function of these pathways and to assess if the manipulation of these pathways can modulate inflammatory or autoimmune disease.

Michael Sack graduated with his M.B.B.Ch. and M.Sc. from the University of Witwatersrand and earned his Ph.D. in 2000 from the University of Cape Town in South Africa. He did his internship at Johannesburg General Hospital and his internal medicine residency at Georgetown University Medical Center. He conducted cardiology research and did a clinical fellowship at Washington University Medical Center from 1994 to 1997. Dr. Sack joined the NHLBI in 2003. Dr. Sack has authored or coauthored more than 100 papers, editorials, reviews, and book chapters. He currently sits on the editorial boards of the Journal of Molecular and Cellular Cardiology, Mitochondrion, Journal of Gerontology, and Drug Discovery Today and is a member of the American Society for Clinical Investigation.