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

Senior Investigator

Laboratory of Mitochondrial Biology and Metabolism


Building 10, Room 5-3150
10 Center Drive
Bethesda, MD 20814



Research Topics

Dr. Sack’s laboratory focuses on modifications of proteins that play pivotal roles in metabolism and mitochondrial function to understand how these modifications affect disease risk. The major regulatory proteins being explored in the Sack laboratory include SIRT3, GCN5L1 and Parkin. The effects of these nutrient- and stress-regulatory proteins on mitochondrial biology and metabolism are explored in the context of disease pathophysiology with studies in both experimental systems with translation to the human subjects. The objective of these studies are to understand how nutrient- and other stress- signaling events cause or exacerbate disease and whether therapeutic interventions can be tested that reverse these pathologies. Current diseases being explored include cardiovascular disease, immune activation and Early Onset Parkinson 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.

Selected Publications

  1. Traba J, Kwarteng-Siaw M, Okoli TC, Li J, Huffstutler RD, Bray A, Waclawiw MA, Han K, Pelletier M, Sauve AA, Siegel RM, Sack MN. Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects. J Clin Invest. 2015;125(12):4592-600.
  2. Wang L, Scott I, Zhu L, Wu K, Han K, Chen Y, Gucek M, Sack MN. GCN5L1 modulates cross-talk between mitochondria and cell signaling to regulate FoxO1 stability and gluconeogenesis. Nat Commun. 2017;8(1):523.
  3. Wu K, Seylani A, Wu J, Wu X, Bleck CKE, Sack MN. BLOC1S1/GCN5L1/BORCS1 is a critical mediator for the initiation of autolysosomal tubulation. Autophagy. 2021;17(11):3707-3724.
  4. Wu J, Singh K, Lin A, Meadows AM, Wu K, Shing V, Bley M, Hassanzadeh S, Huffstutler RD, Schmidt MS, Blanco LP, Tian R, Brenner C, Pirooznia M, Kaplan MJ, Sack MN. Boosting NAD+ blunts TLR4-induced type I IFN in control and systemic lupus erythematosus monocytes. J Clin Invest. 2022;132(5).
  5. Han K, Singh K, Rodman MJ, Hassanzadeh S, Wu K, Nguyen A, Huffstutler RD, Seifuddin F, Dagur PK, Saxena A, McCoy JP, Chen J, Biancotto A, Stagliano KER, Teague HL, Mehta NN, Pirooznia M, Sack MN. Fasting-induced FOXO4 blunts human CD4+ T helper cell responsiveness. Nat Metab. 2021;3(3):318-326.

Related Scientific Focus Areas

This page was last updated on Wednesday, August 24, 2022