Research Interests
- Michael N. Sack, M.D., Ph.D. Research

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.

Selected Publications

Increased mitochondrial biogenesis and ROS production accompanying prolonged CD4+ T cell activation.

Authors: Akkaya B, Roesler AS, Miozzo P, Theall BP, Smelkinson M, Kabat J, Traba J, Sack MN, Brzostowski J, Al Souz J, Dorward DW, Pierce SK, Akkaya M.
J Immunol. 2018 Dec 01;201(11):3294-3306

A Pilot Study To Investigate the Immune-Modulatory Effects of Fasting in Steroid-Naive Mild Asthmatics

Authors: Han K, Nguyen A, Traba J, Yu X, Kayler M, Huffstutler RD, Levine SJ, Sack MN.
J Immunol. 2018 Sep 01;201(5):1382-1388

Second Signals Rescue B Cells From Activation-Induced Mitochondrial Dysfunction and Death

Authors: 5. Akkaya M, Traba J, Roesler AS, Miozzo P, Akkaya B, Theall BP, Sohn H, Pena M, Smelkinson M, Kabat J, Dahlstrom E, Dorward D, Sack MN, Pierce SK.
Nat Immunol. 2018 Aug 01;19(8):871-884