Abstract

The Regulation of Mitochondrial Homeostasis and Metabolism in immunity is defined as immunometabolism. We are using fasting or fasting mimetics in human control subjects and in inflammatory disease to explore the mechanisms involved in fasting mediated control of inflammation. The immune cells we are focusing on include monocytes and CD4+ t cells. We are employing a systems biological approach using metabolomics, proteomics and RNA-seq with bioinformatic analysis to identify caloric-load effects. This will uncover novel regulatory pathways to explore under normal conditions and potentially provide pathways that can then be manipulated to assess in inflammatory disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL005102-15
Application #
10003764
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
2019
Total Cost
Indirect Cost

  Institution

Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Sack, Michael N (2018) Mitochondrial fidelity and metabolic agility control immune cell fate and function. J Clin Invest 128:3651-3661
Thapa, Dharendra; Wu, Kaiyuan; Stoner, Michael W et al. (2018) The protein acetylase GCN5L1 modulates hepatic fatty acid oxidation activity via acetylation of the mitochondrial ?-oxidation enzyme HADHA. J Biol Chem 293:17676-17684
Traba, Javier; Sack, Michael N (2017) The role of caloric load and mitochondrial homeostasis in the regulation of the NLRP3 inflammasome. Cell Mol Life Sci 74:1777-1791
Sack, Michael N; Fyhrquist, Frej Y; Saijonmaa, Outi J et al. (2017) Basic Biology of Oxidative Stress and the Cardiovascular System: Part 1 of a 3-Part Series. J Am Coll Cardiol 70:196-211
Traba, Javier; Geiger, Sarah S; Kwarteng-Siaw, Miriam et al. (2017) Prolonged fasting suppresses mitochondrial NLRP3 inflammasome assembly and activation via SIRT3-mediated activation of superoxide dismutase 2. J Biol Chem 292:12153-12164
Riley, Christopher L; Dao, Christine; Kenaston, M Alexander et al. (2016) The complementary and divergent roles of uncoupling proteins 1 and 3 in thermoregulation. J Physiol 594:7455-7464
Murphy, Elizabeth; Ardehali, Hossein; Balaban, Robert S et al. (2016) Mitochondrial Function, Biology, and Role in Disease: A Scientific Statement From the American Heart Association. Circ Res 118:1960-91
Traba, Javier; Kwarteng-Siaw, Miriam; Okoli, Tracy C et al. (2015) Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects. J Clin Invest 125:4592-600
Boylston, Jennifer A; Sun, Junhui; Chen, Yong et al. (2015) Characterization of the cardiac succinylome and its role in ischemia-reperfusion injury. J Mol Cell Cardiol 88:73-81
Alrob, Osama Abo; Sankaralingam, Sowndramalingam; Ma, Cary et al. (2014) Obesity-induced lysine acetylation increases cardiac fatty acid oxidation and impairs insulin signalling. Cardiovasc Res 103:485-97

Showing the most recent 10 out of 36 publications