Dr. Wolfgang's laboratory studies the role and regulation of cellular and organismal metabolism. The research in the Wolfgang laboratory utilizes biochemistry and molecular genetics to understand the molecular mechanisms used to sense and respond to nutritional/metabolic cues. They are particularly interested in deciphering the roles of unexplored metabolic enzymes/pathways and determining novel roles of cannonical metabolic pathways in under-explored cells and tissues.
Dr. Wolfgang’s lab is interested in the regulation of energy homeostasis by the central nervous system, specifically its interaction with the organs and tissues—muscle, liver, fat—that control energy use and expenditure. This interaction often is disrupted in obese and diabetic patients and leads to an inability to regulate body weight and blood sugar within normal ranges. Obesity and diabetes have become serious problems in Western medical science, and are a growing problem throughout the world. Understanding the molecular mechanisms underpinning these conditions is critical to formulating new interventions. To this end, we use biochemical and molecular genetic techniques to better understand how the brain controls energy use.
Some of the most interesting, enigmatic and understudied cells in metabolic biochemistry are those of the nervous system. Defects in neural cell pathways can lead to devastating neurological disease. Conversely, altering the metabolic properties of the nervous system can have surprisingly beneficial effects on the progression of some diseases.
Dr. Wolfgang’s lab uses biochemical and molecular genetic techniques to understand the molecular mechanisms that the nervous system uses to sense and respond to metabolic cues. His lab has uncovered novel neuronal nutrient-sensing paradigms that act through unique metabolic enzymes to control body weight and diabetes susceptibility. The lab continues to explore novel neuron-specific enzyme function in metabolic processes and novel roles of canonical metabolic pathways in the nervous system. Furthermore, the unique makeup of the nervous system requires the laboratory to develop new technology and assays to facilitate their work.
Bowman CE, Selen Alpergin ES, Cavagnini K, Smith DM, Scafidi S, Wolfgang MJ. "Maternal lipid metabolism directs fetal liver programming following nutrient stress." Cell Reports 2019; 29:1299-1310
Lee J, Choi J, Selen Alpergin ES, Zhao L, Hartung T, Scafidi S, Riddle RC, Wolfgang MJ. "Loss of hepatic mitochondrial long chain fatty acid oxidation confers resistance to diet-induced obesity and glucose intolerance." Cell Reports 2017; 20:655-667
Bowman CE, Rodriguez S,Selen-Alpergin E, Acoba MG, Zhao L, Hartung T, Claypool SM, Watkins PA, Wolfgang MJ. "The mammalian malonyl-CoA synthetase ACSF3 is required for mitochondrial protein malonylation and metabolic efficiency." Cell Chemical Biology 2017; 24:673-684
Lee J, Choi J, Scafidi S, Wolfgang MJ. "Hepatic fatty acid oxidation restrains systemic catabolism during starvation." Cell Reports 2016: 16: 201-212.
Bowman CE, Zhao L, Hartung T, Wolfgang MJ. "Requirement for the mitochondrial pyruvate carrier in mammalian development revealed by a hypomorphic allelic series." Mol Cell Biol 2016; 36(15):2089-2104.
Lee J, Choi J, Aja S, Scafidi S, Wolfgang MJ. "Loss of adipose fatty acid oxidation does not potentiate obesity at thermoneutrality." Cell Reports 2016; 14:1308-1316.
Nomura M, Liu J, Rovira IL, Gonzalez-Hurtado E, Lee J, Wolfgang MJ*, Finkel T.* "The role of fatty acid oxidation in macrophage polarization." Nature Immunology 2016; 17(3): 216-217. (*Co-corresponding authors)
Lee J, Ellis JM, Wolfgang MJ. "Adipose fatty acid oxidation is required for thermogenesis and potentiates oxidative stress induced inflammation." Cell Reports 2015; 10(2): 266-279.
Ellis JM, Wong GW, Wolfgang MJ. "Acyl Coenzyme A Thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity." Mol Cell Biol. 2013; 33(9) 1869-1882.