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Michael Wolfgang Portrait

Michael Wolfgang
Associate Professor of Biological Chemistry
Johns Hopkins University School of Medicine

475 Rangos Building
855 N. Wolfe St.
Baltimore, MD21205
Office Phone: 443-287-7680
Lab Phone: 443-287-7214
Fax: 410-614-8033
Email: mwolfga1@jhmi.edu
Lab Web Site

Click Here for PDF of CV

Neurometabolic regulation of behavior and physiology in obesity, diabetes and neurological disease.

Our laboratory is interested in understanding the metabolic properties of neurons and glia at a mechanistic level in situ. Some of the most interesting, enigmatic and understudied cells in metabolic biochemistry are those of the nervous system. Defects in these 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. However, the mechanisms of these interactions are largely unknown.

We utilize biochemical and molecular genetic techniques to understand the molecular mechanisms that the nervous system uses to sense and respond to metabolic cues. We have uncovered novel neuronal nutrient sensing paradigms that act through unique metabolic enzymes to control body weight and diabetes susceptibility. We continue to explore novel neuron-specific enzyme function in metabolic processes as well as uncovering novel roles of canonical metabolic pathways in the nervous system. Furthermore, the unique makeup of the nervous system requires our laboratory to develop new technology and assays to facilitate our work.

Below are the broad areas that we are currently focusing on. 

  1. Deconstructing neurometabolic pathways. How does the nervous system utilize bioenergetic substrates and how does the disruption of these pathways affect animal behavior and physiology? Here we use tissue specific gain and loss of function mouse models to understand the biochemistry of the nervous system and how these metabolic pathways impact animal behavior and physiology. We are currently investigating several neuron-specific and canonical enzymes in fatty acid biochemistry.  
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  3. Metabolic heterogeneity. The nervous system represents a unique challenge for biochemists in part because of the great diversity of neurons and glia, and the abundant metabolite shuttling that occurs between cells. To understand metabolism in the nervous system, we must understand how these different cells contribute uniquely to metabolic processes. Here we are developing novel tools to measure and manipulate metabolic pathways in single cells in vivo.  
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  5. The evolution of metabolic adaptation. Nature has performed some of the most elegant experiments over an enormous time scale. Understanding how enzymes have changed over time or in species that are under different environmental stress can be invaluable to understanding ourselves. Here we try to ask many of the why questions in metabolism. Why has carbohydrate metabolism been selected for the brain over and over again in almost every species? What is the consequence of changing bioenergetics substrates?
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Recent Publications

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.
PubMed Reference

Ellis JM & Wolfgang MJ.  A genetically encoded metabolite sensor for malonyl-CoA.  Chemistry & Biology 2012 Oct 26; 19(10) 1333-1339.
PubMed Reference

Miyamoto T, DeRose R, Suarez A, Ueno T, Chen M, Sun T, Wolfgang MJ, Mukherjee C, Meyers DJ and Inoue T. Generation of Intracellular Logic Gates with Two Orthogonal Chemically Inducible Systems. Nature Chemical Biology 2012, Mar 25;8(5):465-70.
PubMed Reference

Rodriguez S & Wolfgang MJ. Targeted chemical-genetic regulation of protein stability in vivo. Chemistry & Biology 2012, Mar 23;19(3):391-8.
PubMed Reference

Reamy AA & Wolfgang MJ. Carnitine Palmitoyltransferase-1C gain-of-function in the brain results in postnatal microencephaly. Journal of Neurochemistry. 2011 Aug; 118(3) 388-98.
PubMed Reference

Cha SH, Wolfgang M, Tokutake Y, Chohnan S, Lane MD. Differential effects of central fructose and glucose on hypothalamic malonyl-CoA and food intake. Proc Natl Acad Sci USA. 2008;105(44):16871-5.
PubMed Reference

Wolfgang MJ, Cha SH, Millington DS, Cline G, Shulman GI, Suwa A, Asaumi M, Kurama T, Shimokawa, T & Lane MD. Brain-specific carnitine palmitoyltransferase-1c:  Role in CNS fatty acid metabolism, food intake and body weight. J Neurochem 2008; May;105(4):1550-9.
PubMed Reference

Wolfgang MJ, Cha SH, Sidhaye A, Chohnan S, Cline G, Shulman GI & Lane MD. Regulation of hypothalamic malonyl-CoA by central glucose and leptin. Proc Natl Acad Sci USA. 2007 Dec; 104(49): 19285-19290.
PubMed Reference

Chakravarthy MV, Zhu Y, López M, Yin L,  Wozniak DF, Coleman T, Hu Z, Wolfgang M, Vidal-Puig A,  Lane MD & Semenkovich CF. Brain fatty acid synthase activates PPARa to maintain energy homeostasis.  J Clin Invest. 2007; 117: 2539-2552.
PubMed Reference

Wolfgang MJ & Lane MD. The role of hypothalamic malonyl-CoA in energy homeostasis. J. Biol. Chem. 2006; 281(49): 37265-37269.
PubMed Reference

Wolfgang MJ, Kurama T, Dai Y, Suwa A, Asaumi M, Matsumoto S, Cha SH, Shimokawa T & Lane MDThe brain-specific carnitine palmitoyltransferase-1c regulates energy homeostasis. Proc. Natl. Acad. Sci. USA 2006 May; 103(19): 7282-7287.
PubMed Reference

Gao Q*, Wolfgang MJ*, Neschen S, Morino K, Horvath, TL, Shulman GI, & Fu XY.  Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility and thermal dysregulation.  Proc. Natl. Acad. Sci. USA 2004 March; 101(13): 4661-4666. (*equal contribution).
PubMed Reference

Kano A*, Wolfgang MJ*, Gao Q*, Jacoby J, Chai GX, Hansen W, Iwamoto Y, Pober JS, Flavell RA, & Fu XY.  Endothelial cells require STAT3 for protection against endotoxin-induced inflammation.  J Exp Med.  2003; 198(10): 1517-1525. (*equal contribution).
PubMed Reference


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