Martin G Myers M.D., Ph.D.
| 5510 MSRB I |
| Ann Arbor, MI 48109 |
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The hormone leptin signals the body‚ nutritional and metabolic status to the brain to regulate glycemic control, energy balance, and neuroendocrine function. Leptin acts via the long form of its receptor (LRb) to regulate numerous distinct populations of neurons in the hypothalamus and elsewhere in the brain. Each different set of LRb-expressing neurons serves a different function, and the totality of leptin action requires the coordinated response of all LRb neurons. While my original background is in the molecular mechanisms of intracellular LRb signaling, our focus includes the study of the neural mediators of leptin action, since it is not possible to understand the regulation of metabolism and endocrine function without understanding the neurophysiologic as well as molecular basis of leptin action. Thus, in addition to examining the molecular details and importance of specific LRb signals, we are dissecting the regulation and function of individual populations of LRb-expressing neurons and examining the role of leptin in the development of neural circuits. By understanding the totality of leptin action in this way we hope to decipher the mechanisms by which leptin regulates the predisposition to diabetes and other aspects of the metabolic syndrome.
Feener E, Rosario F, Dunn SL, Stancheva Z and Myers MG Jr. Inhibition of Jak2 signaling by tyrosine phosphorylation in the JH2 domain. Mol Cell Biol (2004) 24(11): 4968-78.
Bates SH, Dundon TA, Seifert M, Maratos-Flier E and Myers MG Jr. LRb-STAT3 signaling is required for the neuroendocrine regulation of energy expenditure. Diabetes (2004) 53(12): 3067-3073.
Dunn SL, Bjornholm, M, Bates, SH, Seifert M, Chen Z, and Myers MG Jr. Feedback inhibition of leptin receptor/Jak2 signaling by Tyr1138 of the Leptin receptor and Suppressor of Cytokine Signaling 3. Mol Endo (2005) 19: 925-938.
Bates SH, Kulkarni RN, Seifert M, and Myers MG Jr. Roles for leptin receptor/STAT3-dependent and -independent signaling in the regulation of glucose homeostasis. Cell Metabolism (2005) 1: 169-178.
Gelling RW, Morton GJ, Morrison CD, Niswender KD, Myers MG Jr, Rhodes CJ, and Schwartz MW. Insulin action in the brain contributes to glucose lowering during insulin treatment of diabetes. Cell Metabolism (2006) 3: 67-73.
Ishida-Takahashi R, Rosario F, Gong Y, Kopp K, Stancheva Z, Chen X, Feener EP, and Myers MG Jr. Phosphorylation of Jak2 on Ser523 Inhibits Jak2-dependent Leptin Receptor Signaling. Mol Cell Biol (2006) 26: 4063-73.
Buettner C, Pocai A, Muse E, Etgen A, Myers MG Jr, and Rossetti L. Critical Role of STAT3 in Leptin‚ Metabolic Actions. Cell Metabolism (2006) 4:49-60.
Munzberg H, Jobst EE, Bates SH, Jones JC, Villanueva E, Leshan R, Bjornholm M, Elmquist J, Sleeman M, Cowley MA, and Myers MG Jr. Appropriate Inhibition of orexigenic hypothalamic arcuate nucleus neurons independently of leptin receptor/STAT3 signaling. J. Neurosci. (2007) 27: 69-74.
Bjornholm M, Munzberg H, Leshan R, Villanueva E, Bates SH, Louis GW, Jones JC, Ishida-Takahashi R, Bjorbaek C, and Myers MG Jr. Mice lacking inhibitory leptin receptor signals are lean with normal endocrine function. J. Clin. Invest. (2007) 117:1354-1360.
Soliman GA, Ishida-Takahashi R, Gong Y, Jones JC, Leshan RL, Saunders TL, Fingar DC, and Myers MG Jr. A simple qPCR-based method to detect correct insertion of homologous targeting vectors in murine ES cells. Transgenic Research (2007) In Press.