Faculty Profiles

 

Current Research:

Research in the Myers lab focuses on the biology of leptin, a hormone that regulates physiological processes relevant to diabetes and the metabolic syndrome. Adipocytes secrete leptin to convey information about nutritional and metabolic status by activating the leptin receptor (LRb) on certain neurons in the brain. These neurons regulate metabolism (including glycemic control) and endocrine function. Mutation of leptin or LRb in rodents and humans results in profound diabetes, metabolic syndrome, and endocrine failure. The lab takes a broad-based approach to understanding leptin action by defining the mechanisms of cellular LRb action, studying the neurons that express LRb, and determining the roles of these molecular and neural mediators in leptin action /in vivo/.

 

The lab has already learned a great deal about the mechanisms of LRb signaling, as well as the roles of individual LRb signals in the physiologic response to leptin, and continues to explore specific questions about cellular mechanisms of leptin action. Current areas of focus include roles for Jak2, STAT5, and regulators of the proteasome in leptin action. The Myers lab continues to study these mechanisms in cultured cells in addition to examining their physiologic roles in genetically modified mouse models.

 

While two well studied populations of LRb-expressing neurons in the arcuate nucleus of the hypothalamus mediate important aspects of leptin action, these neurons only account for a fraction of leptin action; indeed they only comprise approximately 20% of all LRb-expressing neurons in the brain. The Myers lab is therefore scrutinizing several other major populations of LRb neurons in the brain; the function of these novel populations of LRb-expressing neurons is likely to be relevant to diabetes and other aspects of the metabolic syndrome and endocrine function.

 

It is also clear that leptin controls the early development of at least some of the neural populations that are involved in the control of glucose homeostasis and metabolism. This developmental regulation may be involved in the programming of the predisposition to diabetes and the metabolic syndrome. The lab is developing genetic models that will facilitate the interrogation of the mechanisms and consequences of this leptin-mediated neural programming.

 

Overall, by studying the molecular, cellular, neural and developmental functions of leptin and by understanding the contribution of each of these processes to leptin action, The Myers lab aims to define the mechanisms by which leptin regulates metabolism and how their alteration may contribute to diabetes and other metabolic disorders.

 

 

Recent Publications:

 

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.* LRbàSTAT3 signaling is required for the neuroendocrine regulation of energy expenditure. Diabetes (2004) 53(12):

 

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's Metabolic Actions. Cell Metabolism (2006) 4:49-60.

 

Bodary PF, Shen Y, Ohman M, Bahrou KL, Vargas FB, Cudney SS, Wickenheiser KJ, *Myers MG Jr*, and Eitzman DT. Leptin regulates neointima formation following arterial injury through mechanisms independent of blood pressure and the leptin receptor/STAT3 signaling pathways involved in energy homeostasis. ATVB (2007): 70-76.

 

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.

 

Li Z, Zhou Y, Carter-Su C, *Myers MG Jr*, and Rui L. SH2B1 enhances leptin signaling by both Jak2 Y813 phosphorylation-dependent and --independent mechanisms. Mol. Endo (2007), In Press.

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