Professor, Department of Biochemistry
Professor, Department of Medicine
The Charron Laboratory works on two classes of proteins that play critical roles in regulation of glucose homeostasis and energy balance. Specifically, we study role of the glucose transporters GLUT4 and GLUT8 and also the glucagon receptor (Gcgr) in glucose homeostasis and insulin sensitivity. Using transgenic and targeted gene strategies, we have generated mouse models to define the role of these proteins in cellular and whole body metabolism and energy balance. The incidence of diabetes and obesity has reached epidemic proportions and treatment and diagnostic strategies are inadequate. The complications of diseases of insulin resistance are vast and include heart attack and stroke. In addition to genetic factors, the incidence of diabetes and obesity are influenced by environmental factors such as diet and exercise. Strong evidence derived from experimental animal models and human epidemiology suggests that perturbation of the early developmental environment (e.g. nutrient, stress, toxins) has lasting effects that enhance the offspring’s susceptibility to metabolic and other diseases. It is thought that these effects are mediated through alterations in the epigenome. Alterations in DNA methylation are measured as they represent the most stable epigenomic modifications. Mouse models are being used to evaluate the influence of maternal diet and metabolic status on the fetal/neonatal epigenome. The stability of these epigenetic signatures and their association with disease incidence are under investigation. A prospective clinical study has begun to evaluate the impact of a common environmental toxicant on DNA methylation profiles in umbilical cord and peripheral blood T cells and subsequent development of childhood obesity. We hope to identify an epigenetic signature of increased risk for obesity that may be used for early diagnosis and intervention. The ultimate goal of our studies is to define the molecular mechanism(s) underlying the pathogenesis of diabetes and obesity that may lead to novel therapeutics and potential cures for these and related metabolic diseases.
Vuguin, P.M., M.H. Kedees, L. Cui, Y. Guz, R.W. Gelling, M. Nejathaim, M.J. Charron and G. Teitelman. Ablation of the glucagon receptor gene increases fetal lethality, and produces alterations in islet development and maturation. Endo. 147:3995-4006 (2006). PMID: 16627579
Ranalletta, M., X.Q. Du, Y. Seki, A.S. Glenn, M. Kruse, A. Fiallo, I. Estrada, T.-S. Tsao, A.E. Stenbit, E.B. Katz and M.J. Charron. Hepatic response to restoration of GLUT4 in skeletal muscle of GLUT4 null mice. Am. J. Phys. 293(5):E1178-1187 (2007). PMID: 17711992
Longuet, C., E.M. Sinclair, A. Maida, L.L. Maziarz, M.J. Charron and D.J. Drucker. The glucagon receptor is required for the adaptive metabolic response to fasting. Cell Metabolism 8:359-371 (2008).
Berglund, E.D., R.S. Lee-Young, D.G. Lustig, S.G. Lynes, E.P. Donahue, R.C. Camacho, M.E. Meredith, M.A. Magnuson, M.J. Charron and D.H. Wasserman. Hepatic energy state is regulated by glucagon receptor signaling in mice. J. Clin. Invest. 119:2412-2422 (2009). PMID: 19662685
Gelling, R.W., P.M. Vuguin, X.Q. Du, L. Cui, J. Romer, R.A. Pederson, M. Leiser, H. Sørensen, J.J. Holst, C. Fedelius, P.B. Johansen, N. Fleischer, C.H.S. McIntosh, E. Nishimura and M.J. Charron. Pancreatic beta-cell overexpression of the glucagon receptor gene results in enhanced b-cell function and mass. Am. J. Physiol. (Endo Metab) 297(3):E695-707(2009). PMID: 19602585
Hartil, K., P.M. Vuguin, M. Kruse, E. Schmuel, A. Fiallo, C. Vargas, M.J. Warner, J.L. Durand, L.A. Jelicks and M.J. Charron. Maternal substrate utilization programs the development of the metabolic syndrome in male mice exposed to high fat in utero. Peds. Res. 66:368-373 (2009). PMID: 19581843
Wang, M-y, L. Chen, G.O. Clark, Y. Lee, R.D. Stevens, O.R. Ilkayeva, B.R. Wenner, J.R. Bain, M.J. Charron, C.B. Newgard, and R.H. Unger. Leptin therapy in insulin-deficient type I diabetes. Proc. Natl. Acad. Sci. 107:4813-4819 (2010). PMID: 20194735
Berglund, E.D., L. Kang, R.S. Lee-Young, C.M. Hansenour, D.G. Lustig, S.G. Lynes, E.P. Donahue, L.L. Swift, M.J. Charron and D.H. Wasserman. Glucagon and lipid interactions in the regulation of hepatic AMPK signaling and expression of PPAR alpha and FGF21 transcripts in vivo. Am. J. Physiol. Endo. Met. 299:E607-14 (2010). PMID: 20663988
Berglund, E.D. D.G. Lustig, R.A. Beheza, C.M. Hasenour, R.S. Lee-Young, E.P. Donahue, S.E. Lynes, L.L. Swift, M.J. Charron, B.M. Damon and D.H. Wasserman. Hepatic glucagons action is essential for exercise-induced reversal of mouse fatty liver. Diabetes 60:2720-2729 (2011). PMID:21885872
Lee, Y., M.-Y. Wang, X.Q. Du, M.J. Charron and R.H. Unger. Glucagon receptor knockout prevents insulin deficient type 1 diabetes in mice. Diabetes 60:391-397 (2011).
Ali, S., B.J. Lamont, M.J. Charron and D.J. Drucker. Plasticity in the incretin axis revealed through dual elimination of the murine Gcgr and Glp1r. J. Clin. Invest. 121:1917-1929(2011).
Vuguin P.M. and M.J. Charron. Novel insight into glucagon receptor action: lessons from knockout and transgenic mouse models. Diabetes, Obesity and Metabolism. 13 (Suppl. 1):144-150 (2011).
Buyuk, E., N. Santoro, H.W. Cohen, M.J. Charron* and S. Jindal*. Reduced neurotrophin receptor TrkA expression in human granulosa cells: A novel marker of diminishing ovarian reserve. Fert. and Sterility 96:474-478 (2011). (* indicates equal contribution). PMID: 21645891
S. Ouhilal, P.M. Vuguin, L. Cui, X.Q. Du, R.W. Gelling, S. Reznik, R. Russell, A.F. Parlow, C. Karpovsky, N. Santoro and M.J. Charron. Hypoglycemia, hyperglucagonemia and feto-placental defects in glucagon receptor knockout mice: a role for glucagon action in pregnancy maintenance. Am J Physiol Endocrinol Metab. 302(5):E522-531 (2012). PMID: 22167521
Seki, Y.,L. Williams, PM Vuguin and M.J. Charron. Epigenetic programming of diabetes and obesity: animal models. Endo. 153:1031-38 (2012). PMID: 22253432
Grigoryan, M., M.H. Kedees, M.J. Charron, Y. Guz and G. Teitelman. Regulation of mouse intestinal L cell progenitors proliferation by the glucagon family of peptides. Endo. 153:3076-3088 (2012). PMID:22569789
Lee, Y., E.D. Berglund, M.Y. Wang, X. Fu, X. Yu, M.J. Charron, S.C. Burgess and R.H. Unger. Metabolic manifestation of insulin deficiency do not occur without glucagon action. Proc. Natl. Acad., Sci. USA 109:14792-14976 (2012). PMID:22891336
Longuet, C., A.M. Robledo, D. Dean, C. Dai, S. Ali, I. McGuinness, V. de Chavez, P.M. Vuguin, M.J. Charron, A.C. Powers and D.J. Drucker. Liver-specific disruption of the murine glucagon receptor produces alpha-cell hyperplasia: Evidence for a circulating a-cell growth factor. Diabetes (2012, in press). PMID:23160527
Berger, J.H., M.J. Charron and D.L. Silver. Major facilitator superfamily domain-containing protein 2a (MFSD2A) has roles in body growth, motor function, and lipid metabolism. PLoS One 7(11):e50629 (2012). PMID:23209793
Mighiu, P.I., J.T.Y. Yue, B.M. Filippi, M.A. Abraham, M. Chari, C.K.L. Lam, C.S. Yang, N.R. Christian, M.J. Charron and T.K.T. Lam. Hypothalamic glucagon signaling inhibits glucose production. Nature Medicine (2013, in press).
More Information About Dr. Maureen Charron
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Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Forchheimer Building, Room 312
Bronx, NY 10461