Current Research:
The major research emphasis of our laboratory is to understand the role of the growth hormone (GH)/ growth hormone receptor (GHR) axis in health and disease. The GH-GHR axis plays a critical permissive role in the pathogenesis of certain chronic microvascular complications of diabetes mellitus (DM). The projects currently underway in the laboratory focus on the molecular mechanisms regulating expression of the GHR gene in diabetes mellitus. We have identified and characterized the various cis-elements and their cognate trans-acting factors that play a role in the regulation of the GHR gene in DM. Our recent results support a role for fatty acids (FA) n the regulation of expression of GHR. We are currently investigating the molecular basis for FA’s effect on GHR expression. Parallel studies in the laboratory have also identified the glomerular podocyte as a target of GH action. The cellular basis for the effects of GH on the podocyte actin cytoskeleton is the focus of ongoing projects. The understanding of these mechanisms may permit the identification of pharmacophores designed to alter GH action in a tissue-specific manner and thus potentially abolish the development of certain complications of DM such as nephropathy. Other areas of research in the laboratory relate to the functional analysis of a novel member of the insulin family of proteins (Insulin-like peptide 6; Insl6) that was recently cloned in our laboratory. This protein is maximally expressed in the germ cell of the testes and our preliminary findings support a role for this secreted protein in Sertoli cell function.
Representative Publications:
Kasik J, Muglia L, Stephan DA, and Menon RK. "Identification, Chromosomal Mapping and Partial Characterization of Mouse Insl6: A New Member of the Insulin Family." Endocrinology, 2000; 141(1): 458-61.
Lu C, Schwartzbauer G, Sperling MA, Devaskar SU, Thamotharan S, Robbins PD, McTiernan CF, Liu J-L, Jiang J, Frank SJ, Menon RK. "Demonstration of Direct Effects of Growth Hormone on Neonatal Cardiomyocytes." J Biol Chem, 2001; 276 (25): 22892-22900.
Gowri PM, Yu JH, Shaufl A, Sperling MA, Menon RK. "Recruitment of a Repressosome Complex at the GHR Promoter and its Potential Role in Diabetic Nephropathy." Mol Cell Biol, 2003; 23 (3): 815-825.
Rajakumar A, Thamotharan S, Raychaudhuri N, Menon RK, Devaskar SU. "Trans-Activators Regulating Neuronal Glucose Transporter Isoform-3 Gene Expression in Mammalian Neurons." J Biol Chem, 2004;279 26768-26779.
Held MA, Cosme-Blanco W, Difedele LM, Bonkowski EL, Menon RK, Denson LA. "Alterations in Growth Hormone Receptor Abundance Regulate Growth Hormone Signaling in Murine Obstructive Cholestasis." Am J Physiol Gastrointest Liver Physiol, 2005; 288(5):G986-93.
DiFederle, LM, He J, Bonkowski EL, Han X, Held, MA, Bohan A, Menon RK, Denson LA. "Tumor Necrosis Factor Alpha Blockade Restores Growth Hormone Signaling in Murine Colitis." Gastroenterology, 2005; 128(5):1278-91.
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