William L. Lowe Jr., MD Associate Professor Medicine IGF-I Gene Expression and Genetics of Diabetes Curricula: Cell Biology Molecular Biology and Genetics E-mail:   wlowe@northwestern.edu

My laboratory has three areas of interest.

(1) To help elucidate the mechanism for the increased incidence of atherosclerosis in patients with diabetes, my laboratory is investigating the effect of glucose on vascular cell function. The ability of glucose to activate signal transduction pathways and the role of those signaling pathways in vascular cell migration and proliferation are being examined. Special emphasis is being placed on glucose-induced activation of the mitogen-activated protein kinases (MAPKs). An additional goal of these studies is to identify glucose-regulated genes in vascular cells and define the role of the glucose-activated signaling pathways in modulating expression of these genes.

(2) Type 2 diabetes is a complex disorder secondary to changes in insulin secretion and sensitivity. Patient populations with a probable defect in insulin secretion are being recruited for genetic studies to facilitate identification of susceptibility genes for type 2 diabetes. Both candidate gene and linkage analyses will be used to address this problem. Potential candidate genes important for insulin secretion are being sequenced to identify polymorphisms that may alter protein function and increase susceptibility to type 2 diabetes.

(3) My laboratory has a longstanding interest in the regulation of insulin-like growth factor-I (IGF-I) gene expression. A function of IGF-I is to mediate the growth-promoting effects of growth hormone, although little is known about the molecular mechanisms by which growth hormone regulates IGF-I gene expression. Model systems employing hepatocytes in primary culture are being used to address this important question.

Publications:

da Silva. B., Gapstur, S.M., Achenbach, Y.H., Schuh, T.S., Kotlar, T.S., Liu, K., and Lowe, Jr., W.L. (2000) Lack of Association Between the -308 Polymorphism of the Tumor Necrosis Factor-Alpha Gene and the Insulin Resistance Syndrome. J. Investig. Med., 48:236-244. 2000.

Liu, W., Schoenkerman, A., and Lowe, Jr., W.L. (2000) Activation of Members of the Mitogen-Activated Protein Kinase Family by Glucose in Endothelial Cells. Am. J. Physiol. (In press).

Benbassat, C., L.N.N. Shoba, M. Newman, M.L. Adamo, S.J. Frank, and W.L. Lowe, Jr. (1999) Growth Hormone-Mediated Regulation of Insulin-Like Growth Factor I Promoter Activity in C6 Glioma Cells. Endocrinology. 140:3073-3081.

Shoba, L., M.R. An, S.J. Frank, and W.L. Lowe, Jr. (1999) Developmental Regulation of Insulin-Like Growth Factor-I and Growth Hormone Receptor Gene Expression. Mol Cell Endocrinol. 152:125-136.

View Publications by Bill Lowe listed in the National Library of Medicine (PubMed).

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