Molecular and cellular mechanisms regulating glucose homeostasis, type 2 diabetes, and breast cancer.
Ph.D., Case Western Reserve University
The long-term goal of my research is to understand the underlying molecular and cellular mechanisms regulating glucose homeostasis as they relate to type 2 diabetes and breast cancer progression. Specifically, I am investigating factors involved in the reorganization of the cytoskeleton during glucose transport in adipocytes. The major defect in type 2 diabetes is insulin resistance of peripheral tissues, primarily skeletal muscle and adipose tissue. Insulin-stimulated glucose uptake requires the activation of several signaling pathways to mediate the translocation of insulin-responsive glucose transporter 4 (GLUT4) vesicles from an intracellular pool to the plasma membrane. Identification and characterization of factors involved in glucose uptake is critical for developing more effective treatments for type 2 diabetes. My laboratory has identified myosin II, calpain 10, and naringenin as critical regulators of insulin-stimulated glucose uptake. My lab also focuses on the mechanisms cancer cells use to promote proliferation and survival. Cancer cells often have altered metabolism to support cell proliferation and survival. We have identified a component in grapefruit that impairs the proliferation and survival of breast cancer cells as well as alters metabolism. We propose to characterize the mechanism of action of this component as an initial step to its use in a clinical setting.
Ramos, J., Hatkewich, T., Eanes, L., Santos-Sanchez, I. and Patel, Y. M. Naringenin Inhibits Proliferation and Survival of Tamoxifen‐Resistant Breast Cancer Cells. Breast Cancer – From Biology to Medicine. http://dx.doi.org/10.5772/66698
Eanes, L. and Patel Y. M. Naringenin Targets Multiple Signaling Pathways in Tamoxifen-Resistant MCF-7 Breast Cancer Cells. Biochimie Open 3:(2016) 64-71
Stall, R., Boseman, A., Yang, J., LaJeunesse, D., and Patel, Y.M. High Resolution Helium Ion Microscopy of 3T3-L1 Adipocytes. JSM Nanotechnol Nanomed 2(2):(2014) 1027.
Hatkevich, T., Ramos, J., Santos-Sanchez, I. and Patel, Y. M. A naringenin-tamoxifen combination impairs cell proliferation and survival of MCF-7 breast cancer cells. Exp Cell Res. 327(2):(2014) 331-339.
Stall, R., Ramos, J., Fulcher, F. K. and Patel, Y. M. Regulation of Myosin IIA and Filamentous Actin during Insulin-Stimulated Glucose Uptake in 3T3-L1 Adipocytes. Exp Cell Res. 322:(2014) 81-88.
Woody, S., Stall, R., Ramos, J. and Patel, Y. M. Regulation of Myosin Light Chain Kinase during Insulin-Stimulated Glucose Uptake in 3T3-L1 Adipocytes. PLoS One. 2013 Oct 8;8(10):e77248.
Fulcher, F. K., Smith, B. T., Russ, M. and Patel, Y. M. Dual Role for Myosin II in GLUT4-Mediated Glucose Uptake in 3T3-L1 Adipocytes. Exp Cell Res. 314:(2008) 3264-3274.
Turner, M. D., Fulcher, F. K., Velasquez, C. R., Smith, B. T., Aganna, E., Partridge, C. J., Hitman, G. A., Clark, A. and Patel, Y. M. Calpain facilitates actin reorganization during glucose-stimulated insulin secretion. Biochem. Biophys. Res. Commun. 352:(2007) 650-655.
Steimle, P. A., Fulcher, F. K. and Patel, Y. M. A novel role for myosin II in insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Biochem. Biophys. Res. Commun. 331:(2005) 1560-1565.
Cooke, D. W. and Patel Y. M. GLUT4 expression in 3T3-L1 adipocytes is repressed by proteasome inhibition. Mol Cell Endocrinol. 232:(2005) 37-45.
Walton, F. S., Harmon, A. W., Paul, D. S., Drobná, Z., Patel, Y. M. and Styblo, M. Inhibition of Insulin Dependent Glucose Uptake by Methylated Trivalent Arsenicals: Possible Mechanism of Arsenic-Induced Diabetes Toxicol Appl Pharmacol. 198:(2004) 424-433.
Harmon, A. W., Paul, D. S. and Patel, Y. M. MEK inhibitors impair insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Am J Physiol Endocrinol Metab. 287:(2004) E758-E766
Harmon, A. W. and Patel, Y. M. Naringenin inhibits glucose uptake in MCF-7 breast cancer cells: a mechanism for impaired cellular proliferation. Breast Cancer Res Treat. 85:(2004) 103-110.
Cole, K. A., Harmon, A. W., Harp, J. B. and Patel, Y. M. Rb regulates C/EBPβ-DNA-binding activity during 3T3-L1 adipogenesis. Am J of Physiol Cell Physiol 286:(2004) C349-C354.
Paul, D. S., Harmon, A. W., Winston, C. P. and Patel, Y. M. Calpain facilitates GLUT4 vesicle translocation during insulin-stimulated glucose uptake in adipocytes. Biochem J. 376:(2003) 625-632.
Harmon, A. W. and Patel, Y. M. Naringenin inhibits Phosphoinositide 3-Kinase activity and glucose uptake in 3T3-L1 adipocytes. Biochem. Biophys. Res. Commun. 305:(2003) 229-234.
Styblo M., Waters S.B., Drobná Z., Lin S., Walton F.S., Jaspers I., Patel Y.M., Del Razo L.M., Thomas D.J. (2003) Production and biological significance of methylated trivalent arsenicals. International Symposium on Bio-Trace Elements (2002) 10/28-11/2, Tokyo, Japan.
Harmon, A. W., Y. M. Patel and J. B. Harp. Genistein inhibits CCAAT/enhancer binding protein beta (C/EBPbeta) activity and 3T3-L1 adipogenesis by increasing C/EBP homologous protein (CHOP) expression. Biochem J. 367:(2002) 203-208.
Patel, Y. M. and Lane, M. D. Mitotic clonal expansion during preadipocyte differentiation: calpain- mediated turnover of p27. J. Biol. Chem. 275:(2000) 17653-17660.
Patel, Y. M. and Lane, M. D. Role of calpain in adipocyte differentiation. Proc. Natl. Acad. Sci. USA 96:(1999) 1279-1284.
Gurney, A. L., Park, E. A., Liu, J., Giralt, M., McGrane, M. M., Patel, Y. M., Savon, S. and Hanson, R. W. Metabolic regulation of gene transcription. J. Nutr. 124 (Suppl):(1994) 1533S-1539S.
Hanson, R. W. and Patel, Y. M. Phosphoenolpyruvate carboxykinase (GTP): The gene and the enzyme. Advances in Enzymology & Related Areas of Molecular Biology. 69:(1994) 203-281.
Patel, Y. M., Yun, J. S., Liu, J., McGrane, M. M. and Hanson, R. W. An analysis of regulatory elements in the phosphoenolpyruvate carboxykinase (GTP) gene which are responsible for its tissue-specific and metabolic control in transgenic mice. J. Biol. Chem. 269:(1994) 5619-5628.
Friedman, J. E., Yun, J. S., Patel, Y. M., McGrane, M. M. and Hanson, R. W. Glucocorticoids regulate the induction of phosphoenolpyruvate carboxykinase (GTP) gene transcription during diabetes. J. Biol. Chem. 268:(1993) 12952-12957.
McGrane, M. M., Yun, J. S., Patel, Y. M. and Hanson, R. W. Metabolic control of gene expression: in vivo studies with transgenic mice. Trends Biochem. Sci. 17:(1992) 40-44.
Undergraduate Research (BIO 499)
Metabolic Regulation in Health and Disease (BIO 535)
Hormones in Action (BIO 578)
Molecular Biological Approaches in Research (BIO 596)
Seminar in Molecular Cell Biology (BIO 609)