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Department of Chemistry and Biochemistry
California State University, Northridge
Northridge, California, 91330-8262
telephone: (818) 677-7737
fax: (818) 677-4068
Office: Citrus Hall 3112B
My overall research interest is in the area of lipoprotein metabolism and atherosclerosis. It is well known that abnormal plasma low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol levels result in cardiovascular disease. We are interested in the molecular and cellular mechanisms that translate an anomalous lipoprotein profile into atherosclerotic lesions. We are studying various components of the atherogenesis pathway including apolipoproteins, lipases and lipoprotein receptors. The current emphasis is on understanding cellular events that are unique to the vessel wall and may initiate lesion formation.
We are investigating two lipases, viz. lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL). Both lipases hydrolyze the triglyceride component of plasma chylomicrons and very low density lipoprotein (VLDL) particles and contribute to cholesterol homeostasis. Recent studies have established that LPL and HTGL also function as apoproteins and ligands for lipoprotein receptors, associate with lipoprotein particles and hepatic lipoprotein receptors, and thereby enhance lipoprotein catabolism and clearance.
In a related study, we are employing in vitro studies in cultured cells to examine the cellular mechanisms of cholesterol efflux from cultured macrophages. A recently discovered cell surface transport protein called ABCA1 was shown to be responsible for apolipoprotein A-I mediated cholesterol efflux. Our studies are aimed at dissecting this cellular transport pathway and identifying its requirements.
In a separate investigation we are studying why diabetics are predisposed to premature atherosclerosis. The prevalence of glycated and oxidized lipoproteins in diabetics has been implicated for their cardiovascular complications. We believe that in addition to contributing toward cellular cholesterol accumulation, modified lipoproteins may modulate the expression of various genes in the vascular wall leading up to lesion formation. We will examine if diabetic conditions of hyperglycemia, hyperinsulinemia and hypertriglyceridemia enhance the expression various pro-atherosclerotic genes.
A relatively new member of the nuclear receptor gene family, PPAR-gamma, has been associated with atherosclerosis and obesity. A number of molecular processes are altered upon activation of PPAR-gamma by specific ligands, which include lipid- and glucose-lowering pharmaceutical agents. We have recently identified 4 novel isoforms of the PPAR-gamma transcript in macrophages. Our purpose is to evaluate the functional differences between these isoforms using mammalian expression vectors specific for individual isoforms.
All of these research projects will provide a better understanding of the biochemical basis for the development and progression of cardiovascular disease.
"Activation of peroxisome proliferator activated receptor gamma results in an atheroprotective apolipoprotein profile in HepG2 cells" Dahabreh, D.F. and Medh, J.D. Advances in Biological Chemistry, 2012, 2(3), 218.
"Regulation of translational efficiency by disparate 5'-UTRs of PPAR-gamma splice variants" McClelland, S., Shrivastava R. and Medh, J.D. PPAR Research [Online], 2009, Article ID 193413.
"Down-regulation of lipoprotein lipase increases glucose uptake in L6 muscle cells" Lopez, V., Saraff, K. and Medh, J.D. Biochemical and Biophysical Research Communications, 2009, 389, 34.
"Genetics and Molecular Biology: Phospholipid transfer protein in atherogenesis" Akopian, D., and Medh, J.D. Current Opinion in Lipidology, 2006, 17, 695-698.
"Simultaneous isolation of total cellular lipids and RNA from cultured cells" Akopian, D. and Medh, J.D., Biotechniques, 2006, 41, 426-430.
"Role of acyl CoA: cholesterol acyl transferase (ACAT) in atherogenesis" Akopian, D. and Medh, J.D. Current Opinion in Lipidology, 2006, 17, 85-88.
"Identification and regulation of novel peroxisome proliferator activated receptor-gamma splice variants in human THP-1 macrophages" Chen, Y., Jimenez, A., and Medh, J.D. Biochem Biophy Acta, 2006, 1759, 32-43.
"Genetic analysis of four novel peroxisome proliferator activated receptor splice variants in monkey macrophages" Zhou, J., Wilson, K.M., and Medh, J.D. Biochem Biophy Res Comm., 2002, 292, 274-283.
"A role for lipid-binding protein in atherosclerosis" Medh, J.D. Curr Opin in Lipidology 2002, 13, 93-95.
"Macrophage-specific expression of human lipoprotein lipase accelerates atherosclerosis in transgenic apoE knock-out but not in C57BL/6 mice" Wilson, K., Fry, G. L., Chappell, D. A, Sigmund, C. D., and Medh, J. D. Atherosclerosis, Thrombosis and Vascular Biology 2001, 21, 1809-1815.
"Lipoprotein lipase and hepatic lipase promote receptor-mediated catabolism of lipoproteins by an apolipoprotein E-dependent mechanism" Medh, J. D., Fry, G. L., Bowen, S. L., Ruben, S., Wong, H., and Chappell, D. A. J. Lipid Res. 2000, 41, 1858-1871.
"ABC1: The Defect in Tangier Disease and Familial HDL Deficiency" Medh, J. D. Curr. Opin. in Lipidol. 2000, 325-327.
"Hepatic Lipase binds to the Low Density Lipoprotein Receptor and induces the catabolism of Remnant particles" Medh, J. D., Fry, G. L., Bowen, S. L., Ruben, S., Hill, J., Wong, H., and Chappell, D. A. J. Lipid Res. 1999, 40, 1263-1275.
"Peroxisome proliferator-activated receptors in atherosclerosis" Medh J. D. Curr. Opinion Lipidol. 1999, 10, 69-71.
"Recent Insights into Receptor-Mediated Mechanisms of Lipoprotein Remnant Catabolism" Chappell, D. A. and Medh, J. D. Prog. Lipid Res. 1998, 37, 393-422.
"Lipoprotein lipase binds to low density lipoprotein receptors and induces receptor-mediated catabolism of very low density lipoproteins in vitro" Medh, J. D., Bowen, S. L., Fry, G. L., Ruben, S., Andracki, M. E., Inoue, I., Lalouel, J-M., Strickland, D. K., and Chappell, D. A., J. Biol. Chem. 1996, 271, 17073-17080.
"The 39-kDa receptor-associated protein modulates lipoprotein catabolism by binding to LDL receptors" Medh, J. D., Fry, G. L., Bowen, S. L., Pladet, M. W., Strickland, D. K., and Chappell, D. A., J. Biol. Chem. 1995, 270, 536-540.