V. Subbaiah, Ph.D.
Office and Laboratory Location:
University of Illinois at Chicago, Department of Medicine
Section of Endocrinology, Diabetes and Metabolism
1819 West Polk St., M/C 640
Chicago, IL 60612
BS - Andhra University, India
MS - Nagpur University, India
PhD - Indian Institute of Science, India
1. Lecithin: cholesterol acyltransferase (LCAT): LCAT is a critical component of the reverse cholesterol transport pathway. It is essential for the formation and maturation of HDL in plasma. Our research focuses on a) the role of the substrate and positional specificities of LCAT in determining the atherosclerosis susceptibility, and b) the role of LCAT in the metabolism of oxidized phospholipids, platelet activating factor, and steroid hormones.
2. Sphingomyelin (SM). SM is the second most important phospholipid in the lipoproteins, and is a critical component of plasma membranes of all cells. Our research focuses on the elucidation of the physiological function of SM as the modulator of lipase and phospholipase activities, inhibitor of lipid peroxidation in membranes and lipoproteins, as regulator of cellular cholesterol metabolism, and as modulator of the inflammatory response. The role of sphingolipids in insulin signaling is another area of interest.
3. Role of trans double bonds in lipids: Most of the naturally occurring double bonds in lipids are of cis configuration. Introduction of a trans double bond either through chemical processing of food or through certain bacterial action, results in profound effects on membrane structure and function. Our research interest is to determine the effect of trans double bond on membrane raft function, gene transcription, and cell signaling mechanisms.
4. Mechanism of action of conjugated linoleic acids (CLA): Although CLA in diet have been shown to have several beneficial effects (including ant-obesity, anti-inflammatory, anti-cancer effects), the exact mechanism of their action is unclear. The two major dietary CLA, 9cis 11trans CLA and 10 trans 12 cis CLA have been shown to exert completely different biological effects. We are studying the effects of various CLA isomers on the membrane structure and function, with a view to design the optimum structure that would retain the beneficial effects of CLA, without the undesirable effects such as insulin resistance. The effect of various CLA isomers on the distribution of insulin receptor in the raft and non-raft domains, on the signaling pathways of insulin, and on glucose transport are being investigated.
Research Team: 312 996 0212
Selected Recent Publications and Manuscripts in
Goyal J, Wang K, Liu M and Subbaiah PV. Novel function of lecithin-cholesterol acyltransferase. Hydrolysis of oxidized polar phospholipids generated during lipoprotein oxidation. J Biol Chem 272:16231-16239, 1997
Subbaiah PV. Determination and Clinical Significance of Phospholipids. Handbook of Lipoprotein Testing. Ed. N Rifai, R WArnick, MH Dominiczak. AACC Press (1997) pp 415-429.
Subbaiah PV, Subramanian
VS and Liu M. Trans unsaturated fatty acids inhibit lecithin-cholesterol
acyltransferase, and alter its positional specificity. J Lipid Res 39:1438-1447,
Subbaiah PV, Subramanian VS and Wang K. Novel physiological function of sphingomyelin in plasma: Inhibition of lipid peroxidation in low density lipoproteins. J Biol Chem 274:36409-36414,1999.
Wang K and Subbaiah PV. Importance of the free sulfhydryl groups of lecithin-cholesterol acyltransferase for its sensitivity to oxidative inactivation. Biochim Biophys Acta 1488:268-277,2000.
Gesquiere L, Cho W and Subbaiah PV. Role of Group IIa and Group V Secretory Phospholipases A2 in the Metabolism of Lipoproteins. Substrate specificities of the enzymes and the regulation of their activities by sphingomyelin. Biochemistry 41:4911-4920,2002.
Wang K and Subbaiah PV. Role of the interfacial binding domain in the oxidative susceptibility of lecithin: Cholesterol acyltransferase. Biochem J 365:649-657,2002.
Subbaiah PV, Billington SJ, Jost BH, Songer JG, and Lange Y. Sphingomyelinase D, a novel probe for cellular sphingomyelin: Effects on cholesterol homeostasis in human skin fibroblasts. J Lipid Res 44:1574-1580,2003.
Sargis RM and Subbaiah PV. Trans unsaturated fatty acids are less oxidizable than cis unsaturated fatty acids and protect endogenous lipids from oxidation in lipoproteins and lipid bilayers. Biochemistry 41:11533-11543,2003.
Subbaiah PV, Sowa JM and Davidson MH. Evidence for altered positional specificity of LCAT in vivo: Increased synthesis of saturated cholesteryl esters after dietary supplementation with docosahexaenoic acid. J Lipid Res 45:2245-2251,2004.
Subbaiah PV, Gesquiere LR and Wang K. Regulation of selective uptake of cholesteryl esters from the high density lipoproteins by sphingomyelin . J Lipid Res 46:2699-2705,2005.
Subbaiah PV, Horvath, P, and Achar, SB. Regulation of the activity and fatty acid specificity of lecithin-cholesterol acyltransferase by sphingomyelin and its metabolites, ceramide and ceramide phosphate. Biochemistry 45: 5029-5038, 2006
Sargis RM, and Subbaiah PV . Protection of membrane cholesterol by sphingomyelin against free radical-mediated oxidation . Free Rad Biol Med 40: 2092-2102, 2006
Sircar D, and Subbaiah PV. IsoprostaneMeasurement in Plasma and Urine by Liquid Chromatography–Mass Spectrometry with One-Step Sample Preparation. Clin. Chem.,53: 251 – 258, 2007.
Singh DK, and Subbaiah PV. Modulation of the activity and arachidonic acid selectivity of group X secretory phospholipase A2 by sphingolipids. J.Lipid Res. 48: 683-692, 2007.
Singh DK. Gesquiere, GR, and Subbaiah PV. Role of sphingomyelin and ceramide in the regulation of the activity and fatty acid specificity of group V secretory phospholipase A2. Arch. Biochem. Biophys., 459: 280-287, 2007.
Lucic D, Huang ZH, Gu D, Subbaiah PV, and Mazzone T. Cellular sphingolipids regulate macrophage apolipoprotein E secretion. Biochemistry 46: 11196-11204,2007
Chen S, and Subbaiah PV . Phospholipid and fatty acid specificity of endothelial lipase: Potential role of the enzyme in the delivery of docosahexaenoic acid (DHA) to tissues. Biochim. Biophys. Acta, 1771: 1319-1328, 2007
Subbaiah PV. Pathophysiology of sphingomyelin: Role in sterol homeostasis, inflammation and atherosclerosis. In “Bioactive Phospholipids: Role in Inflammation and Atherosclerosis” Ed by A.Tselepis. Transworld Research Network, 2008.
Subbaiah PV, Singh DK, and Sowa JM. Sphingolipids and cellular cholesterol homeostasis. Effect of ceramide on cholesterol trafficking and HMG CoA reductase activity. Arch. Biochem. Biophys. 474: 32-28, 2008.