Raj Lakshman, Ph.D.

Research Professor
VA Medical Center
50 Irving St., NW, Washington, DC 20422
Phone: 202-745-8330
E-mail: raj.lakshman@med.va.gov

Research Interests

Professor Lakshman directs studies in the areas of alcoholic liver disease, coronary artery disease, metabolic and genetic obesity, and hepatotoxins.

Research Program

Alcoholism: Dr Lakshman has been carrying out pioneering research in the area of alcoholic hyperlipidemia, abnormalities in Glycoconjugates and viable biomarkers for alcohol consumption. These investigations have significant clinical implications in the diagnosis and treatment of alcohol-mediated pathology. For example, his recent findings on alcohol-induced alteration in HDL Apoprotein and phospholipids composition and their consequent effect on reverse cholesterol transport would markedly affect the cholesterol homeostasis. Furthermore, Dr. Lakshman’s group has demonstrated the specific alcohol-mediated down regulation of liver ST6Gal1 mRNA that is due to the loss of the mRNA binding protein. Thus his proposed development and validation of ST6Gal1 mRNA and/or Glycoconjugate as viable markers of alcohol consumption is essential for early diagnosis and treatment of alcoholics. Based on his innovative studies, Dr. Lakshman has discovered a new viable plasma marker for chronic alcohol consumption. If this marker were proven to have very high specificity and sensitivity, a major breakthrough would have been made for the early detection of alcohol abuse.

Atherosclerosis: Dr. Lakshman is also carrying out an important VA Merit-funded research study on the possible action of the bioflavonoid, quercetin to effectively (I) prevent the oxidation of native LDL and/or (ii) destroy oxidized LDL and/or (iii) prevent the uptake of oxidized LDL by macrophages and thereby lead to lower the incidence of atherosclerosis. Dr. Lakshman’s group has demonstrated that quercetin elicits the translocation of the mature SREBP2 from endoplasmic reticulum (ER) to the nucleus whereby it up regulates PON1 gene transcription rate and PON1 activity in a SRE-driven manner, and thereby exhibits its anti-atherogenic property. Using LDLR-/- mouse model, Dr. Lakshman’s group has demonstrated the inhibitors action of quercetin in preventing the development of atherosclerotic plaques in the aorta by “Morphometry” and by “Ultrasound Biomicroscopy”. These findings have a major clinical impact on the cardioprotective effects of quercetin.

Selected Publications

• Gong M, Garige M, Varatharajalu R, Marmillot P, Gottipati C, Leckey LC, Lakshman MR. Quercetin Up-regulates Paraoxonase 1 Gene Expression with Concomitant Protection against LDL Oxidation. Biochem Biophys Res Communication 379:1001-1004, 2009.
• Garige M, Gong M, Lakshman MR. Ethanol Destabilizes Liver ST6Gal l mRNA by Depleting a 3'-Untranslated Region Binding Protein. J Pharmacology & Experimental Therapeutics 318:1076-1082, 2006.
• Lakshman M. R., Gottipati C. S., Narasimhan S. J., Munoz J. N., Marmillot P., Nylen E. S. Inverse correlation of serum PON and homocysteine thiolactonase activities and antioxidant capacity of HDL with the severity of cardiovascular disease in type 2 diabetics. Metabolism 55:1201-1206, 2006.
• Lakshman MR, Reda MS, Materson BJ, Cushman WC, Freis ED. Diuretics & beta-blockers do not have adverse effects on plasma lipid and lipoprotein profiles in hypertensive men. Arch. Int. Med. 159, 551-558, 1999.
• Lakshman, M.R. Enzymatic conversion of beta-carotene to retinal by a cytosolic enzyme from rabbit and rat intestinal mucosa. Proc. Nat. Acad. Sci. 86:9124-9128, 1989.
• Rao MN, Ghosh P, Lakshman MR. Purification and partial characterization of cellular carotenoid binding protein from ferret liver. J. Biol. Chem. 272:24455-24460, 1997.