Faculty

> Sdek

Curriculum Vitae

Research Interest

My laboratory is interested in understanding the expression and regulation of enzymes involved in arachidonic acid (lipid) metabolism, and their role in the development of cardiovascular diseases. The current research interests in my laboratory are described below.

1. The paraoxonase (PON) gene family consists of three family members, PON1, PON2 and PON3. PON genes are implicated in the pathogenesis of several inflammatory diseases including atherosclerosis. Our long-term goal is to understand the physiological role of PON2 and PON3 proteins. Recent findings led us to hypothesize that PON2 protein may play a novel role in host defense and innate immunity by protecting against gram-negative microbial infection and the pathogenesis of inflammatory diseases such as atherosclerosis. We are using PON2-deficient and PON2Tg mice to test this novel hypothesis for the physiological role of PON2.

2. Defining the cardiovascular effects of COX-2-selective inhibitors has taken an increasing clinical relevance due to their recall following reports of cardiovascular side effects from their use. To determine the mechanism of COX-2 in the development of atherosclerosis, we have generated conditional COX-2 transgenic and knockout mice (together with our collaborators at UCLA). These mice are being studied to define the molecular mechanisms behind the therapeutic disadvantages of COX-2 selective inhibitors.

3. The anti- or pro-inflammatory nature of HDL function is a more sensitive indicator of the presence or absence of atherosclerosis than HDL cholesterol levels. Although a number of proteins and enzyme activities have been associated with HDL, little is known of what particular protein profiles constitute HDL function. Our laboratory utilized state of the art proteomics methodologies and identified protein signatures that distinguish pro-inflammatory HDL from anti-inflammatory HDL in animal models of atherosclerosis. We are currently characterizing and validating these proteins for i) the development of novel biomarkers for the early detection of atherosclerosis and ii) understanding the mechanisms that participate in the formation of pro-inflammatory HDL.

Representative Publications

1. Ng CJ et al. Paraoxonase-2 deficiency aggravates atherosclerosis in mice despite lower apolipoprotein-B containing lipoproteins - anti-atherogenic role for paraoxonase-2. J Biol Chem. 2006 Aug 4; [Epub ahead of print].

2. Kobayashi N, et al. Effect of Altering Dietary Omega-6: Omega-3 Fatty Acid Ratios on Prostate Cancer Membrane Composition, Cyclooxygenase-2 and Prostaglandin E-2. Clinical Cancer Research 2006, 12:4662-70.

3. Demaio L, et al. Oxidized phospholipids mediate occludin expression and phosphorylation in vascular endothelial cells. Am J Physiol Heart Circ Physiol. 2006 290(2): H674-83.

4. Reddy ST, et al. Anantharamaiah GM, Navab M, Hama S, Hough G, Grijalva V, Garber DW, Datta G, Fogelman AM.Oral amphipathic peptides as therapeutic agents. Expert Opin Investig Drugs. 2006 15(1):13-21.

5. Buga GM, et al. D-4F decreases brain arteriole inflammation and improves cognitive performance in LDL receptor null mice on a Western diet. J Lipid Res. 2006, [Epub ahead of print]

6. Anantharamiah, GM, et al. Synthetic peptides: managing lipid disorders. Curr Opin Lipidol. 2006, 17:233-237.

7. Kozak KR, et al. Characterization of serum biomarkers for detection of early stage ovarian cancer. Proteomics. 2005 5(17): 4589-4596.

8. Navab M, et al. An oral apoJ peptide renders HDL anti-inflammatory in mice and monkeys and dramatically reduces atherosclerosis in apolipoprotein E-null mice. Arterioscler Thromb Vasc Biol. 2005 25:1932-1937.

9. Ng CJ, et al. The paraoxonase gene family and atherosclerosis. Free Radic Biol Med. 2005 38: 153-163.

10. Reddy ST, et al. Potential Role for Mitogen Activated Protein Kinase Phosphatase-1 in the Development of Atherosclerotic Lesions in Mouse Models. Arterioscler. Thromb Vasc Biol. 2004 24(9): 1676-1681.