Srinivasa T. Reddy, Ph.D.

Laboratory Address:
3535, MRL
Los Angeles, CA 90095 CHS/BRI A8-122
650 Charles Young Drive South

Office Address:
3736 MRL

Affiliations
Affiliations
Professor In-Residence, Medicine, Molecular & Medical Pharmacology
Member, Molecular Pharmacology GPB Home Area, Molecular, Cellular & Integrative Physiology GPB Home Area
Faculty, Cardiology
Research Interests
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 lead 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.
Publications
Ganapathy Ekambaram, Su Feng, Meriwether David, Devarajan Asokan, Grijalva Victor, Gao Feng, Chattopadhyay Arnab, Anantharamaiah G M, Navab Mohamad, Fogelman Alan M, Reddy Srinivasa T, Farias-Eisner Robin D-4F, an apoA-I mimetic peptide, inhibits proliferation and tumorigenicity of epithelial ovarian cancer cells by upregulating the antioxidant enzyme MnSOD. International journal of cancer. Journal international du cancer. 2012; 130(5): 1071-81.
Navab Mohamad, Reddy Srinivasa T, Anantharamaiah G M, Hough Greg, Buga Georgette M, Danciger Jan, Fogelman Alan M D-4F-mediated reduction in metabolites of arachidonic and linoleic acids in the small intestine is associated with decreased inflammation in low-density lipoprotein receptor-null mice. Journal of lipid research. 2012; 53(3): 437-45.
Su Feng, Grijalva Victor, Navab Kaveh, Ganapathy Ekambaram, Meriwether David, Imaizumi Satoshi, Navab Mohamad, Fogelman Alan M, Reddy Srinivasa T, Farias-Eisner Robin HDL mimetics inhibit tumor development in both induced and spontaneous mouse models of colon cancer. Molecular cancer therapeutics. 2012; .
Hong Cynthia, Bradley Michelle N, Rong Xin, Wang Xuping, Wagner Alan, Grijalva Victor, Castellani Lawrence W, Salazar Jon, Realegeno Susan, Boyadjian Rima, Fogelman Alan M, Van Lenten Brian J, Reddy Srinivasa T, Lusis Aldons J, Tangirala Rajendra K, Tontonoz Peter LXRα is uniquely required for maximal reverse cholesterol transport and atheroprotection in ApoE-deficient mice. Journal of lipid research. 2012; .
Charles-Schoeman Christina, Lee Yuen Yin, Grijalva Victor, Amjadi Sogol, Fitzgerald John, Ranganath Veena K, Taylor Mihaela, McMahon Maureen, Paulus Harold E, Reddy Srinivasa T Cholesterol efflux by high density lipoproteins is impaired in patients with active rheumatoid arthritis. Annals of the rheumatic diseases. 2012; .
Watanabe Junji, Charles-Schoeman Christina, Miao Yunan, Elashoff David, Lee Yuen Yin, Katselis George, Lee Terry D, Reddy Srinivasa T Proteomic profiling following immunoaffinity capture of HDL: Association of acute phase proteins and complement factors with pro-inflammatory HDL in rheumatoid arthritis. Arthritis and rheumatism. 2012; .
Kelesidis Theodoros, Currier Judith S, Huynh Diana, Meriwether David, Charles-Schoeman Christina, Reddy Srinivasa T, Fogelman Alan M, Navab Mohamad, Yang Otto O A biochemical fluorometric method for assessing the oxidative properties of HDL. Journal of lipid research. 2011; 52(12): 2341-51.
Kim Juyong Brian, Xia Yu-Rong, Romanoski Casey E, Lee Sangderk, Meng YongHong, Shi Yi-Shou, Bourquard Noam, Gong Ke Wei, Port Zachary, Grijalva Victor, Reddy Srinivasa T, Berliner Judith A, Lusis Aldons J, Shih Diana M Paraoxonase-2 modulates stress response of endothelial cells to oxidized phospholipids and a bacterial quorum-sensing molecule. Arteriosclerosis, thrombosis, and vascular biology. 2011; 31(11): 2624-33.
Janzen Carla, Sen Suvajit, Cuevas Janis, Reddy Srinivasa T, Chaudhuri Gautam Protein phosphatase 2A promotes endothelial survival via stabilization of translational inhibitor 4E-BP1 following exposure to tumor necrosis factor-α. Arteriosclerosis, thrombosis, and vascular biology. 2011; 31(11): 2586-94.
Morgantini Cecilia, Natali Andrea, Boldrini Beatrice, Imaizumi Satoshi, Navab Mohamad, Fogelman Alan M, Ferrannini Ele, Reddy Srinivasa T Anti-inflammatory and antioxidant properties of HDLs are impaired in type 2 diabetes. Diabetes. 2011; 60(10): 2617-23.
Meriwether David, Imaizumi Satoshi, Grijalva Victor, Hough Greg, Vakili Ladan, Anantharamaiah G M, Farias-Eisner Robin, Navab Mohamad, Fogelman Alan M, Reddy Srinivasa T, Shechter Ishaiahu Enhancement by LDL of transfer of L-4F and oxidized lipids to HDL in C57BL/6J mice and human plasma. Journal of lipid research. 2011; 52(10): 1795-809.
Navab Mohamad, Reddy Srinivasa T, Anantharamaiah G M, Imaizumi Satoshi, Hough Greg, Hama Susan, Fogelman Alan M Intestine may be a major site of action for the apoA-I mimetic peptide 4F whether administered subcutaneously or orally. Journal of lipid research. 2011; 52(6): 1200-10.
Bourquard Noam, Ng Carey J, Reddy Srinivasa T Impaired hepatic insulin signalling in PON2-deficient mice: a novel role for the PON2/apoE axis on the macrophage inflammatory response. The Biochemical journal. 2011; 436(1): 91-100.
Vasquez Sergio X, Gao Feng, Su Feng, Grijalva Victor, Pope John, Martin Bill, Stinstra Jeroen, Masner Matthew, Shah Neha, Weinstein David M, Farias-Eisner Robin, Reddy Srinivasa T Optimization of microCT imaging and blood vessel diameter quantitation of preclinical specimen vasculature with radiopaque polymer injection medium. PloS one. 2011; 6(4): e19099.
Navab Mohamad, Reddy Srinivasa T, Van Lenten Brian J, Fogelman Alan M HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms. Nature reviews. Cardiology. 2011; 8(4): 222-32.
Gao Feng, Vasquez Sergio X, Su Feng, Roberts Svetlana, Shah Neha, Grijalva Victor, Imaizumi Satoshi, Chattopadhyay Arnab, Ganapathy Ekambaram, Meriwether David, Johnston Brad, Anantharamaiah G M, Navab Mohamad, Fogelman Alan M, Reddy Srinivasa T, Farias-Eisner Robin L-5F, an apolipoprotein A-I mimetic, inhibits tumor angiogenesis by suppressing VEGF/basic FGF signaling pathways. Integrative biology : quantitative biosciences from nano to macro. 2011; 3(4): 479-89.
Imaizumi Satoshi, Navab Mohamad, Morgantini Cecilia, Charles-Schoeman Christina, Su Feng, Gao Feng, Kwon Murray, Ganapathy Ekambaram, Meriwether David, Farias-Eisner Robin, Fogelman Alan M, Reddy Srinivasa T Dysfunctional high-density lipoprotein and the potential of apolipoprotein A-1 mimetic peptides to normalize the composition and function of lipoproteins. Circulation journal : official journal of the Japanese Circulation Society. 2011; 75(7): 1533-8.
Bui Peter, Imaizumi Satoshi, Beedanagari Sudheer Reddy, Reddy Srinivasa T, Hankinson Oliver Human CYP2S1 metabolizes cyclooxygenase- and lipoxygenase-derived eicosanoids. Drug metabolism and disposition: the biological fate of chemicals. 2011; 39(2): 180-90.
Devarajan Asokan, Bourquard Noam, Hama Susan, Navab Mohamad, Grijalva Victor R, Morvardi Susan, Clarke Catherine F, Vergnes Laurent, Reue Karen, Teiber John F, Reddy Srinivasa T Paraoxonase 2 deficiency alters mitochondrial function and exacerbates the development of atherosclerosis. Antioxidants & redox signaling. 2011; 14(3): 341-51.
Watson Catherine E, Weissbach Nicole, Kjems Lise, Ayalasomayajula Surya, Zhang Yiming, Chang Ih, Navab Mohamad, Hama Susan, Hough Greg, Reddy Srinivasa T, Soffer Daniel, Rader Daniel J, Fogelman Alan M, Schecter Alison Treatment of patients with cardiovascular disease with L-4F, an apo-A1 mimetic, did not improve select biomarkers of HDL function. Journal of lipid research. 2011; 52(2): 361-73.