Srinivasa T. Reddy, Ph.D.

Laboratory Address:
A-8 122 CHS
650 Charles E. Young Drive South
Los Angeles, CA 90095 43-153 CHS

Office Address:
43-144 CHS

Affiliations
Affiliations
Professor In-Residence, Medicine, Obstetrics and Gynecology, Molecular & Medical Pharmacology
Member, California NanoSystems Institute, Interdepartmental Program in Molecular Toxicology, Molecular Biology Institute, 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

A selected list of publications:

Dodani S, Kaeley G S, Arora S, Reddy S T   Coronary artery disease in high risk South Asian immigrants: Role of dysfunctional HDL in risk prediction Indian heart journal, ; 69(5): 658-659.
Guirgis Faheem W, Dodani Sunita, Leeuwenburgh Christiaan, Moldawer Lyle, Bowman Jennifer, Kalynych Colleen, Grijalva Victor, Reddy Srinivasa T, Jones Alan E, Moore Frederick A   HDL inflammatory index correlates with and predicts severity of organ failure in patients with sepsis and septic shock PloS one, 2018; 13(9): e0203813.
Singh Rajan, Pervin Shehla, Lee Se-Jin, Kuo Alan, Grijalva Victor, David John, Vergnes Laurent, Reddy Srinivasa T   Metabolic profiling of follistatin overexpression: a novel therapeutic strategy for metabolic diseases Diabetes, metabolic syndrome and obesity : targets and therapy, 2018; 11: 65-84.
Mukherjee Pallavi, Hough Greg, Chattopadhyay Arnab, Grijalva Victor, O'Connor Ellen Ines, Meriwether David, Wagner Alan, Ntambi James M, Navab Mohamad, Reddy Srinivasa T, Fogelman Alan M   Role of enterocyte stearoyl-Co-A desaturase-1 in LDLR-null mice Journal of lipid research, 2018; 59(10): 1818-1840.
Charles-Schoeman C, Gugiu G B, Ge H, Shahbazian A, Lee Y Y, Wang X, Furst D E, Ranganath V K, Maldonado M, Lee Terry, Reddy S T   Remodeling of the HDL proteome with treatment response to abatacept or adalimumab in the AMPLE trial of patients with rheumatoid arthritis Atherosclerosis, 2018; 275: 107-114.
Guirgis Faheem W, Leeuwenburgh Christiaan, Grijalva Victor, Bowman Jennifer, Kalynych Colleen, Moldawer Lyle, Moore Frederick A, Reddy Srinivasa T   HDL Cholesterol Efflux is Impaired in Older Patients with Early Sepsis: A Subanalysis of a Prospective Pilot Study Shock (Augusta, Ga.), 2018; 50(1): 66-70.
Morgantini C, Trifirò S, Tricò D, Meriwether D, Baldi S, Mengozzi A, Reddy S T, Natali A   A short-term increase in dietary cholesterol and fat intake affects high-density lipoprotein composition in healthy subjects Nutrition, metabolism, and cardiovascular diseases : NMCD, 2018; 28(6): 575-581.
Li Wei, Kennedy David, Shao Zhili, Wang Xi, Kamdar Andre Klaassen, Weber Malory, Mislick Kayla, Kiefer Kathryn, Morales Rommel, Agatisa-Boyle Brendan, Shih Diana M, Reddy Srinivasa T, Moravec Christine S, Tang W H Wilson   Paraoxonase 2 prevents the development of heart failure Free radical biology & medicine, 2018; 121: 117-126.
Chattopadhyay Arnab, Yang Xinying, Mukherjee Pallavi, Sulaiman Dawoud, Fogelman Hannah R, Grijalva Victor, Dubinett Steven, Wasler Tonya C, Paul Manash K, Salehi-Rad Ramin, Mack Julia J, Iruela-Arispe M Luisa, Navab Mohamad, Fogelman Alan M, Reddy Srinivasa T   Treating the Intestine with Oral ApoA-I Mimetic Tg6F Reduces Tumor Burden in Mouse Models of Metastatic Lung Cancer Scientific reports, 2018; 8(1): 9032.
Charles-Schoeman Christina, Meriwether David, Lee Yuen Yin, Shahbazian Ani, Reddy Srinivasa T   High levels of oxidized fatty acids in HDL are associated with impaired HDL function in patients with active rheumatoid arthritis Clinical rheumatology, 2018; 37(3): 615-622.
Devarajan Asokan, Su Feng, Grijalva Victor, Yalamanchi Meghna, Yalamanchi Ashna, Gao Feng, Trost Hannah, Nwokedi Josephine, Farias-Eisner Gina, Farias-Eisner Robin, Fogelman Alan M, Reddy Srinivasa T   Paraoxonase 2 overexpression inhibits tumor development in a mouse model of ovarian cancer Cell death & disease, 2018; 9(3): 392.
Guirgis Faheem W, Dodani Sunita, Moldawer Lyle, Leeuwenburgh Christiaan, Bowman Jennifer, Kalynych Colleen, Jones Alan E, Reddy Srinivasa T, Moore Frederick A   Exploring the Predictive Ability of Dysfunctional High-Density Lipoprotein for Adverse Outcomes in Emergency Department Patients with Sepsis: A Preliminary Investigation Shock (Augusta, Ga.), 2017; 48(5): 539-544.
Mukherjee Pallavi, Hough Greg, Chattopadhyay Arnab, Navab Mohamad, Fogelman Hannah R, Meriwether David, Williams Kevin, Bensinger Steven, Moller Travis, Faull Kym F, Lusis Aldons J, Iruela-Arispe M Luisa, Bostrom Kristina I, Tontonoz Peter, Reddy Srinivasa T, Fogelman Alan M   Transgenic tomatoes expressing the 6F peptide and ezetimibe prevent diet-induced increases of IFN-β and cholesterol 25-hydroxylase in jejunum Journal of lipid research, 2017; 58(8): 1636-1647.
Singh Rajan, Braga Melissa, Reddy Srinivasa T, Lee Se-Jin, Parveen Meher, Grijalva Victor, Vergnes Laurent, Pervin Shehla   Follistatin Targets Distinct Pathways To Promote Brown Adipocyte Characteristics in Brown and White Adipose Tissues Endocrinology, 2017; 158(5): 1217-1230.
Charles-Schoeman Christina, Yin Lee Yuen, Shahbazian Ani, Wang Xiaoyan, Elashoff David, Curtis Jeffrey R, Navarro-Millán Iris, Yang Shuo, Chen Lang, Cofield Stacey S, Moreland Larry W, Paulus Harold, O'Dell James, Bathon Joan, Louis Bridges S, Reddy Srinivasa T   Improvement of High-Density Lipoprotein Function in Patients With Early Rheumatoid Arthritis Treated With Methotrexate Monotherapy or Combination Therapies in a Randomized Controlled Trial Arthritis & rheumatology (Hoboken, N.J.), 2017; 69(1): 46-57.
Cedó Lídia, García-León Annabel, Baila-Rueda Lucía, Santos David, Grijalva Victor, Martínez-Cignoni Melanie Raquel, Carbó José M, Metso Jari, López-Vilaró Laura, Zorzano Antonio, Valledor Annabel F, Cenarro Ana, Jauhiainen Matti, Lerma Enrique, Fogelman Alan M, Reddy Srinivasa T, Escolà-Gil Joan Carles, Blanco-Vaca Francisco   ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer Scientific reports, 2016; 6: 36387.
Sharma Salil, Ruffenach Grégoire, Umar Soban, Motayagheni Negar, Reddy Srinivasa T, Eghbali Mansoureh   Role of oxidized lipids in pulmonary arterial hypertension Pulmonary circulation, 2016; 6(3): 261-73.
Meriwether David, Sulaiman Dawoud, Wagner Alan, Grijalva Victor, Kaji Izumi, Williams Kevin J, Yu Liqing, Fogelman Spencer, Volpe Carmen, Bensinger Steven J, Anantharamaiah G M, Shechter Ishaiahu, Fogelman Alan M, Reddy Srinivasa T   Transintestinal transport of the anti-inflammatory drug 4F and the modulation of transintestinal cholesterol efflux Journal of lipid research, 2016; 57(7): 1175-93.
Mehta Niyati U, Grijalva Victor, Hama Susan, Wagner Alan, Navab Mohamad, Fogelman Alan M, Reddy Srinivasa T   Apolipoprotein E-/- Mice Lacking Hemopexin Develop Increased Atherosclerosis via Mechanisms That Include Oxidative Stress and Altered Macrophage Function Arteriosclerosis, thrombosis, and vascular biology, 2016; 36(6): 1152-63.
Chattopadhyay Arnab, Navab Mohamad, Hough Greg, Grijalva Victor, Mukherjee Pallavi, Fogelman Hannah R, Hwang Lin H, Faull Kym F, Lusis Aldons J, Reddy Srinivasa T, Fogelman Alan M   Tg6F ameliorates the increase in oxidized phospholipids in the jejunum of mice fed unsaturated LysoPC or WD Journal of lipid research, 2016; 57(5): 832-47.