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NEPHROLOGY
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Subramaniam Pennathur, M.B.B.S.

Research Summary:

The central theme of my research has focused on the applications of biological mass spectrometry in disease pathogenesis. A major focus of the lab has been to define the role of oxidative stress on disease pathogenesis and complications. We have utilized mass spectrometry to identify key protein and metabolite alterations in disease states and tested the hypothesis whether these alterations predict complications in animal models and humans. Our strategy has been to develop analytical techniques in animal models and validate these markers in humans and then interrogating the animal model for biological pathway relevance. Recent extension of this work has included targeted as well as unbiased metabolomic and proteomic profiling.

Link to PubMed Citations

Selected Publications:

Shu L, Park JL, Byun J, Pennathur S and Shayman JA “Decreased nitric oxide bioavailability in the α-galactosidase A knockout mouse” Journal of American Society of Nephrology (in Press) Feng S, Yang N, Pennathur S, Goodison S, Lubman DM. Enrichment of Glycoproteins using Nanoscale Chelating Concanavalin A Monolithic Capillary Chromatography. Anal Chem. 2009 Apr 14. [Epub ahead of print]

Pop-Busui R, Oral E, Raffel D, Byun J, Bajirovic V, Giri A, Kellog A, Pennathur S and Stevens M “Impact of Rosiglitazone and glyburide on nitrosative stress and myocardial blood flow regulation in type 2 diabetes” Metabolism 2009 Apr 24. [Epub ahead of print]

Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyanasundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger B, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM “Metabolomic Profiles Delineate Potential Role for Sarcosine in Prostate Cancer Progression” Nature Feb 12; 457(7231):910-4, 2009.

Okamura D, Pennathur S, Koelsch K, Lopez-Guisa J, Collins S, Febbraio M, Heinecke J Eddy A “CD36 is a key regulator of oxidative stress and promotes inflammatory pathways in hyper cholesterolemic chronic kidney disease” Journal of American Society of Nephrology 2009 Mar;20(3):495-505.

Posey K, Clegg DJ, Printz RL, Byun J, Morton GJ, Vivekanandan-Giri A, Pennathur S, Baskin DG, Heinecke JW, Woods SC, Schwartz MW, Niswender KD. “Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet”Am J Physiol Endocrinol Metab. 2009 May; 296(5):E1003-12.

Malhotra J, Miao H, Zhang K, Wolfson A, Pennathur S, Pipe S and Kaufman RJ “Antioxidants reduce endoplasmic reticulum stress and improve protein secretion" Proceedings of the National Academy of Sciences U.S.A. 2008 105:18525-18530.

Patwa, T.H., Y. Wang, F.R. Miller, S. Goodison, S. Pennathur, T.J. Barder, D.M. Lubman, "A Novel Phosphoprotein Analysis Scheme for Assessing Changes in Pre-malignant and Malignant Breast Cell Lines Using 2D Liquid Separations, Protein Microarrays and Tandem Mass Spectrometry", Proteomics - Clinical Applications 2008;3(1):51-66.

Song B, Scheuner D, Ron D, Pennathur S and Kaufman RJ “Chop deletion reduces oxidative stress, improves beta cell function, and promotes cell survival in multiple mouse models of diabetes”, Journal of Clinical Investigation 2008 Oct;118 (10):3378-89.

Green PS, Vaisar T, Pennathur S, Kulstad JJ, Moore AB, Marcovina S, Brunzell J, Knopp RH, Zhao X-Q and Heinecke JW. “Combined Statin and Niacin Therapy Remodels the HDL Proteome”, Circulation 2008 Sep 16; 118(12):1259-67.

Vivekanandan-Giri A, Wang JH, Byun J, Pennathur S. “Mass spectrometric quantification of amino acid oxidation products identifies oxidative mechanisms of diabetic end-organ damage”, Reviews in Endocrine and Metabolic Disorders (2008) 9:275-287.

Zhang H, Saha, J, Byun J, Schin M, Lorenz M, Kennedy R, Kretzler M, Fedman, E, Pennathur S and Brosius FC “Rosiglitazone Reduces Renal and Plasma Markers of Oxidative Injury and Reverses Urinary Metabolite Abnormalities in the Amelioration of Diabetic Nephropathy” , American Journal of Physiology-Renal Physiology, Oct 2008; 295: F1071-1081.

Wiggin TD, Kretzler M, Pennathur S, Sullivan KA, Brosius FC and Feldman EL “Rosiglitazone Treatment Reduces Diabetic Neuropathy in STZ treated DBA/2J mice”, Endocrinology Oct 2008; 149: 4928-4937.

Qian Y, Feldman E, Pennathur S, Kretzler M, Brosius FC. From Fibrosis to Sclerosis: Mechanisms of Glomerulosclerosis in Diabetic Nephropathy, Diabetes 57(6):1439-45, 2008.

Pennathur S, Heinecke JW “Oxidative Stress and Endothelial Dysfunction in vascular disease ” Current Diabetes Reports 7(4):257-64, 2007.

Pennathur S , Heinecke JW “Role of oxidative stress in the pathogenesis of diabetic vascular disease” Antioxidants and Redox Signaling 9(7):955-969, 2007.

Vaisar T*, Pennathur S* , Green P, Gharib SA, Hoofnagle AN, Cheung MC, Byun J, Vuletic S, Kassim S, Singh P, Chea H, Knopp RH, Brunzell J, Geary R, Chait A, Brown G, Zhao X-Q, Elkon K, Marcovina S, Ridker P, Oram J, Heinecke JW “Shotgun Proteomics Implicates Protease Inhibition and Complement Activation in the Anti-inflammatory Properties of HDL ” Journal of Clinical Investigation 117(3):746-756, 2007. *Both authors contributed equally

Brosius FC, Hostetter T, Kelepouris E, Mitsnefes MM, Moe SM, Moore MA, Pennathur S, Smith GL, Wilson P ‘Detection of Chronic Kidney Disease in Patients With or at Increased Risk of Cardiovascular Disease’ Circulation Sep 5;114(10):1083-7, 2006 and Reprinted in Hypertension. Oct; 48(4):751-5, 2006.

Takeshita J, Byun J, Nhan TQ, Pritchard D, Pennathur S, Schwartz SM, Chait A and Jay W. Heinecke ‘Myeloperoxidase generates 5-Chlorouracil in human atherosclerotic tissue: A Potential Pathway for Somatic Mutagenesis by Macrophages’ Journal of Biological Chemistry Feb 10;281(6):3096-104, 2006.

Gurer-Orhan H, Ercal N, Mare S, Pennathur S, Orhan H and Heinecke JW ‘Misincorporation of free meta-tyrosine into cellular proteins: a potential cytotoxic mechanism for oxidized amino acids’ Biochemical Journal 395(2):277-84, 2006.

Choi D , Pennathur S, Perier C, Tieu K, Tiesman P, Wu D, Jackson-Lewis V, Vila M, Vonsatte J Heinecke JW, Prezedborski S ‘ Ablation of the inflammatory enzyme myeloperoxidase mitigates features of Parkinson's disease in mice’ Journal of Neuroscience 25(28):6594-600, 2005.

Pennathur S , Ido Y, Heller J, Williamson J, Heinecke JW ‘A Species Resembling Hydroxyl Radical Damages the Retina in Diabetes: Potential Role of a Carbonyl/Polyunsaturated Fatty Acid Pathway’ Journal of Biological Chemistry, Jun 17; 280(24):22706-14, 2005.

Lamharzi N, Renard C, Kramer F, Pennathur S, Heinecke JW, Chait A, Bornfeldt KE ‘Hyperlipidemia in concert with hyperglycemia stimulates the proliferation of macrophages in atherosclerotic lesions: Potential role of glucose-oxidized LDL ’ Diabetes 53(12):3217-25 2004.

Pennathur S , Bergt C, Shao B, Byun J, Kassim SY Singh P, McDonald T, Brunzell J, Chait A, Oram J , O’Brien K, Geary RL, Heinecke JW ‘Human Atherosclerotic Intima and Blood of Patients with Established Coronary Artery Disease Contain High Density Lipoprotein Damaged by Reactive Nitrogen Species ” Journal of Biological Chemistry 279(41):42977-83, 2004.

Bergt C*, Pennathur S*, Fu X, Byun J, Singh P, McDonald T, O’ Brien K, Chait A, Brunzell J, Geary RL, Oram JF, Heinecke JW ‘ The myeloperoxidase product hypochlorous acid oxidizes HDL in the human artery wall and impairs ABCA1-dependent cholesterol transport” Proceedings of the National Academy of Sciences U.S.A . 101(35):13032-7, 2004. *Both authors contributed equally

Pennathur S, Heinecke JW ‘Mechanisms of Oxidative Stress in Diabetes: Implications for the Pathogenesis of Vascular Disease and Antioxidant Therapy’, Frontiers in Biosciences Vol 9, 565-574, 2004.

 
     
   

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