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Thomas Pulinilkunnil

PhD (UBC)


Assistant Professor

Adjunct Professor (UNB)
Affiliate Scientist (SJRH)
Department member since 2012

Saint John, NB
506-636-6973
tpulinil@dal.ca
Lab Homepage

Research:

Nutrient regulation of lysosome metabolism, signaling and autophagy in health and disease; Amino acid biology and energy metabolism


Research Areas

Proteotoxic Basis for Metabolic Heart Disease

One of the major focus of the Pulinilkunnil laboratory is to assess how adaptive or causative changes in protein synthesis and degradation causes heart disease. To maintain cellular homeostasis, synthesized proteins are degraded and recycled inside cellular organelles called lysosomes by a process known as autophagy. Using a multispecies approach (rodents, yeast and zebrafish) Pulinilkunnil lab will specifically examine how different nutrients (glucose, fat and amino acids) influence lysosomal function to alter autophagy. Furthermore investigate whether aberrant lysosomal function impact mitochondrial metabolism and energetics thus governing cardiovascular outcomes in biology and disease.

Lysosome Nutrient Sensing and Metabolism in Cancer Pathogenesis

Reprogrammed energetics and metabolism is an emerging hallmark of cancer cells. Indeed, altered mitochondrial fuel metabolism contributes to oncogenic mutations which in turn influences cellular signaling and function. Numerous oncogenic processes that are resistant to chemotherapeutics are found to exhibit features of intermittent oxygen and nutrient deprivation, mitochondrial stress, abnormal cell growth and suppressed cellular death. Recent studies have shown that abnormalities in cellular metabolism augment autophagy to facilitate cancer cells to precipitously adapt to environmental stressors by sustaining uninterrupted proliferation thereby evading demise by radiation and/or chemotherapy. Our laboratory is currently elucidating the mechanism by which tumor cell metabolism signals changes in lysosomal autophagy and mechanisms by which this signaling could influence the outcomes of treating cancer. By specifically examining the cross talk between mitochondria and lysosome we hope to uncover novel biochemical pathways that could be targeted selectively to render cancer cells susceptible to first line cancer treatment.

Biology of ER Glycosylation in Health and Disease

Glycosylation is an extremely important function by which all human cells build sugar chains or glycans that are subsequently attached to other functional molecules, including proteins and lipids. The products of these attachments are called glycoproteins or glycolipids, and are required for the normal growth and function of all tissues and organs. Impairment in glycosylating enzyme disrupts glycan synthesis and metabolism leading to congenital disorder of glycosylation (CDG). Using yeast and zebrafish models Pulinilkunnil lab aims to examine molecular pathways by which impaired glycosylation promotes intracellular distress specifically in organelles like mitochondria, endoplasmic reticulum and lysosomes that are mainly responsible for generating energy, performing quality check on proteins and degrading cellular waste. This research will identify and characterize novel pathways and proteins mediating pathological effects of defective glycosylation.

Cardiotoxic Effect of Aquatic Pollutants

Aquatic pesticide are endocrine disruptor that continues to persist in the environment despite being discontinued and is associated with increased risks of neurodegenerative disease and breast cancer. Pulinilkunnil laboratory is examining transcriptomic signaling regulating autophagy and mitochondrial energetics in heart, liver, fat and skeletal muscle to aquatic toxicants using zebrafish model

Keywords:
Perfusion, Electrophoresis, Polarography, Transgenesis, Transduction, FACS, Isotope labelling, FPLC, In vivo Imager

Graduate Students

Andrew Cowie PhD
Logan Slade MSc
Purvi Trivedi PhD

Honours Students

Luke Duffley BSc (2017)
Marija Velajinovska BSc (2017)

Lab Personnel

Lester Perez Research Associate (Nov 2015)
Liliam Rios Research Technician (Oct 2016)
Kathleen Tozer Medical Student (May 2016)

Former Lab Members

Purvi Trivedi 2016 PhD Canada
Tess Robarts 2014 Summer Student (May-Aug)
Alyson Zwicker 2014 Summer Student (May-Aug)
Brandyn Chase 2013 Medical Student (Apr-Aug)
Kelan Kennedy 2013 Medical Student (Apr-Aug)
Alex Morris 2013 Medical Student (Apr-Aug)

Publications

  1. Trivedi PC, Bartlett JJ, Perez LJ, Brunt KR, Legare JF, Hassan A, Kienesberger PC, Pulinilkunnil T., (2016) Glucolipotoxicity diminishes cardiomyocyte TFEB and inhibits lysosomal autophagy during obesity and diabetes Biochim Biophys Acta. 1861(12 Pt A):1893-1910 [PubMed]
  2. Bartlett JJ, Trivedi PC, Yeung P, Kienesberger PC, Pulinilkunnil T., (2016) Doxorubicin Impairs Cardiomyocyte Viability by Suppressing Transcription Factor EB Expression and Disrupting Autophagy Biochem J. BCJ20160385: [PubMed]
  3. Dubé JJ, Sitnick MT, Schoiswohl G, Wills RC, Basantani MK, Cai L, Pulinilkunnil T, Kershaw EE., (2015) Adipose triglyceride lipase deletion from adipocytes, but not skeletal myocytes, impairs acute exercise performance in mice. Am J Physiol Endocrinol Metab. : [PubMed]
  4. O'Neill HM, Lally JS, Galic S, Pulinilkunnil T, Ford RJ, Dyck JR, van Denderen BJ, Kemp BE, Steinberg GR., (2015) Skeletal muscle ACC2 S212 phosphorylation is not required for the control of fatty acid oxidation during exercise. Physiol Rep. 3:e12444 [PubMed]
  5. Schoiswohl G, Stefanovic-Racic M, Menke MN, Wills RC, Surlow BA, Basantani MK, Sitnick MT, Cai L, Yazbeck CF, Stolz DB, Pulinilkunnil T, O'Doherty RM, Kershaw EE., (2015) Impact of Reduced ATGL-Mediated Adipocyte Lipolysis on Obesity-Associated Insulin Resistance and Inflammation in Male Mice. Endocrinology. 156:3610-3624 [PubMed]
  6. Kraus D, Yang Q, Kong D, Banks AS, Zhang L, Rodgers JT, Pirinen E, Pulinilkunnil TC, Gong F, Wang YC, Cen Y, Sauve AA, Asara JM, Peroni OD, Monia BP, Bhanot S, Alhonen L, Puigserver P, Kahn BB., (2014) Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity Nature 00:00 [PubMed]
  7. Zordoky BN, Nagendran J, Pulinilkunnil T, Kienesberger PC, Masson G, Waller TJ, Kemp BE, Steinberg GR, Dyck JR., (2014) AMPK-dependent inhibitory phosphorylation of ACC is not essential for maintaining myocardial fatty acid oxidation. Circ Res. 115:518-524 [PubMed]
  8. O'Neill HM, Lally JS, Galic S, Thomas M, Azizi PD, Fullerton MD, Smith BK, Pulinilkunnil T, Chen Z, Samaan MC, Jorgensen SB, Dyck JR, Holloway GP, Hawke TJ, van Denderen BJ, Kemp BE, Steinberg GR., (2014) AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice. Diabetologia :1693-702 [PubMed]
  9. Adisesh A, Melville S, Pulinilkunnil T, Lutchmedial S, Brunt KR., (2014) Holiday reading. Diving into the ice bucket challenge. CMAJ 186:1404-5 [PubMed]
  10. Pulinilkunnil T, Kienesberger PC, Nagendran J, Waller TJ, Young ME, Kershaw EE, Korbutt G, Haemmerle G, Zechner R, Dyck JR., (2013) Myocardial Adipose Triglyceride Lipase Overexpression Protects Diabetic Mice From the Development of Lipotoxic Cardiomyopathy. Diabetes. 62(5):1464-77 [PubMed]
  11. Kienesberger PC, Pulinilkunnil T, Nagendran J, Dyck JR., (2013) Myocardial triacylglycerol metabolism. J Mol Cell Cardiol. 55:101-10. [PubMed]
  12. Nagendran J, Kienesberger PC, Pulinilkunnil T, Zordoky BN, Sung MM, Kim T, Young ME, Dyck JR., (2013) Cardiomyocyte specific adipose triglyceride lipase overexpression prevents doxorubicin induced cardiac dysfunction in female mice Heart 99:1041-47 [PubMed]
  13. Kienesberger PC, Pulinilkunnil T, Nagendran J, Young ME, Bogner-Strauss JG, Hackl H, Khadour R, Heydari E, Haemmerle G, Zechner R, Kershaw EE, Dyck JR, (2013) Early structural and metabolic cardiac remodelling in response to inducible adipose triglyceride lipase ablation Cardiovasc Res. 99:442-51 [PubMed]
  14. Pulinilkunnil T, Kienesberger PC, Nagendran J, Sharma N, Young ME, Dyck JR., (2013) Cardiac-specific adipose triglyceride lipase overexpression protects from cardiac steatosis and dilated cardiomyopathy following diet-induced obesity. Int J Obes (Lond). in press.: [PubMed]
  15. Fullerton MD, Galic S, Marcinko K, Sikkema S, Pulinilkunnil T, Chen ZP, O'Neill HM, Ford RJ, Palanivel R, O'Brien M, Hardie DG, Macaulay SL, Schertzer JD, Dyck JR, van Denderen BJ, Kemp BE, Steinberg GR., (2013) Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin. Nat Med : [PubMed]
  16. Sitnick MT, Basantani MK, Cai L, Schoiswohl G, Yazbeck CF, Distefano G, Ritov V, DeLany JP, Schreiber R, Stolz DB, Gardner NP, Kienesberger PC, Pulinilkunnil T, Zechner R, Goodpaster BH, Coen P, Kershaw EE., (2013) Skeletal muscle triacylglycerol hydrolysis does not influence metabolic complications of obesity. Diabetes 62:3350-61 [PubMed]
  17. Nagendran J, Pulinilkunnil T, Kienesberger PC, Sung MM, Fung D, Febbraio M, Dyck JR., (2013) Cardiomyocyte-specific ablation of CD36 improves post-ischemic functional recovery. J Mol Cell Cardiol. 63:180-88 [PubMed]
  18. Willis MS, Bevilacqua A, Pulinilkunnil T, Kienesberger P, Tannu M, Patterson C, (2013) The role of ubiquitin ligases in cardiac disease J Mol Cell Cardiol 00:00 [PubMed]
  19. Nagendran J, Pulinilkunnil T, Kienesberger PC, Sung MM, Fung D, Febbraio M, Dyck JR, (2013) Cardiomyocyte-specific ablation of CD36 improves post-ischemic functional recovery J Mol Cell Cardiol 63:180-188 [PubMed]
  20. Kienesberger PC, Pulinilkunnil T, Nagendran J, Dyck JR., (2012) Myocardial triacylglycerol metabolism. J Mol Cell Cardiol. 55:101-10 [PubMed]
  21. Pulinilkunnil, T, Nagendran, J, and Dyck JR, (2012) AMPK and Metabolic Remodeling in Cardiac Disease Translational Cardiology Molecular Basis of Cardiac Metabolism, Cardiac Remodeling, Translational Therapies and Imaging Techniques, C.Patterson, M.S. Willis (Eds) :113
  22. Kienesberger PC, Pulinilkunnil T, Sung MM, Nagendran J, Haemmerle G, Kershaw EE, Young ME, Light PE, Oudit GY, Zechner R, Dyck JR., (2012) Myocardial ATGL overexpression decreases the reliance on fatty acid oxidation and protects against pressure overload-induced cardiac dysfunction. Mol Cell Biol. 32(4):740-50. [PubMed]
  23. Puthanveetil P, Wang Y, Zhang D, Wang F, Kim MS, Innis S, Pulinilkunnil T, Abrahani A, Rodrigues B., (2011) Cardiac triglyceride accumulation following acute lipid excess occurs through activation of a FoxO1-iNOS-CD36 pathway. Free Radic Biol Med. 51(2):352-363 [PubMed]
  24. Pulinilkunnil T, He H, Kong D, Asakura K, Peroni OD, Lee A, Kahn BB., (2011) Adrenergic regulation of AMP-activated protein kinase in brown adipose tissue in vivo. J Biol Chem 286(11):8798-8809 [PubMed]
  25. Hamming KS, Soliman D, Webster NJ, Searle GJ, Matemisz LC, Liknes DA, Dai XQ, Pulinilkunnil T, Riedel MJ, Dyck JR, Macdonald PE, Light PE., (2010) Inhibition of beta-cell sodium-calcium exchange enhances glucose-dependent elevations in cytoplasmic calcium and insulin secretion. Diabetes 59(7):1686-1693 [PubMed]
  26. Olson DP, Pulinilkunnil T, Cline GW, Shulman GI, Lowell BB., (2010) Gene knockout of Acc2 has little effect on body weight, fat mass, or food intake. Proc Natl Acad Sci U S A 107(16):7598-603 [PubMed]
  27. Durgan DJ, Pulinilkunnil T, Villegas-Montoya C, Garvey ME, Frangogiannis NG, Michael LH, Chow CW, Dyck JR, Young ME., (2010) Ischemia/reperfusion tolerance is time-of-day-dependent: mediation by the cardiomyocyte circadian clock. Circ Res. 106(3):546-550 [PubMed]
  28. Tsai JY, Kienesberger PC, Pulinilkunnil T, Sailors MH, Durgan DJ, Villegas-Montoya C, Jahoor A, Gonzalez R, Garvey ME, Boland B, Blasier Z, McElfresh TA, Nannegari V, Chow CW, Heird WC, Chandler MP, Dyck JR, Bray MS, Young ME., (2010) Direct regulation of myocardial triglyceride metabolism by the cardiomyocyte circadian clock. J Biol Chem 285(5):2918-2929 [PubMed]
  29. Pulinilkunnil T, Puthanveetil P, Kim MS, Wang F, Schmitt V, Rodrigues B., (2010) Ischemia-reperfusion alters cardiac lipoprotein lipase. Biochim Biophys Acta. 1801(2):171-175 [PubMed]
  30. Folmes KD, Chan AY, Koonen DP, Pulinilkunnil TC, Baczkó I, Hunter BE, Thorn S, Allard MF, Roberts R, Gollob MH, Light PE, Dyck JR., (2009) Distinct early signaling events resulting from the expression of the PRKAG2 R302Q mutant of AMPK contribute to increased myocardial glycogen. Circ Cardiovasc Genet 2(5):457-466 [PubMed]
  31. Kienesberger PC, Lee D, Pulinilkunnil T, Brenner DS, Cai L, Magnes C, Koefeler HC, Streith IE, Rechberger GN, Haemmerle G, Flier JS, Zechner R, Kim YB, Kershaw EE., (2009) Adipose triglyceride lipase deficiency causes tissue-specific changes in insulin signaling. J Biol Chem. 284(44):30218-29. [PubMed]
  32. Xue B*, Pulinilkunnil T*, Murano I, Bence KK, He H, Minokoshi Y, Asakura K, Lee A, Haj F, Furukawa N, Catalano KJ, Delibegovic M, Balschi JA, Cinti S, Neel BG, Kahn BB. (*-Co First Authors), (2009) Neuronal protein tyrosine phosphatase 1B deficiency results in inhibition of hypothalamic AMPK and isoform-specific activation of AMPK in peripheral tissues. Mol Cell Biol. 29(16):4563-73. [PubMed]
  33. Puthanveetil P, Wang F, Kewalramani G, Kim MS, Hosseini-Beheshti E, Ng N, Lau W, Pulinilkunnil T, Allard M, Abrahani A, Rodrigues B., (2008) Cardiac glycogen accumulation after dexamethasone is regulated by AMPK. Am J Physiol Heart Circ Physiol. 295(4):H1753-62. [PubMed]
  34. Kewalramani G, An D, Kim MS, Ghosh S, Qi D, Abrahani A, Pulinilkunnil T, Sharma V, Wambolt RB, Allard MF, Innis SM, Rodrigues B., (2007) AMPK control of myocardial fatty acid metabolism fluctuates with the intensity of insulin-deficient diabetes. J Mol Cell Cardiol. 42(2):333-342 [PubMed]
  35. Ghosh S, Kewalramani G, Yuen G, Pulinilkunnil T, An D, Innis SM, Allard MF, Wambolt RB, Qi D, Abrahani A, Rodrigues B., (2006) Induction of mitochondrial nitrative damage and cardiac dysfunction by chronic provision of dietary omega-6 polyunsaturated fatty acids. Free Radic Biol Med. 41(9):1413-1424 [PubMed]
  36. Qi D, Kuo KH, Abrahani A, An D, Qi Y, Heung J, Kewalramani G, Pulinilkunnil T, Ghosh S, Innis SM, Rodrigues B., (2006) Acute intralipid infusion reduces cardiac luminal lipoprotein lipase but recruits additional enzyme from cardiomyocytes. Cardiovasc Res. 72(1):124-133 [PubMed]
  37. Pulinilkunnil T, Rodrigues B., (2006) Cardiac lipoprotein lipase: metabolic basis for diabetic heart disease. Cardiovasc Res. 69(2):329-340 [PubMed]
  38. An D, Kewalramani G, Chan JK, Qi D, Ghosh S, Pulinilkunnil T, Abrahani A, Innis SM, Rodrigues B., (2006) Metformin influences cardiomyocyte cell death by pathways that are dependent and independent of caspase-3. Diabetologia. 49(9):2174-2189 [PubMed]
  39. Pulinilkunnil T, An D, Ghosh S, Qi D, Kewalramani G, Yuen G, Virk N, Abrahani A, Rodrigues B., (2005) Lysophosphatidic acid-mediated augmentation of cardiomyocyte lipoprotein lipase involves actin cytoskeleton reorganization. Am J Physiol Heart Circ Physiol. 288(6):H2802-10 [PubMed]
  40. Ghosh S, Pulinilkunnil T, Yuen G, Kewalramani G, An D, Qi D, Abrahani A, Rodrigues B., (2005) Cardiomyocyte apoptosis induced by short-term diabetes requires mitochondrial GSH depletion. Am J Physiol Heart Circ Physiol. 289(2):H768-76 [PubMed]
  41. An D, Pulinilkunnil T, Qi D, Ghosh S, Abrahani A, Rodrigues B., (2005) The metabolic "switch" AMPK regulates cardiac heparin-releasable lipoprotein lipase. Am J Physiol Endocrinol Metab. 288(1):E246-53 [PubMed]
  42. Pulinilkunnil T, An D, Yip P, Chan N, Qi D, Ghosh S, Abrahani A, Rodrigues B., (2004) Palmitoyl lysophosphatidylcholine mediated mobilization of LPL to the coronary luminal surface requires PKC activation. J Mol Cell Cardiol. 37(5):931-938 [PubMed]
  43. Ghosh S, Qi D, An D, Pulinilkunnil T, Abrahani A, Kuo KH, Wambolt RB, Allard M, Innis SM, Rodrigues B., (2004) Brief episode of STZ-induced hyperglycemia produces cardiac abnormalities in rats fed a diet rich in n-6 PUFA. Am J Physiol Heart Circ Physiol. 287(6):H2518-27 [PubMed]
  44. Qi D, Pulinilkunnil T, An D, Ghosh S, Abrahani A, Pospisilik JA, Brownsey R, Wambolt R, Allard M, Rodrigues B., (2004) Single-dose dexamethasone induces whole-body insulin resistance and alters both cardiac fatty acid and carbohydrate metabolism. Diabetes 53(7):1790-7. [PubMed]
  45. Ghosh S, An D, Pulinilkunnil T, Qi D, Lau HC, Abrahani A, Innis SM, Rodrigues B., (2004) Role of dietary fatty acids and acute hyperglycemia in modulating cardiac cell death. Nutrition 20(10):916-923 [PubMed]
  46. Pulinilkunnil T, Qi D, Ghosh S, Cheung C, Yip P, Varghese J, Abrahani A, Brownsey R, Rodrigues B, (2003) Circulating triglyceride lipolysis facilitates lipoprotein lipase translocation from cardiomyocyte to myocardial endothelial lining. Cardiovasc Res. 59(3):788-97. [PubMed]
  47. Pulinilkunnil T, Abrahani A, Varghese J, Chan N, Tang I, Ghosh S, Kulpa J, Allard M, Brownsey R, Rodrigues B., (2003) Evidence for rapid "metabolic switching" through lipoprotein lipase occupation of endothelial-binding sites. J Mol Cell Cardiol. 35(9):1093-1103 [PubMed]