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James Donald McCully, PhD

James McCully Phd
Academic Title:
Associate Professor of Surgery
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Biography

Dr. McCully’s research focuses on the mechanisms and subcellular localization of the biochemical and molecular events contributing to myocardial cell death. In particular, his lab has investigated the discriminant and/or coordinate mechanisms leading to ischemia/reperfusion injury in the neonate, child, mature and aged male and female with particular emphasis on the development of novel and specific cardioprotective protocols. 

Recently he has developed a novel approach to cardioprotection using autologous mitochondrial transplantation. His research has demonstrated that transplantation of autogeneic mitochondria into the ischemic zone of the myocardium during early reperfusion significantly enhances post-ischemic functional recovery. These studies have shown that the transplanted mitochondria act externally and then are internalized by myocardial cells to provide myocellular rescue and cardioprotection. The transplanted mitochondria upregulate cytokines associated with enhanced post-infarct cardiac function and improvement of cardiac remodeling and upregulate protein pathways associated with the generation of precursor metabolites for energy and cellular respiration with no immune or auto-immune response. The transplanted mitochondria are internalized through actin-dependent endocytosis and rescue cell function by increasing ATP content and oxygen consumption rate. Significantly, he has demonstrated that internalized mitochondria replace depleted or damaged mitochondrial (mt) DNA.

Publications

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  1. Cowan DB, Yao R, Akurathi V, Snay ER, Thedsanamoorthy JK, Zurakowski D, Ericsson M, Friehs I, Wu Y, Levitsky S, Del Nido PJ, Packard AB, McCully JD. Intracoronary Delivery of Mitochondria to the Ischemic Heart for Cardioprotection. PLoS One. 2016; 11(8):e0160889.
  2. McCully JD, Levitsky S, Del Nido PJ, Cowan DB. Mitochondrial transplantation for therapeutic use. Clin Transl Med. 2016 Mar; 5(1):16.
  3. Bautista-Hernandez V, Karamanlidis G, McCully JD, Del Nido PJ. Cellular and Molecular Mechanisms of Low Cardiac Output Syndrome after Pediatric Cardiac Surgery. Curr Vasc Pharmacol. 2016; 14(1):5-13.
  4. Pacak CA, Preble JM, Kondo H, Seibel P, Levitsky S, Del Nido PJ, Cowan DB, McCully JD. Actin-dependent mitochondrial internalization in cardiomyocytes: evidence for rescue of mitochondrial function. Biol Open. 2015; 4(5):622-6.
  5. Pacak CA, Hammer PE, MacKay AA, Dowd RP, Wang KR, Masuzawa A, Sill B, McCully JD, Cowan DB. Superparamagnetic iron oxide nanoparticles function as a long-term, multi-modal imaging label for non-invasive tracking of implanted progenitor cells. PLoS One. 2014; 9(9):e108695.
  6. Preble JM, Pacak CA, Kondo H, MacKay AA, Cowan DB, McCully JD. Rapid isolation and purification of mitochondria for transplantation by tissue dissociation and differential filtration. J Vis Exp. 2014 Sep 06; (91):e51682.
  7. Black KM, Masuzawa A, Hagberg RC, Khabbaz KR, Trovato ME, Rettagliati VM, Bhasin MK, Dillon ST, Libermann TA, Toumpoulis IK, Levitsky S, McCully JD. Preliminary biomarkers for identification of human ascending thoracic aortic aneurysm. J Am Heart Assoc. 2013 Nov 14; 2(6):e000138.
  8. Masuzawa A, Black KM, Pacak CA, Ericsson M, Barnett RJ, Drumm C, Seth P, Bloch DB, Levitsky S, Cowan DB, McCully JD. Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2013 Apr 1; 304(7):H966-82.
  9. Friehs I, Cowan DB, Choi YH, Black KM, Barnett R, Bhasin MK, Daly C, Dillon SJ, Libermann TA, McGowan FX, del Nido PJ, Levitsky S, McCully JD. Pressure-overload hypertrophy of the developing heart reveals activation of divergent gene and protein pathways in the left and right ventricular myocardium. Am J Physiol Heart Circ Physiol. 2013 Mar 1; 304(5):H697-708.
  10. Black KM, Barnett RJ, Bhasin MK, Daly C, Dillon ST, Libermann TA, Levitsky S, McCully JD. Microarray and proteomic analysis of the cardioprotective effects of cold blood cardioplegia in the mature and aged male and female. Physiol Genomics. 2012 Nov 1; 44(21):1027-41.
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  12. Hsieh YJ, Wakiyama H, Levitsky S, McCully JD. Cardioplegia and diazoxide modulate STAT3 activation and DNA binding. Ann Thorac Surg. 2007 Oct; 84(4):1272-8.
  13. McCully JD, Toyoda Y, Wakiyama H, Rousou AJ, Parker RA, Levitsky S. Age- and gender-related differences in ischemia/reperfusion injury and cardioprotection: effects of diazoxide. Ann Thorac Surg. 2006 Jul; 82(1):117-23.
  14. Rousou AJ, Ericsson M, Federman M, Levitsky S, McCully JD. Opening of mitochondrial KATP channels enhances cardioprotection through the modulation of mitochondrial matrix volume, calcium accumulation, and respiration. Am J Physiol Heart Circ Physiol. 2004 Nov; 287(5):H1967-76.
  15. McCully JD, Wakiyama H, Hsieh YJ, Jones M, Levitsky S. Differential contribution of necrosis and apoptosis in myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2004 May; 286(5):H1923-35.
  16. McCully JD, Levitsky S. Mitochondrial ATP-sensitive potassium channels in surgical cardioprotection. Arch Biochem Biophys. 2003 Dec 15; 420(2):237-45.
  17. Levitsky S, Laurikka J, Stewart RD, Campos CT, Lahey SJ, McCully JD. Mitochondrial DNA deletions in coronary artery bypass grafting patients. Eur J Cardiothorac Surg. 2003 Nov; 24(5):777-84.
  18. McCully JD, Levitsky S. The mitochondrial K(ATP) channel and cardioprotection. Ann Thorac Surg. 2003 Feb; 75(2):S667-73.
  19. Bianchi C, Wakiyama H, Faro R, Khan T, McCully JD, Levitsky S, Szabó C, Sellke FW. A novel peroxynitrite decomposer catalyst (FP-15) reduces myocardial infarct size in an in vivo peroxynitrite decomposer and acute ischemia-reperfusion in pigs. Ann Thorac Surg. 2002 Oct; 74(4):1201-7.
  20. McCully JD. Oxygenated multidose delivery of crystalloid esmolol cardioplegia as an alternative to high potassium cardioplegia. J Thorac Cardiovasc Surg. 2002 Aug; 124(2):219-20.
  21. Faro R, Toyoda Y, McCully JD, Jagtap P, Szabo E, Virag L, Bianchi C, Levitsky S, Szabo C, Sellke FW. Myocardial protection by PJ34, a novel potent poly (ADP-ribose) synthetase inhibitor. Ann Thorac Surg. 2002 Feb; 73(2):575-81.
  22. Toyoda Y, Khan S, Chen W, Parker RA, Levitsky S, McCully JD. Effects of NHE-1 inhibition on cardioprotection and impact on protection by K/Mg cardioplegia. Ann Thorac Surg. 2001 Sep; 72(3):836-43; discussion 843-4.
  23. Stadler B, Phillips J, Toyoda Y, Federman M, Levitsky S, McCully JD. Adenosine-enhanced ischemic preconditioning modulates necrosis and apoptosis: effects of stunning and ischemia-reperfusion. Ann Thorac Surg. 2001 Aug; 72(2):555-63; discussion 563-4.
  24. Toyoda Y, Levitsky S, McCully JD. Opening of mitochondrial ATP-sensitive potassium channels enhances cardioplegic protection. Ann Thorac Surg. 2001 Apr; 71(4):1281-8; discussion 1288-9.
  25. Sasaki S, Yasuda K, McCully JD, Palombo JD, LoCicero J. Perfusion with lipopolysaccharide negative blood eliminates lipopolysaccharide induced lung injury. ASAIO J. 2001 Jan-Feb; 47(1):45-9.
  26. Matsuda H, Levitsky S, McCully JD. Inhibition of RNA transcription modulates magnesium-supplemented potassium cardioplegia protection. Ann Thorac Surg. 2000 Dec; 70(6):2107-12.
  27. Toyoda Y, Friehs I, Parker RA, Levitsky S, McCully JD. Differential role of sarcolemmal and mitochondrial K(ATP) channels in adenosine-enhanced ischemic preconditioning. Am J Physiol Heart Circ Physiol. 2000 Dec; 279(6):H2694-703.
  28. Toyoda Y, Di Gregorio V, Parker RA, Levitsky S, McCully JD. Anti-stunning and anti-infarct effects of adenosine-enhanced ischemic preconditioning. Circulation. 2000 Nov 7; 102(19 Suppl 3):III326-31.
  29. McCully JD, Levitsky S. Alternatives for myocardial protection: adenosine-enhanced ischemic preconditioning. Ann N Y Acad Sci. 1999 Jun 30; 874:295-305.
  30. McCully JD, Uematsu M, Levitsky S. Adenosine-enhanced ischemic preconditioning provides myocardial protection equal to that of cold blood cardioplegia. Ann Thorac Surg. 1999 Mar; 67(3):699-704.
  31. Sasaki S, Yasuda K, McCully JD, LoCicero J. Does PGE1 attenuate potassium-induced vasoconstriction in initial pulmonary artery flush on lung preservation? J Heart Lung Transplant. 1999 Feb; 18(2):139-42.
  32. Sasaki S, Yasuda K, McCully JD, LoCicero J. Calcium channel blocker enhances lung preservation. J Heart Lung Transplant. 1999 Feb; 18(2):127-32.
  33. McCully JD, Uematsu M, Parker RA, Levitsky S. Adenosine-enhanced ischemic preconditioning provides enhanced cardioprotection in the aged heart. Ann Thorac Surg. 1998 Dec; 66(6):2037-43.
  34. Uematsu M, Gaudette GR, Laurikka JO, Levitsky S, McCully JD. Adenosine-enhanced ischemic preconditioning decreases infarct in the regional ischemic sheep heart. Ann Thorac Surg. 1998 Aug; 66(2):382-7.
  35. McCully JD, Uematsu M, Parker RA, Levitsky S. Adenosine-enhanced ischemic preconditioning provides enhanced postischemic recovery and limitation of infarct size in the rabbit heart. J Thorac Cardiovasc Surg. 1998 Jul; 116(1):154-62.
  36. Matsuda H, McCully JD, Levitsky S. Developmental differences in cytosolic calcium accumulation associated with global ischemia: evidence for differential intracellular calcium channel receptor activity. Circulation. 1997 Nov 4; 96(9 Suppl):II-233-8; discussion II-238-9.
  37. Tsukube T, McCully JD, Metz KR, Cook CU, Levitsky S. Amelioration of ischemic calcium overload correlates with high-energy phosphates in senescent myocardium. Am J Physiol. 1997 Jul; 273(1 Pt 2):H418-25.
  38. McCully JD, Levitsky S. Mechanisms of in vitro cardioprotective action of magnesium on the aging myocardium. Magnes Res. 1997 Jun; 10(2):157-68.
  39. Krukenkamp IB, McCully J, Levitsky S. "Reperfusion Injury" and Myocardial Protection by Cardioplegia: An Opinion. J Thromb Thrombolysis. 1997 Jan; 4(1):131-132.
  40. McCully JD, Levitsky S. Myocardial protection in the elderly. Biology of the senescent heart. Ann N Y Acad Sci. 1996 Sep 30; 793:305-18.
  41. Tsukube T, McCully JD, Federman M, Krukenkamp IB, Levitsky S. Developmental differences in cytosolic calcium accumulation associated with surgically induced global ischemia: optimization of cardioplegic protection and mechanism of action. J Thorac Cardiovasc Surg. 1996 Jul; 112(1):175-84.
  42. McCully JD, Lotz MM, Krukenkamp IB, Levitsky S. A brief period of retrograde hyperthermic perfusion enhances myocardial protection from global ischemia: association with accumulation of Hsp 70 mRNA and protein. J Mol Cell Cardiol. 1996 Feb; 28(2):231-41.
  43. Sasaki S, Alessandrini F, Lodi R, McCully J, LoCicero J. Improvement of pulmonary graft after storage for twenty-four hours by in vivo administration of lazaroid U74389G: functional and morphologic analysis. J Heart Lung Transplant. 1996 Jan; 15(1 Pt 1):35-42.
  44. Faulk EA, McCully JD, Hadlow NC, Tsukube T, Krukenkamp IB, Federman M, Levitsky S. Magnesium cardioplegia enhances mRNA levels and the maximal velocity of cytochrome oxidase I in the senescent myocardium during global ischemia. Circulation. 1995 Nov 1; 92(9 Suppl):II405-12.
  45. Nanji AA, Griniuviene B, Yacoub LK, Sadrzadeh SM, Levitsky S, McCully JD. Heat-shock gene expression in alcoholic liver disease in the rat is related to the severity of liver injury and lipid peroxidation. Proc Soc Exp Biol Med. 1995 Oct; 210(1):12-9.
  46. Sasaki S, McCully JD, Palombo JD, Forse RA, LoCicero J. Lung preservation threshold in a compromised septic lung injury model. Ann Thorac Surg. 1995 Oct; 60(4):958-62; discussion 962-3.
  47. Faulk EA, McCully JD, Tsukube T, Hadlow NC, Krukenkamp IB, Levitsky S. Myocardial mitochondrial calcium accumulation modulates nuclear calcium accumulation and DNA fragmentation. Ann Thorac Surg. 1995 Aug; 60(2):338-44.
  48. Sasaki S, McCully JD, Alessandrini F, LoCicero J. Impact of initial flush potassium concentration on the adequacy of lung preservation. J Thorac Cardiovasc Surg. 1995 Jun; 109(6):1090-5; discussion 1095-6.
  49. Nanji AA, Griniuviene B, Sadrzadeh SM, Levitsky S, McCully JD. Effect of type of dietary fat and ethanol on antioxidant enzyme mRNA induction in rat liver. J Lipid Res. 1995 Apr; 36(4):736-44.
  50. McCully JD, Myrmel T, Lotz MM, Krukenkamp IB, Levitsky S. The rapid expression of myocardial hsp 70 mRNA and the heat shock 70 kDa protein can be achieved after only a brief period of retrograde hyperthermic perfusion. J Mol Cell Cardiol. 1995 Mar; 27(3):873-82.
  51. Myrmel T, McCully JD, Malikin L, Krukenkamp IB, Levitsky S. Heat-shock protein 70 mRNA is induced by anaerobic metabolism in rat hearts. Circulation. 1994 Nov; 90(5 Pt 2):II299-305.
  52. Tsukube T, McCully JD, Faulk EA, Federman M, LoCicero J, Krukenkamp IB, Levitsky S. Magnesium cardioplegia reduces cytosolic and nuclear calcium and DNA fragmentation in the senescent myocardium. Ann Thorac Surg. 1994 Oct; 58(4):1005-11.
  53. McCully JD, Tsukube T, Ataka K, Krukenkamp IB, Feinberg H, Levitsky S. Myocardial cytosolic calcium accumulation during ischemia/reperfusion: the effects of aging and cardioplegia. J Card Surg. 1994 May; 9(3 Suppl):449-52.
  54. Ataka K, Chen D, McCully J, Levitsky S, Feinberg H. Magnesium cardioplegia prevents accumulation of cytosolic calcium in the ischemic myocardium. J Mol Cell Cardiol. 1993 Dec; 25(12):1387-90.
  55. McCully JD, Wang RX, Kellam B, Sole MJ, Liew CC. Isolation and characterization of a previously unrecognized myosin heavy chain gene present in the Syrian hamster. J Mol Biol. 1991 Apr 20; 218(4):657-65.
  56. McCully JD, Mably JD, Sole MJ, Liew CC. RNA transcription and translation in the hearts of normal and cardiomyopathic Syrian hamsters. Biochem Cell Biol. 1991 Jan; 69(1):88-92.
  57. McCully JD, Liew CC. RNA transcription in myocardial-cell nuclei during postnatal development. A study establishing an assay system for transcription in vitro. Biochem J. 1988 Dec 1; 256(2):441-5.
  58. McCully JD, Jandreski MA, Liew J, Sole MJ, Liew CC. Construction of cosmid genomic libraries for the normal and myopathic Syrian hamsters. Biochem Cell Biol. 1987 Nov; 65(11):997-1000.
  59. McCully JD, Taylor PB, Morrison NL. Alterations in myocardial RNA synthesis and RNA polymerase activity during normal growth. Can J Physiol Pharmacol. 1983 Apr; 61(4):341-8.
  60. McCully JD, Cowan DB, Pacak CA, Toumpoulis IK, Dayalan H, Levitsky S. Injection of isolated mitochondria during early reperfusion for cardioprotection. Am J Physiol Heart Circ Physiol. 2009 Jan; 296(1):H94-H105.
  61. Toumpoulis IK, Oxford JT, Cowan DB, Anagnostopoulos CE, Rokkas CK, Chamogeorgakis TP, Angouras DC, Shemin RJ, Navab M, Ericsson M, Federman M, Levitsky S, McCully JD. Differential expression of collagen type V and XI alpha-1 in human ascending thoracic aortic aneurysms. Ann Thorac Surg. 2009 Aug; 88(2):506-13.
  62. Tansey EE, Kwaku KF, Hammer PE, Cowan DB, Federman M, Levitsky S, McCully JD. Reduction and redistribution of gap and adherens junction proteins after ischemia and reperfusion. Ann Thorac Surg. 2006 Oct; 82(4):1472-9.
  63. McCully JD, Rousou AJ, Parker RA, Levitsky S. Age- and gender-related differences in mitochondrial oxygen consumption and calcium with cardioplegia and diazoxide. Ann Thorac Surg. 2007 Mar; 83(3):1102-9.
  64. McCully JD, Wakiyama H, Cowan DB, Federman M, Parker RA, Levitsky S. Diazoxide amelioration of myocardial injury and mitochondrial damage during cardiac surgery. Ann Thorac Surg. 2002 Dec; 74(6):2138-45; discussion 2146.
  65. Wakiyama H, Cowan DB, Toyoda Y, Federman M, Levitsky S, McCully JD. Selective opening of mitochondrial ATP-sensitive potassium channels during surgically induced myocardial ischemia decreases necrosis and apoptosis. Eur J Cardiothorac Surg. 2002 Mar; 21(3):424-33.
  66. McCully JD, Bhasin MK, Daly C, Guerrero MC, Dillon S, Liberman TA, Cowan DB, Mably JD, McGowan FX, Levitsky S. Transcriptomic and proteomic analysis of global ischemia and cardioprotection in the rabbit heart. Physiol Genomics. 2009 Jul 9; 38(2):125-37.
  67. McCully JD, Toyoda Y, Uematsu M, Stewart RD, Levitsky S. Adenosine-enhanced ischemic preconditioning: adenosine receptor involvement during ischemia and reperfusion. Am J Physiol Heart Circ Physiol. 2001 Feb; 280(2):H591-602.
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