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. Emani SM, McCully JD. Mitochondrial transplantation: applications for pediatric patients with congenital heart disease. Transl Pediatr. 2018 Apr; 7(2):169-175. View abstract
  2. Ramirez-Barbieri G, Moskowitzova K, Shin B, Blitzer D, Orfany A, Guariento A, Iken K, Friehs I, Zurakowski D, Del Nido PJ, McCully JD. Alloreactivity and allorecognition of syngeneic and allogeneic mitochondria. Mitochondrion. 2018 Mar 26. View abstract
  3. Cowan DB, Yao R, Thedsanamoorthy JK, Zurakowski D, Del Nido PJ, McCully JD. Transit and integration of extracellular mitochondria in human heart cells. Sci Rep. 2017 Dec 12; 7(1):17450. View abstract
  4. McCully JD. Invited Commentary. Ann Thorac Surg. 2017 10; 104(4):1304-1305. View abstract
  5. McCully JD, Cowan DB, Emani SM, Del Nido PJ. Mitochondrial transplantation: From animal models to clinical use in humans. Mitochondrion. 2017 05; 34:127-134. View abstract
  6. Emani SM, Piekarski BL, Harrild D, Del Nido PJ, McCully JD. Autologous mitochondrial transplantation for dysfunction after ischemia-reperfusion injury. J Thorac Cardiovasc Surg. 2017 Jul; 154(1):286-289. View abstract
  7. Shin B, Cowan DB, Emani SM, Del Nido PJ, McCully JD. Mitochondrial Transplantation in Myocardial Ischemia and Reperfusion Injury. Adv Exp Med Biol. 2017; 982:595-619. View abstract
  8. Kaza AK, Wamala I, Friehs I, Kuebler JD, Rathod RH, Berra I, Ericsson M, Yao R, Thedsanamoorthy JK, Zurakowski D, Levitsky S, Del Nido PJ, Cowan DB, McCully JD. Myocardial rescue with autologous mitochondrial transplantation in a porcine model of ischemia/reperfusion. J Thorac Cardiovasc Surg. 2017 Apr; 153(4):934-943. View abstract
  9. 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. View abstract
  10. McCully JD, Levitsky S, Del Nido PJ, Cowan DB. Mitochondrial transplantation for therapeutic use. Clin Transl Med. 2016 Mar; 5(1):16. View abstract
  11. 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. View abstract
  12. 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 Apr 10; 4(5):622-6. View abstract
  13. 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. View abstract
  14. 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. View abstract
  15. 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. View abstract
  16. 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 01; 304(7):H966-82. View abstract
  17. 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 01; 304(5):H697-708. View abstract
  18. 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 01; 44(21):1027-41. View abstract
  19. 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. View abstract
  20. 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 09; 38(2):125-37. View abstract
  21. 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. View abstract
  22. 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. View abstract
  23. 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. View abstract
  24. 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. View abstract
  25. 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. View abstract
  26. 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. View abstract
  27. 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. View abstract
  28. McCully JD, Levitsky S. Mitochondrial ATP-sensitive potassium channels in surgical cardioprotection. Arch Biochem Biophys. 2003 Dec 15; 420(2):237-45. View abstract
  29. 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. View abstract
  30. McCully JD, Levitsky S. The mitochondrial K(ATP) channel and cardioprotection. Ann Thorac Surg. 2003 Feb; 75(2):S667-73. View abstract
  31. 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. View abstract
  32. 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. View abstract
  33. 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. View abstract
  34. 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. View abstract
  35. 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. View abstract
  36. 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. View abstract
  37. 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. View abstract
  38. 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. View abstract
  39. 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. View abstract
  40. 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. View abstract
  41. 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. View abstract
  42. 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. View abstract
  43. 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 07; 102(19 Suppl 3):III326-31. View abstract
  44. McCully JD, Levitsky S. Alternatives for myocardial protection: adenosine-enhanced ischemic preconditioning. Ann N Y Acad Sci. 1999 Jun 30; 874:295-305. View abstract
  45. 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. View abstract
  46. 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. View abstract
  47. Sasaki S, Yasuda K, McCully JD, LoCicero J. Calcium channel blocker enhances lung preservation. J Heart Lung Transplant. 1999 Feb; 18(2):127-32. View abstract
  48. 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. View abstract
  49. 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. View abstract
  50. 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. View abstract
  51. 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 04; 96(9 Suppl):II-233-8; discussion II-238-9. View abstract
  52. 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. View abstract
  53. McCully JD, Levitsky S. Mechanisms of in vitro cardioprotective action of magnesium on the aging myocardium. Magnes Res. 1997 Jun; 10(2):157-68. View abstract
  54. Krukenkamp IB, McCully J, Levitsky S. "Reperfusion Injury" and Myocardial Protection by Cardioplegia: An Opinion. J Thromb Thrombolysis. 1997 Jan; 4(1):131-132. View abstract
  55. 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. View abstract
  56. 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. View abstract
  57. 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. View abstract
  58. 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. View abstract
  59. 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 01; 92(9 Suppl):II405-12. View abstract
  60. 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. View abstract
  61. 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. View abstract
  62. 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. View abstract
  63. 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. View abstract
  64. 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. View abstract
  65. 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. View abstract
  66. 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. View abstract
  67. 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. View abstract
  68. 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. View abstract
  69. 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. View abstract
  70. 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. View abstract
  71. 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. View abstract
  72. 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 01; 256(2):441-5. View abstract
  73. 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. View abstract
  74. 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. View abstract