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Douglas  Cowan, PhD

Douglas Cowan
Lab:
Cowan Laboratory
Department:
Department of Anesthesiology, Perioperative and Pain Medicine Research
Division
Cardiac Anesthesia Research
Hospital Title:
Research Associate
Academic Title:
Associate Professor, Harvard Medical School
Research Focus Area:
Heart DiseaseStem Cell BiologyTissue EngineeringMolecular Imaging
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Research Overview

Our laboratory studies the cardiovascular system with a specific focus on combining tissue engineering and stem cell biology to improve heart function in various patient populations. Current projects in our laboratory include the following:

  • Cardiac Conduction through Engineered Tissue – We are engineering tissues to act as electrical conduits for use in pediatric patients with complete heart block. Ultimately, we hope to provide a realistic alternative or accessory treatment to conventional cardiac pacemaker implantation in children.
  • Adult Stem Cell Culture – We are developing methods to expand and control the fate of tissue-specific stem cells to determine their regenerative potential for the treatment of cardiac and skeletal muscle disorders. Our studies are designed to advance cell-based therapies for a variety of human diseases.
  • Non-invasive Tracking of Transplanted Cells – We are assessing non-invasive imaging methods to serially track the retention, distribution, and function of transplanted cells in the heart. We believe these methods will have immediate relevance for assessing the efficacy of cardiac cell-based therapies.
  • Mitochondrial Transplantation – This collaborative project is focused on providing a clinically-relevant treatment for myocardial infarction in adults. We and our colleagues are injecting autologous mitochondria into the heart to decrease the extent of damage and enhance functional recovery.

About Douglas B. Cowan

Douglas Cowan received his PhD from the University of Toronto in 1994. He was a Fellow of the Medical Research Council of Canada at the Samuel Lunenfeld Research Institute at Mount Sinai Hospital before moving to Children's Hospital Boston in 1998. Dr Cowan is the recipient of several awards and honors including the Stuart Alan Hoffman Award for Research Excellence and one of the 2012 AND 2013 FASEB BioArt Awards.

Publications

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  1. 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. 2016; (in press).
  2. 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.
  3. McCully JD, Levitsky S, Del Nido PJ, Cowan DB. Mitochondrial transplantation for therapeutic use. Clin Transl Med. 2016 Mar; 5(1):16.
  4. Neef K, Treskes P, Xu G, Drey F, Srinivasan SP, Saric T, Nembo E, Semmler J, Nguemo F, Stamm C, Cowan DB, Deppe AC, Scherner M, Wittwer T, Hescheler J, Wahlers T, Choi YH. Dynamic Support Culture of Murine Skeletal Muscle-Derived Stem Cells Improves Their Cardiogenic Potential In Vitro. Stem Cells Int. 2015; 2015:247091.
  5. 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.
  6. 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.
  7. Treskes P, Neef K, Perumal Srinivasan S, Halbach M, Stamm C, Cowan D, Scherner M, Madershahian N, Wittwer T, Hescheler J, Wahlers T, Choi YH. Preconditioning of skeletal myoblast-based engineered tissue constructs enables functional coupling to myocardium in vivo. J Thorac Cardiovasc Surg. 2015 Jan; 149(1):348-56.
  8. 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.
  9. Pacak CA, MacKay AA, Cowan DB. An improved method for the preparation of type I collagen from skin. J Vis Exp. 2014 Jan 21; (83):e51011.
  10. Pacak CA, Cowan DB. Growth of bone marrow and skeletal muscle side population stem cells in suspension culture. Methods Mol Biol. 2014; 1210:51-61.
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  12. 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.
  13. 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.
  14. Neef K, Choi YH, Perumal Srinivasan S, Treskes P, Cowan DB, Stamm C, Rubach M, Adelmann R, Wittwer T, Wahlers T. Mechanical preconditioning enables electrophysiologic coupling of skeletal myoblast cells to myocardium. J Thorac Cardiovasc Surg. 2012 Nov; 144(5):1176-1184.e1.
  15. Perumal Srinivasan S, Neef K, Treskes P, Liakopoulos OJ, Stamm C, Cowan DB, Madershahian N, Kuhn E, Slottosch I, Wittwer T, Wahlers T, Choi YH. Enhanced gap junction expression in myoblast-containing engineered tissue. Biochem Biophys Res Commun. 2012 Jun 8; 422(3):462-8.
  16. Pacak CA, Powers JM, Cowan DB. Ultrarapid purification of collagen type I for tissue engineering applications. Tissue Eng Part C Methods. 2011 Sep; 17(9):879-85.
  17. Luxameechanporn T, Hadlock T, Shyu J, Cowan D, Faquin W, Varvares M. Successful myoblast transplantation in rat tongue reconstruction. Head Neck. 2006 Jun; 28(6):517-24.
  18. Bunaprasert T, Hadlock T, Marler J, Kobler J, Cowan D, Faquin W, Varvares M. Tissue engineered muscle implantation for tongue reconstruction: a preliminary report. Laryngoscope. 2003 Oct; 113(10):1792-7.
  19. Soriano SG, Cowan DB, Proctor MR, Scott RM. Levels of soluble adhesion molecules are elevated in the cerebrospinal fluid of children with moyamoya syndrome. Neurosurgery. 2002 Mar; 50(3):544-9.
  20. Stamm C, Cowan DB, Friehs I, Noria S, del Nido PJ, McGowan FX. Rapid endotoxin-induced alterations in myocardial calcium handling: obligatory role of cardiac TNF-alpha. Anesthesiology. 2001 Dec; 95(6):1396-405.
  21. Stamm C, Friehs I, Cowan DB, Moran AM, Cao-Danh H, Duebener LF, del Nido PJ, McGowan FX. Inhibition of tumor necrosis factor-alpha improves postischemic recovery of hypertrophied hearts. Circulation. 2001 Sep 18; 104(12 Suppl 1):I350-5.
  22. Cowan DB, Noria S, Stamm C, Garcia LM, Poutias DN, del Nido PJ, McGowan FX. Lipopolysaccharide internalization activates endotoxin-dependent signal transduction in cardiomyocytes. Circ Res. 2001 Mar 16; 88(5):491-8.
  23. MacGowan GA, Du C, Cowan DB, Stamm C, McGowan FX, Solaro RJ, Koretsky AP, Del Nido PJ. Ischemic dysfunction in transgenic mice expressing troponin I lacking protein kinase C phosphorylation sites. Am J Physiol Heart Circ Physiol. 2001 Feb; 280(2):H835-43.
  24. Takeuchi K, del Nido PJ, Poutias DN, Cowan DB, Munakata M, McGowan FX. Vesnarinone restores contractility and calcium handling in early endotoxemia. Circulation. 2000 Nov 7; 102(19 Suppl 3):III365-9.
  25. Cowan DB, Poutias DN, Del Nido PJ, McGowan FX. CD14-independent activation of cardiomyocyte signal transduction by bacterial endotoxin. Am J Physiol Heart Circ Physiol. 2000 Aug; 279(2):H619-29.
  26. Noria S, Cowan DB, Gotlieb AI, Langille BL. Transient and steady-state effects of shear stress on endothelial cell adherens junctions. Circ Res. 1999 Sep 17; 85(6):504-14.
  27. Takeuchi K, del Nido PJ, Ibrahim AE, Poutias DN, Glynn P, Cao-Danh H, Cowan DB, McGowan FX. Increased myocardial calcium cycling and reduced myofilament calcium sensitivity in early endotoxemia. Surgery. 1999 Aug; 126(2):231-8.
  28. Takeuchi K, del Nido PJ, Ibrahim AE, Cao-Danh H, Friehs I, Glynn P, Poutias D, Cowan DB, McGowan FX. Vesnarinone and amrinone reduce the systemic inflammatory response syndrome. J Thorac Cardiovasc Surg. 1999 Feb; 117(2):375-82.
  29. Cowan DB, Lye SJ, Langille BL. Regulation of vascular connexin43 gene expression by mechanical loads. Circ Res. 1998 Apr 20; 82(7):786-93.
  30. Cowan DB, Langille BL. Cellular and molecular biology of vascular remodeling. Curr Opin Lipidol. 1996 Apr; 7(2):94-100.
  31. Li RK, Cowan DB, Mickle DA, Weisel RD, Burton GW. Effect of vitamin E on human glutathione peroxidase (GSH-PX1) expression in cardiomyocytes. Free Radic Biol Med. 1996; 21(4):419-26.
  32. Cowan DB, Weisel RD, Williams WG, Mickle DA. Identification of oxygen responsive elements in the 5'-flanking region of the human glutathione peroxidase gene. J Biol Chem. 1993 Dec 25; 268(36):26904-10.
  33. Cowan DB, Weisel RD, Williams WG, Mickle DA. The regulation of glutathione peroxidase gene expression by oxygen tension in cultured human cardiomyocytes. J Mol Cell Cardiol. 1992 Apr; 24(4):423-33.
  34. Cowan DB, Chaban G, Liew CC. The DNA-binding properties of a rat nuclear phosphoprotein. Biochem J. 1991 Mar 15; 274 ( Pt 3):687-91.
  35. Chanani NK, Cowan DB, Takeuchi K, Poutias DN, Garcia LM, del Nido PJ, McGowan FX. Differential effects of amrinone and milrinone upon myocardial inflammatory signaling. Circulation. 2002 Sep 24; 106(12 Suppl 1):I284-9.
  36. Chen JN, Cowan DB, Mably JD. Cardiogenesis and the regulation of cardiac-specific gene expression. Heart Fail Clin. 2005 Jul; 1(2):157-70.
  37. Sill B, Hammer PE, Cowan DB. Optical mapping of Langendorff-perfused rat hearts. J Vis Exp. 2009 Aug 11; (30).
  38. Pacak CA, Eddy MT, Woodhull L, Wang KR, Alpatov I, Fullen S, Dowd RP, Choi YH, Cowan DB. Microcarrier-based expansion of adult murine side population stem cells. PLoS One. 2013; 8(1):e55187.
  39. Choi YH, Stamm C, Hammer PE, Kwaku KF, Marler JJ, Friehs I, Jones M, Rader CM, Roy N, Eddy MT, Triedman JK, Walsh EP, McGowan FX, del Nido PJ, Cowan DB. Cardiac conduction through engineered tissue. Am J Pathol. 2006 Jul; 169(1):72-85.
  40. Cowan DB, McGowan FX. A paradigm shift in cardiac pacing therapy? Circulation. 2006 Sep 5; 114(10):986-8.
  41. Wolf CM, Seslar SP, den Boer K, Juraszek AL, McGowan FX, Cowan DB, Del Nido P, Triedman JK, Berul CI, Walsh EP. Atrial remodeling after the Fontan operation. Am J Cardiol. 2009 Dec 15; 104(12):1737-42.
  42. 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.
  43. Choi YH, Cowan DB, Moran AM, Colan SD, Stamm C, Takeuchi K, Friehs I, del Nido PJ, McGowan FX. Myocyte apoptosis occurs early during the development of pressure-overload hypertrophy in infant myocardium. J Thorac Cardiovasc Surg. 2009 Jun; 137(6):1356-62, 1362.e1-3.
  44. Choi YH, Cowan DB, Wahlers TC, Hetzer R, Del Nido PJ, Stamm C. Calcium sensitisation impairs diastolic relaxation in post-ischaemic myocardium: implications for the use of Ca(2+) sensitising inotropes after cardiac surgery. Eur J Cardiothorac Surg. 2010 Feb; 37(2):376-83.
  45. 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.
  46. 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.
  47. Nathan M, Friehs I, Choi YH, Cowan DB, Cao-Danh H, McGowan FX, del Nido PJ. Cyclosporin A but not FK-506 protects against dopamine-induced apoptosis in the stunned heart. Ann Thorac Surg. 2005 May; 79(5):1620-6.
  48. Stamm C, Friehs I, Cowan DB, Cao-Danh H, Noria S, Munakata M, McGowan FX, del Nido PJ. Post-ischemic PKC inhibition impairs myocardial calcium handling and increases contractile protein calcium sensitivity. Cardiovasc Res. 2001 Jul; 51(1):108-21.
  49. Pacak CA, Cowan DB. Fabrication of myogenic engineered tissue constructs. J Vis Exp. 2009 May 01; (27).
  50. Kitahori K, He H, Kawata M, Cowan DB, Friehs I, Del Nido PJ, McGowan FX. Development of left ventricular diastolic dysfunction with preservation of ejection fraction during progression of infant right ventricular hypertrophy. Circ Heart Fail. 2009 Nov; 2(6):599-607.
  51. 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.
  52. Choi YH, Cowan DB, Nathan M, Poutias D, Stamm C, del Nido PJ, McGowan FX. Myocardial hypertrophy overrides the angiogenic response to hypoxia. PLoS One. 2008; 3(12):e4042.
  53. Stamm C, Cowan DB. Endotoxemia and cardiac function. J Thorac Cardiovasc Surg. 2004 Jan; 127(1):305.
  54. Merante F, Altamentova SM, Mickle DA, Weisel RD, Thatcher BJ, Martin BM, Marshall JG, Tumiati LC, Cowan DB, Li RK. The characterization and purification of a human transcription factor modulating the glutathione peroxidase gene in response to oxygen tension. Mol Cell Biochem. 2002 Jan; 229(1-2):73-83.
  55. Munakata M, Stamm C, Friehs I, Zurakowski D, Cowan DB, Cao-Danh H, McGowan FX, del Nido PJ. Protective effects of protein kinase C during myocardial ischemia require activation of phosphatidyl-inositol specific phospholipase C. Ann Thorac Surg. 2002 Apr; 73(4):1236-45.
  56. Bayliss PE, Bellavance KL, Whitehead GG, Abrams JM, Aegerter S, Robbins HS, Cowan DB, Keating MT, O'Reilly T, Wood JM, Roberts TM, Chan J. Chemical modulation of receptor signaling inhibits regenerative angiogenesis in adult zebrafish. Nat Chem Biol. 2006 May; 2(5):265-73.
  57. Friehs I, Cao-Danh H, Stamm C, Cowan DB, McGowan FX, del Nido PJ. Postnatal increase in insulin-sensitive glucose transporter expression is associated with improved recovery of postischemic myocardial function. J Thorac Cardiovasc Surg. 2003 Jul; 126(1):263-71.
  58. Stamm C, Friehs I, Cowan DB, Cao-Danh H, Choi YH, Duebener LF, McGowan FX, del Nido PJ. Dopamine treatment of postischemic contractile dysfunction rapidly induces calcium-dependent pro-apoptotic signaling. Circulation. 2002 Sep 24; 106(12 Suppl 1):I290-8.
  59. 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.
  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. Sill B, Alpatov IV, Pacak CA, Cowan DB. Implantation of engineered tissue in the rat heart. J Vis Exp. 2009 Jun 24; (28).
  62. Sill B, Roy N, Hammer PE, Triedman JK, Sigg DC, Kelly MF, Nedder A, Dunning PS, Cowan DB. Development of an ovine model of pediatric complete heart block. J Surg Res. 2011 Apr; 166(2):e103-8.
  63. Yoon S, Molloy MJ, Wu MP, Cowan DB, Gussoni E. C6ORF32 is upregulated during muscle cell differentiation and induces the formation of cellular filopodia. Dev Biol. 2007 Jan 1; 301(1):70-81.
  64. Roy N, Friehs I, Cowan DB, Zurakowski D, McGowan FX, del Nido PJ. Dopamine induces postischemic cardiomyocyte apoptosis in vivo: an effect ameliorated by propofol. Ann Thorac Surg. 2006 Dec; 82(6):2192-9.
  65. Friehs I, Moran AM, Stamm C, Choi YH, Cowan DB, McGowan FX, del Nido PJ. Promoting angiogenesis protects severely hypertrophied hearts from ischemic injury. Ann Thorac Surg. 2004 Jun; 77(6):2004-10; discussion 2011.
  66. Cowan DB, Jones M, Garcia LM, Noria S, del Nido PJ, McGowan FX. Hypoxia and stretch regulate intercellular communication in vascular smooth muscle cells through reactive oxygen species formation. Arterioscler Thromb Vasc Biol. 2003 Oct 1; 23(10):1754-60.
  67. Bartholomä MD, He H, Pacak CA, Dunning P, Fahey FH, McGowan FX, Cowan DB, Treves ST, Packard AB. Biological characterization of F-18-labeled rhodamine B, a potential positron emission tomography perfusion tracer. Nucl Med Biol. 2013 Nov; 40(8):1043-8.
  68. Bartholomä MD, Zhang S, Akurathi V, Pacak CA, Dunning P, Fahey FH, Cowan DB, Treves ST, Packard AB. (18)F-labeled rhodamines as potential myocardial perfusion agents: comparison of pharmacokinetic properties of several rhodamines. Nucl Med Biol. 2015 Oct; 42(10):796-803.
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