Wei Dong Gao, MD

Primary Academic Title

Associate Professor of Anesthesiology and Critical Care Medicine

Background

CV

http://www.hopkinsmedicine.org/anesthesiology/faculty/cv/gao.pdf

Research Interests

Cardiac Muscle Physiology, Excitation-contraction Coupling in Ischemia/reperfusion and Heart Failure, Oxidative Stress in Heart Failure

Lab Website

Wei Dong Gao Lab - Lab Website

Research Summary

The main goal of Dr. Gao’s research is to define the molecular and cellular mechanisms of contractile dysfunction in the failing heart. To work toward this goal, he uses a variety of state-of-the-art techniques. Using the fluorescent dye fura-2 salt, he measures the intracellular free calcium concentration in multicellular cardiac tissue preparations called trabeculae. In the same preparations, he measures sarcomere length (using a laser diffraction technique) and force development simultaneously. In addition, he uses molecular biology and proteomic techniques to investigate the changes that myofilament proteins undergo during heart failure and under drug therapy. Dr. Gao’s current focus is determining the molecular nature of nitroxyl (HNO) modification of tropomyosin. He is also planning to study the physiology and biochemistry of atrial tissue and muscle during atrial fibrillation or atrial failure and the effect of atrial dysfunction on the development and progress of heart failure. In the future, he hopes to characterize endo-myocardio-coupling in the failing heart. He would like to investigate the role of endothelial endocardium, the role of coronary endocardium and the effects of agents released from endothelial cells.

Selected Publications

• A. Selected Peer-reviewed articles

  1. Backx, P.H., Gao, W.D., Azan-Backx, M.D., Marban, E. Mechanism of force inhibition by 2,3-butanedione monoxiime in rat cardiac muscle: role of intracellular calcium and cross-bridge Kinetics. J Physiol. 476:487-500, 1994).
  2. Gao, W.D., Backx, P.H., Azan-Backx, M.D., Marban, E. Myofilament Ca2+ sensitivity in intact versus skinned rat ventricular muscle. Circ Res. 74;408-415, 1994.
  3. Backx, P.H., Gao, W.D., Azan-Backx, M.D., Marban, E. The relationship between contractile force and intracellular [Ca2+]i in intact rat cardiac trabeculae. J Gen Physiol. 105:1-19, 1995.
  4. Gao, W.D., Atar, A., Backx, P.H., Marban, E. Relationship between intracellular calcium and contractile force in stunned myocardium: Direct evidence for decreases myofilament Ca2+ responsiveness and altered diastolic function in intact ventricular muscle. Circ Res. 76:1036-1048, 1995
  5. Gao, W.D., Liu, Y., Mellgren, R., Marban, E. Intrinsic myofilaments alterations underlying the decreased contractility of stunned myocardium: A consequence of calcium-dependent proteolysis? Circ Res. 78:455-465, 1996.
  6. Liu, Y., Gao, W.D., O''Rourke, B., Marban, E. Synergistic potentiation of ATP-sensitive potassium currents by protein kinase C and adenosine: Implications for ischemic preconditioning. Circ Res. 78:443-454, 1996.
  7. Gao, W.D., Liu, Y., Marban, E. Selective effects of oxygen free radicals on excitation-contraction coupling in ventricular muscle: Implications for the mechanism of stunned myocardium. Circulation 94:2597-2604, 1996.
  8. Gao, W.D., Atar, D., Liu, Y., Perez, N.G., Murphy, A.M., Marban, E. Role of troponin I proteolysis in the pathogenesis of myocardial stunning. Circ Res. 80:393-399, 1997.
  9. Gao, W.D., Perez, N.G., Marban,E. Calcium cycling and contractile activation in intact mouse cardiac muscle. J Physiol. 507:175-184, 1998.
  10. Perez, N.G., Gao, W.D., Marban, E. Novel myofilament calcium-sensitizing property of xanthine oxidase inhibitors. Circ Res. 83:423-430, 1998.
  11. Gao, W.D., Perez, N.P., Seidman, C., Seidman, J., Marban, E. Altered cardiac excitation-contraction coupling in cardiac muscle from mutant mice with familial hypertrophic cardiomyopathy. J Clin Invest. 103:661-666, 1999.
  12. Stull, L.B., Leppo, M.K., Szweda, L., Gao, W.D., Marban, E. Chronic treatment with allopurinol boosts survival and cardiac contractility in murine postischemic cardiomyopathy. Circ Res. 95:1005-1011, 2004.
  13. Gao, W.D., Dai, T., Nyhan, D. Increased cross-bridge cycling rate in stunned myocardium. Am J Physiol. 290:H886-H893, 2006. 
  14. Dai, T., Ramirez-Correa, G., Gao, W.D. Apelin increases contractility in failing cardiac muscle. Eur J Pharma. 553:222-228, 2006)
  15. Bilchick, K., Duncan, J.G., Ravi, R., Takimoto, E., Champion, H.C., Gao, W.D., Stull, L.S., Kass, D.A., Murphy, A.M. Heart failure-associated alterations in troponin I phosphorylation impair left ventricular relaxation response to afterload, force-frequency response and systolic function. Am J Physiol. 292:H318-325, 2007.
  16. Tocchetti, C.G., Wang, W., Froehlich, J.P., Valdivia, H.H., Pavlos, C.M., Aon, M., Wilson, G.M., di Benedetto, G., O Rourke, B., Miranda, K.M., Mancardi, D., Wink, D.A., Zaccolo, M., Toscano, J.P., Cheng, H., Gao, W.D., Kass, D.A., Paolocci, N. Nitroxyl (HNO) enhances sarcoplasmic reticulum Ca2+ cycling to increase cardiac contractility and relaxation Circ Res 100:96-104, 2007.
  17. Dai, T., Tian, Y., Tocchetti, C.G., Katori, T.A., Kass, D.A., Paolocci, N., Gao, W.D. Nitroxyl anion (HNO/NO-) increases myofilament Ca2+ responsiveness in rat cardiac muscle. J Physiol. 580:951-960, 2007. (accompanying perspective by RJ Solaro: 580:697)
  18. Gao WD, Muphy AM. “Local control in thin filament activation of cardiac muscle.” J Physiol 580(Pt. 2):358, 2007.
  19. Jin, W., Z. Zhao, G.A. Ramirez-Correa, X. Zhong, W.D.Gao, G.W. Hart, A.M. Murphy. O-linked GlcNac Modification of Cardiac Myocardial Contractile Function. Circ Res. 103(12):1354-8, 2008
  20. Tan Z, Dai T, Zhong X, Tian Y, Leppo MK, Gao WD. “Preservation of cardiac contractility after long-term therapy with oxypurinol in post-ischemic heart failure in mice.” Eur J Pharmacol 621:71–7, 2009.
  21. Kohr MJ, Kaludercic N, Tocchetti CG, Gao WD, Kass DA, Janssen PML, Paolocci N, Ziolo MT. “Nitroxyl enhances myocyte Ca2+ transients by exclusively targeting Ca2+-cycling.” Front Biosci (Elite Ed) 2:614–26, 2010.
  22. Ramirez-Correa GA, Cortassa S, Stanley B, Gao WD, Murphy AM. “Calcium sensitivity, force frequency relationship and cardiac troponin I: Critical role of PKA and PKC phosphorylation sites.” J Mol Cell Cardiol 48:943–53, 2010.
  23. Tocchetti CG, Stanley BA, Murray CI, Sivakumaran V, Donzelli S, Mancardi D, Pagliaro P, Gao WD, van Eyk J, Kass DA, Wink DA, Paolocci N. “Playing with cardiac ‘redox switches’: the ‘HNO way’ to modulate cardiac function.” Antioxid Redox Signal. 2011 May 1;14(9):1687-98. doi: 10.1089/ars.2010.3859. Epub 2011 Mar 3. Review.
  24. Ding W, Li Z, Shen X, Martin J, King SB, Sivakumaran V, Paolocci N, Gao WD. “Reversal of isoflurane-induced depression of myocardial contraction by nitroxyl via myofilament sensitization to Ca2+.” J Pharmacol Exp Ther. 2011 Dec;339(3):825-31. doi: 10.1124/jpet.111.185272. Epub 2011 Aug 24.
  25. Sheinberg R, Gao WD, Wand G, Abraham S, Schulick R, Roy R, Mitter N. “Case 1-2012 a perfect storm: fatality resulting from metoclopramide unmasking a pheochromocytoma and its management.” J Cardiothorac Vasc Anesth 26(1):161–5, 2012.
  26. Gao WD, Murray CI, Tian Y, Zhong X, DuMond JF, Shen X, Stanley BA, Foster DB, Wink DA, King SB, Van Eyk JE, Paolocci N. “Nitroxyl-mediated disulfide bond formation between cardiac myofilament cysteines enhances contractile function.” Circ Res 111(8):1002–11, 2012.
  27. Shen X, Tan Z, Zhong X, Tian Y, Wang X, Yu B, Ramirez-Correa G, Murphy A, Gabrielson K, Paolocci N, Gao WD. “Endocardial endothelium is a key determinant of force-frequency relationship in rat ventricular myocardium.” J Appl Physiol (1985). 2013 Aug 1;115(3):383-93. doi: 10.1152/japplphysiol.01415.2012. Epub 2013 May 23.

  
  B. Selected book chapters and reviews
  
  

  1. Marban, E., Gao, W.D. Stunned myocardium: a disease of the myofilaments? Basic Res Cardiol. 90:269-272, 1995.
  2. Liu, Y., Gao, W.D., ORourke, B., Marban, E. Protein kinase C and adenosine synergistically activate ATP-sensitive potassium currents: Implications for ischemic preconditioning. In Adenosine, cardioprotection and clinical application. Eds: R.M. Mentzer, Jr, M. Kitakaze, J.M. Downey, M. Hori. Kluwer Academic Publishers, Boston, pp153-166,1997.
  3. Gao, W.D., Marban, E. Myocardial stunning and preconditioning: clinical implications. In Perioperative Care of Cardiopulmonary Comprised Patients. Eds L Flesher and DS Prough, 13(2):pp172-180, 2001.
  4. Gao, W.D., Murphy, A. Local Control in Thin Filament Activation of Cardiac Muscle. (Perspective) J Physiol. 580:358, 2007.

Honors

• Clinician-Scientist Award, The Johns Hopkins University School of Medicine, 1/1/02
• International Research Fellowship, American Heart Association, 1/1/92
• William H. Davis Scholarship for Medical Research, University of Calgary, 1/1/87
• Triple-Excellency Student Award, Harbin Medical University, 1/1/82

Lectures & Presentations

Heart Failure: Mechanisms, Augmenting Contractility and Anesthesia Considerations, http://webcast.jhu.edu/Mediasite/Play/0cc104bff44d413783c45fd36b9041521d, 9/8/11

Memberships

• American Society of Anesthesiology
• Association of University Anesthesiologists (AUA)
• Maryland Society of Anesthesiologists

Professional Activities

• American Journal of Physiology (Heart & Circulation), Peer reviewer, 1/1/03
• Anesthesia & Analgesia, Peer reviewer, 1/1/06
• Anesthesiology, Peer reviewer, 1/1/95 - 1/1/02
• Cardiovascular Research, Peer reviewer, 1/1/93
• Circulation, Peer reviewer, 1/1/94
• Circulation Research, Peer reviewer, 1/1/94
• Journal of Applied Physiology, Peer reviewer, 1/1/06
• Journal of European Pharmacology, Peer reviewer, 1/1/06
• Journal of Molecular and Cellular Cardiology, Peer reviewer, 1/1/94
• Regulatory Peptides, Peer reviewer, 1/1/06
• The Journal of Physiology, Peer reviewer, 1/1/06