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Department of Anesthesiology/Critical Care Medicine
The Johns Hopkins University School of Medicine
Sheikh Zayed Tower 6208
1800 Orleans Street
Baltimore, MD 21287
The main goal of Dr. Wei Dong Gao’s research is to define the molecular and cellular mechanisms of contractile dysfunction in the failing heart. To work toward this goal, he is using a variety of state-of-the-art techniques. Using the fluorescent dye fura-2 salt, he measures the intracellular free calcium concentration in a 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 and/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 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.
Journal peer reviewer
American Journal of Physiology (Heart & Circulaltion); Anesthesia & Analgesia; Anesthesiology; Cardiovascular Research, Circulation; Circulation Research; Journal of Applied Physiology; Journal of European Pharmacology; Journal of Molecular and Cellular Cardiology; The Journal of Physiology; Regulatory Peptides
- Gao WD, Dai T, Nyhan D. Increased cross-bridge cycling rate in stunned mocardium. Am J Physiol 290:H886–93, 2006.
- Dai T, Ramirez-Correa G, Gao WD. Apelin increases contractility in failing cardiac muscle. Br J Pharmacol 553:222–8, 2006.
- Tocchetti CG, Wang W, Froehlich JP, Huke S, Aon MA, Wilson GM, Di Benedetto G, O'Rourke B, Gao WD, Wink DA, Toscano JP, Zaccolo M, Bers DM, Valdivia HH, Cheng H, Kass DA, Paolocci N. Nitroxyl improves cellular heart function by directly enhancing cardiac sarcoplasmic reticulum Ca2+ cycling. Circ Res 100:96–104; 2006.
- Bilchick K, Duncan JG, Ravi R, Takimoto E, Champion HC, Gao, WD, Stull LS, Kass DA, Murphy AM. Heart failure-associated alterations in troponin I phosphorylation impair left ventricular relaxation-afterload and force-frequency responses and systolic function. Am J Physiol Heart Circ Physiol 292:H318–25, 2007.
- Dai T, Tian Y, Tocchetti CG, Katori T, Murphy AM, Kass DA, Paolocci N, Gao WD. Nitroxyl anion (HNO/NO-) increases myofilament Ca2+ responsiveness in rat cardiac muscle. J Physiol 580(3): 951-960, 2007. (Editorial by RJ Solaro. Nitroxyl effects on myocardium provide new insights into the significance of altered myofilament response to calcium in the regulation of contractility. J Physiol 580(3):697, 2007)
- Gao WD, Muphy AM. Local control in thin filament activation of cardiac muscle. J Physiol 580(Pt. 2):358, 2007.
- Ramirez-Correa GA, Jin W, Wang Z, Zhong X, Gao WD, Dias WB, Vecoli C, Hart GW, Murphy AM. O-Linked GlcNAc modification of cardiac myofilament proteins: A novel regulator of myocardial contractile function. Circ Res 103:1354–8, 2008.
- 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.
- 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.
- 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.
- 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 14:1687–98, 2011.
- 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 339:825–31, 2011. (Highlighted paper)
- 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.
- 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. (Editorial by Y Ge and RL Moss. Nitroxyl, redox switches, cardiac myofilaments, and heart failure: a prequel to novel therapeutics? Circ Res 111(8):954-6, 2012).
- Shen X, Tan Z, Zhong X, Tian Y, Wang X, Yu B, Ramirez-Correa G, Murphy AM, Gabrielson KL, Paolocci N, Gao WD. Endocardial endothelium is a key determinant of force-frequency relationship in rat ventricular myocardium. J Appl Physiol in press, 2013. PMID: 23703113
Laboratory Members/Key Associates
Jonathan Kirk, PhD (Cardiology)
Xiaoxu Shen, MD, PhD
Yuejin Zhou, MD, PhD (Pediatrics)
Sonia Cortassa, PhD, Assistant Professor, Cardiology, JHU
David Kass, MD, Professor, Cardiolgy, JHU
Anne M. Murphy, MD, Professor, Pediatric Cardiology, JHU
Naz Paolocci, MD, PhD, Assistant Professor, Medicine/Cardiology, JHU
Genaro Ramirez-Correa, MD, PhD, Research Associate, Pediatric Cardiology, JHU
Jennifer van Eyk, PhD, Professor, Medicine/Cardiology/Biomedical Engineering/Biochemistry, JHU, and Director, NIH/NHLBI Proteomics Center at Hopkins
- William H. Davis Scholarship for Medical Research, Faculty of Graduate Studies, University of Calgary, Calgary, Canada (1989)
- International Research Fellowship, American Heart Association (1994)
- Clinician-Scientist Award, Johns Hopkins University School of Medicine (2002)