Gong Zhao
*** ****** ***** **., *******, CA *****
Phone: 650-***-**** (O), 510-***-**** (H)
Fax: 650-***-**** (O), 510-***-**** (H), E-mail: ************@*******.***
PROFESSIONAL HISTORY:
4/2009 present: Gilead Sciences Palo Alto, 1651 Page Mill Road, Palo Alto, CA 94304
4/2009-present: Senior Research Scientist
1/2001 4/2009 Pharmacological Sciences, CV Therapeutics, Inc., 3172 Porter Drive, Palo Alto, CA 94304 (Acquired by Gilead Sciences in April, 2009)
7/2008 4/2009 Senior Scientist
7/2005 6/2008 Scientist III
1/2003 6/2005 Scientist II
1/2001 12/2002 Scientist I
8/1992 12/2000: Department of Physiology, New York Medical College, Valhalla, NY 10595
10/1999 12/2000 Research Assistant Professor,
12/1994 10/1999 Instructor
8/1992 11/1994 Postdoctoral Fellow
EDUCATION:
M.D. 1983, Department of Medicine, Hebei Medical College, China
Ph.D 1990, Department of Physiology, Hebei Medical College, China (Cardiovascular Physiology)
I am involved in research activities of preclinical pharmacology (in vivo and in vitro) to support filings to the US FDA and European Authority Agencies. In vivo studies are performed in conscious dogs, conscious rabbits, awake and anesthetized rats to determine cardiovascular safety and efficacy for a number of products. In addition, pharmacokinetic studies are performed in conscious dogs and rats.
During my work at CV Therapeutics and Gilead for more than 10 years, a number of papers have been published in peer-reviewed journals and some have been submitted for consideration for publication. A number of abstracts have been presented by oral or poster in national and international meetings including ACC, WCC and FASEB (Experimental Biology) meetings. A number of technical reports have been finished and most of them have been submitted to the US FDA and European Medicines Agencies as supports of NDA (New Drug Application) or MAA (Marketing Authorization Application). These technical reports provided strong and solid preclinical pharmacology and cardiovascular safety data to support the two drugs’ (ranolazine and regadenoson) approval by the USA FDA and MAA, respectively.
Project management experience: Managing/managed three contract projects (two in New York Medical College and one in University Nebraska Medical Center at Omaha) including making budget plans and research plans, designing studies, writing research protocols, data analysis and so on.
Supervisory experience: I have one direct report (an Associate Scientist) in house (Gilead).
Supervising two technicians and one postdoctoral fellow doing projects in conscious dogs for the company in Dr. Thomas Hintze's lab at New York Medical College (from 2003 to present).
Trained 6 people in cardiovascular physiology/pharmacology research since 2001
2001: Axel Linke, PhD
2003 2004: Erin Walsh, MS
2004 2006: Eric Messina, (MS student)
2006 2007: Sabrina Serpillon, PhD
2007 2008: Suhua Zhang, MD
2009 2011: Shu Song, PhD student
Projects completed:
A. In mice:
1. Effects of Gilead-compound on glucose concentrations in blood in normal and diabetic mice
B. In rats:
1. Effects of Gilead-compound on glucose concentrations in blood in normal and Streptozotocin-induced diabetes in awake rats
2. Effects of free fatty acid on blood pressure and heart rate in awake and anesthetized rats
3. Effects of Gilead-compounds on blood pressure and heart rate in awake and anesthetized rats
4. Mechanism of Chloro-IB-MECA-induced histamine release and subsequent cardiovascular effects in awake rats
5. Impairment of nitric oxide-dependent vasodilation in the femoral artery in Zucker diabetic rats and restoration by Gilead-compounds
6. Inhibition of the adenosine-induced vasorelaxation by Gilead-compounds in the aortic rings from the rat
C. In conscious dogs:
1. Effects of ranolazine on systemic hemodynamics and coronary circulation in conscious dogs
2. Effects of ranolazine on isosorbide dinitrate- or sildenafil-induced changes in blood pressure and heart rate in conscious dogs
3. Effects of regadenoson on cardiac output and regional blood flow in conscious dogs.
4. Effects of caffeine on regadenoson-induced coronary vasodilation and changes in hemodynamics in conscious dogs
5. Effects of regadenoson on Q-T interval and its mechanism in conscious dogs
6. Anti-adrenergic effects of ranolazine in conscious dogs
7. Effects of Dipyridamole on hemodynamics, coronary blood flow and cytokines in conscious dogs
8. Comparison of regadenoson in two vehicles: Effects on hemodynamics and coronary circulation in conscious dogs
9. Comparison of ranolazine with its two enantiomers in conscious dogs: Effects on hemodynamics, coronary blood flow, and the antagonism of α- and β-adrenergic receptor-mediated responses
10. Effects of metoprolol on the regadenoson-induced changes in hemodynamics and coronary circulation in conscious dogs
11. Effects of aminophylline on the regadenoson-induced changes in hemodynamics and coronary circulation in conscious dogs
12. Effects of the duration of iv injection on the regadenoson-induced changes in hemodynamics and coronary circulation in conscious dogs
13. Effects Gilead-compound on systemic and coronary circulation in conscious dogs
14. Anti-adrenergic effects of combination of ranolazine and dronedarone in conscious dogs
15. Mechanism(s) of ranolazine-induced transient hemodynamic changes in conscious dogs
Disease Models
1. Alloxan-induced diabetes in conscious dogs
2. Pacing-induced heart failure in conscious dogs
3. Streptozotocin-induced diabetes in conscious rats
Technical Skills
1. In dogs: Surgical skills to implant different instruments in dogs for measurements of hemodynamic parameters, cardiac functions, coronary and peripheral artery flow. Perform various experiments in conscious dogs for cardiovascular safety and efficacy.
2. In rabbits and rats: Surgical skills to implant different instruments in rats for measurements of hemodynamic parameters, cardiac functions and regional arterial blood flow in anesthetized and conscious rabbits and rats, as appropriate.
3. In vitro: Measurement of tension of vessels ring from rats; Measurement of O2 consumption of muscle slices; Measurements of free fatty acid, glucose and lactate using commercial kits.
More than 8 years, experience focused on the role of nitric oxide (NO) in reflex regulation of coronary circulation in different physiologic and pathophysiologic conditions such as exercise training, heart failure and diabetes. Animal models used in Dr. Thomas Hintze’s lab were pacing-induced heart failure and alloxan-induced diabetes in conscious dogs. Most importantly, I developed alloxan-induced diabetes model in the lab and the preliminary data obtained using the diabetic model in conscious dogs led to a NIH grant finding for Dr. Hintze (myself was the co-invastigator).
HONORS AND AWARDS:
1. Grant-in-Aid, American Heart Association, New York Affiliate, 1996-1998. P.I.
Effects of exercise training on vagally mediated, NO-dependent coronary vasodilation in conscious dogs.
2. Intramural grant of New York Medical College, 1996-1997. P.I.
Reflex NO-dependent coronary vasodilation in diabetes.
REVIEWERS
Grader for 69th, 72nd, 73rd and 74th Scientific Meeting Abstract, American Heart Association.
Reviewer for
Prostaglandins
American Journal of Physiology (Heart)
Life Science
Diabetes
European Journal of Pharmacology
Biochemical Pharmacology
Reports in Medical Imaging
Therapeutics and Clinical Risk Management
Vascular Health and Risk Management
PUBLICATIONS:
Research Papers
1. Jie Wang, Gong Zhao, Weiqun Shen, Manuel Ochoa, Dennis Moore and Thomas H. Hintze. Effects of an orally active NO-releasing agent, CAS 936, and its active metabolite, 3754, on cardiac and coronary dynamics in normal conscious dogs and after pacing-induced heart failure. J. Cardiovasc. Pharmacol. 1993;22(Suppl. 7):S51-S58
2. Weiqun Shen, Xiaobin Xu, Manuel Ochoa, Gong Zhao, Michael S. Wolin and Thomas H. Hintze. Role of nitric oxide in the regulation of oxygen consumption in conscious dogs. Circ. Res. 1994;75:1086-1095
3. Gong Zhao, Weiqun Shen, Xiaobin Xu, Manuel Ochoa, Robert Bernstein and Thomas H. Hintze. Selective impairment of vagally mediated, nitric oxide-dependent coronary vasodilation in conscious dogs after pacing-induced heart failure. Circulation 1995;91:2655-2663
4. Weiqun Shen, Xiaoping Zhang, Gong Zhao, Michael S. Wolin, William Sessa and Thomas H. Hintze. Nitric oxide production and upregulation of NO synthase gene expression contribute to vascular regulation during exercise and may be responsible for the beneficial vascular effects of aerobic exercise training. Med. Sci. Sport Exer. 1995;27:1125-1134.
5. Smith CJ, Sun D, Hoegler C, Roth BS, Zhang XP, Zhao G, Xu XB, Kobari Y, Pritchard K, Sessa WC and Hintze TH. Reduced gene expression of vascular endothelial nitric oxide synthase and cyclo-oxgenase-1 in heart failure. Circ. Res. 1996;78:58-64.
6. Yiwu Xie, Weiqun Shen, Gong Zhao, Xiaobin Xu, Michael S. Wolin and Thomas H. Hintze. Role of endothelium derived nitric oxide in the modulation of canine myocardial mitochondrial respiration in vitro: implication for the development of heart failure. Circ. Res. 1996;79:381-387.
7. Gong Zhao, Weiqun Shen, Xiaoping Zhang, Carolyn J Smith and Thomas H Hintze. Loss of nitric oxide production in the coronary circulation after the development of dilated cardiomyopathy: A specific defect in the neural regulation of coronary blood flow. Clin. Exp. Pharmacol. Physiol. 1996;23:715-721.
8. Gong Zhao, Xiaobin Xu, Manuel Ochoa, Weiqun Shen and Thomas H. Hintze. Interaction between prostacyclin and nitric oxide in the reflex control of the coronary circulation in conscious dogs. Cardiovasc. Res. 1996;32(5):940-948.
9. Gong Zhao, Xiaoping Zhang, Xiaobin Xu, Manuel Ochoa, Thomas H Hintze. Short-term exercise training enhances reflex cholinergic, NO-dependent coronary vasodilation in conscious dogs. Circ. Res. 1997;80:868-876.
10. Robert D. Bernstein, Xiaoping Zhang, Gong Zhao, Paul Forfia, Joshua Tuzman, Francica Ochoa, Manuel Ochaoa, Traci Vogel and Thomas H. Hintze. Mechanisms of nitrate accumulation in plasma during pacing-induced heart failure in conscious dogs. Nitric Oxide: Biol. and Chem. 1997;1:386-396.
11. Gong Zhao, Xiaoping Zhang, Carolyn J, Smith, Xiaobin Xu, Manuel Ochoa, David Greenhouse, Traci Vogel, Christine Curran and Thomas H. Hintze. Reduced coronary NO production in conscious dogs after the development of alloxan-induced diabetes. Am. J. Physiol. 1999;277:H268-H278.
12. Dong Sun, An Huang, Gong Zhao, Robert Bernstein, Paul Forfia, Xiaobin Xu, Akos Koller, Gabor Kaley and Thomas Hintze. Reduced NO-dependent arteriolar dilation during the development of cardiomyopathy. Am. J. Physiol. 2000;278:H461-H468.
13. W. Shen, X. Xu, M. Ochoa, G. Zhao, R. D. Bernstein, P. Forfia and T. H. Hintze. Endogenous nitric oxide in the control of skeletal muscle oxygen extraction during exercise. Acta Physiol. Scand. 2000;168:675-686.
14. Gong Zhao, Xiaoping Zhang, Xiaobin Xu, Michael S. Wolin and Thomas H. Hintze. Depreesed modulation of O2 consumption by endogenous nitric oxide in cardiac muscle from diabetic dogs. Am. J. Physiol. 2000;279:H520-H527.
15. Seema Mital, Xiaoping Zhang, Gong Zhao, Robert D. Bernstein, Carolyn J, Smith, David Fulton, William C. Sessa, James Liao and Thomas H. Hintze. Simvastatin upregulates coronary vascular endothelial nitric oxide production in conscious dogs. Am. J. Physiol. 2000;279:H2649-H2657.
16. Jean-Noel Trochu, Gong Zhao, Heiner Post, Xiaobin Xu, Luiz Belardinelli Francis Belloni and Thomas Hintze. Selective A2A adenosine receptor agonist as a coronary vasodilator in conscious dogs: Potential for use in myocardial perfusion imaging. J Cardiovasc. Pharmacol. 2003;41:132-139.
17. Axel Linke, Gong Zhao, Fabio A. Recchia, Jeffrey Williams, Xiaobin Xu, and Thomas H. Hintze. Shift in metabolic substrate uptake by the heart during development of alloxan-induced diabetes. Am J Physiol Heart Circ Physiol, 2003;285:H1007-1014.
18. Gong Zhao, Axel Linke, Xiaobin Xu, Manuel Ochoa, Francis Belloni, Luiz Belardinelli and Thomas Hintze. Comparative profile of vasodilation by CVT-3146, a novel A2a receptor agonist, and adenosine in conscious dogs. J Pharmacol Exp Ther 2003;307:182-189.
19. Gong Zhao, Eric Messina, Xiaobin Xu, Manuel Ochoa, Sobrina Serpillon, John Shryock, Luiz Belardinelli and Thomas Hintze. Ranolazine, a novel anti-anginal agent, does not alter isosorbide dinitrate- or sildenafil-induced changes in blood pressure in conscious dogs. J Eur Pharmacol 2006;541:171-176.
20. Gong Zhao, Eric Messina, Xiaobin Xu, Manuel Ochoa, Hai-ling Sun, Kwan Leung, John Shryock, Luiz Belardinelli and Thomas Hintze. Caffeine attenuates the duration of coronary vasodilation and changes in hemodynamics induced by regadenosine (CVT-3146), a novel adenosine A2a agonist. J Cardiovasc Pharmacol 2007;49:369-375.
21. Gong Zhao, Sabrina Serpillon, John Shryock, Eric Messina, Xiaobin Xu, Manuel Ochoa, Luiz Belardinelli and Thomas Hintze. Regadenoson, a novel A2a adenosine receptor agonist, has no direct effect on the QT interval and heart rate in conscious dogs. J Cardiovasc Pharmacol 2008;52:467-473.
22. Gong Zhao, Erin Walsh, John C Shryock, Eric Messina, Yuzhi Wu, Dewan Zeng, Xiaobin Xu, Manuel Ochoa, Stephen Baker, Thomas H. Hintze, and Luiz Belardinelli, Antiadrenergic and hemodynamic effects of ranolazine in conscious dogs. J Cardiovasc Pharmacol. 2011;57:639-647.
23. Gong Zhao, Suhua Zhang, John C. Shryock, Xiaobin Xu, Manuel Ochoa, Thomas H. Hintze, and Luiz Belardinelli. Selective action of metoprolol to attenuate regadenoson-induced tachycardia in conscious dogs. J Nucl Cardiol. 2011 (in revision).
24. Gong Zhao, Dewan Zeng, Hongyan Zhong, Tenning Maa, John Shryock and Luiz Belardinelli. Activation of A3 adenosine receptor and sequential hemodynamic effects in awake rats. (In preparation).
Review Articles and Book Chapters
1. Thomas H. Hintze, Weiqun Shen, Nahid Seyedi and Gong Zhao. Potential roles for changes in coronary and myocyte nitric oxide production in the development of heart failure. Heart Failure 1994;10:116-125.
2. Gong Zhao, Thomas H. Hintze and Gabor Kaley. Neural regulation of coronary vascular resistance: Role of nitric oxide in reflex cholinergic coronary vasodilation in normal and pathophysiologic states. In: M. Karmazyn ed. Myocardial ischemia: Mechanisms, reperfusion, protection. Birkhauser Verlag, Switzerland. 1996:1-19.
3. Sarra K. Lacock, Xiaoping Zhang, Nahid Seyedi, Gong Zhao, Robert D. Bernstein, Thomas H. Hintze. Altered oxygen availability and the role of nitric oxide in the development of heart failure. In Bittar EE ed. Advances in organ biology. 1998;4A:172-192.
4. Gong Zhao, Robert D. Bernstein and Thomas H. Hintze. Nitric oxide and oxygen utilization: exercise, heart failure and diabetes. Coronary Artery Dis. 1999;10:315-320.
Technical Reports:
1. Gong Zhao and Luiz Belardinelli. Effects of ranolazine on systemic hemodynamics and coronary circulation in conscious dogs. Technical Report, CVT303.067-P (2003).
2. Gong Zhao. Effects of ranolazine on isosorbide dinitrate- or sildenafil-induced changes in blood pressure and heart rate in unanesthetized dogs. Technical Report, CVT303.105-P (2004).
3. Gong Zhao. Effects of Adenosine A2B Receptor Antagonists on Blood Pressure and Heart Rate in Awake Rats. Technical Report (2004)
4. Gong Zhao. Effects of caffeine on regadenoson-induced coronary vasodilation and changes in hemodynamics in conscious dogs. Technical Report, CVT3146.130-P (2006)
5. Gong Zhao. Effects of regadenoson (CVT-3146), a novel A2a adenosine receptor agonist, on Q-T interval. Technical Report, CVT3146.134-P (2007)
6. Gong Zhao. Anti-adrenergic effects of ranolazine in conscious dogs. Technical Report, CVT303.148-P (2007).
7. Gong Zhao and Hongyan Zhong. Effects of Dipyridamole on Hemodynamics, Coronary Blood Flow and Cytokines in Conscious Dogs. Technical Report (2007)
8. Gong Zhao. Comparison of regadenoson (CVT-3146) in two vehicles: Effects on hemodynamics and coronary circulation in conscious dogs. Technical Report, CVT3146.155-P (2008)
9. Gong Zhao Comparison of ranolazine with its two enantiomers in conscious dogs: Effects on hemodynamics, coronary blood flow, and the antagonism of α- and β-adrenergic receptor-mediated responses. Technical Report, CVT303.166-P-RTv1 (2008)
10. Gong Zhao Effects of metoprolol on the regadenoson-induced changes in hemodynamics and coronary circulation in conscious dogs. Technical Report, PC-260-2001 (2010)
11. Gong Zhao. Effects of aminophylline on the regadenoson-induced changes in hemodynamics and coronary circulation in conscious dogs. Technical Report, PC-260-2002 (2010)
12. Gong Zhao. Effects of the duration of iv injection on the regadenoson-induced changes in hemodynamics and coronary circulation in conscious dogs. Technical Report, PC-260-2003 (2010)