Emergency Medicine Research

Basic Science Research Program

Chief: Haichao Wang, PhD

Position:
Chief of Emergency Medicine Basic Science Program

Associate Investigator, The Feinstein Institute for Medical Research

Associate Professor, Emergency Medicine NYU School of Medicine

Vice Chairman, Institute Animal Care and Use Committee (IACUC) at the Feinstein Institute for Medical Research

Faculty, Graduate School of the Feinstein Institute for Medical Research

Member of Executive Editorial Board. International Journal of Clinical and Experimental Medicine, IJCEM

Member of Editorial Board, Shock.

Member of the Editorial Advisory Board, Inflammation & Allergy-Drug Targets / Mail Reviewer, NIH Special Emphasis Panel, Scientific Review Group 2009 / Member, NIH Study Section, RFA-OD-09-008 BRDG-SPAN and RFA-OD-09009 Catalyst ARRA Review Panel 14, 2010/01 Council ZRG1SBIB-D 53 R

Education:
MS: Zhejiang University, P.R. China
PhD: Louisiana State University, Baton Rouge, LA

The mission of the Departmental Basic Science Research Program is to discover the underlying causes of human diseases (such as sepsis and stroke), thereby bringing new knowledge into diagnostic and therapeutic solutions for Emergency Department patients. To that end, we ask clinically relevant questions and commit time and effort to develop research projects that will improve our understanding of the pathophysiology of human diseases, and that will help to identify novel therapeutic strategies. We are currently expanding our research program by obtaining additional federal funding and acquiring talented scientists to ensure continuous success. The continuous growth of our Basic Science Research Program is anticipated to yield sustained returns in the form of significant funding and prestige for the Department of Emergency Medicine, North Shore University Hospital, as well as the NSLIJ Health System.

Dr. Wang is a pioneer in cytokine research. He currently holds several patents for his research studying the effects of fetuin and other therapeutic agents on HMGB1 and other inflammatory cytokines. His groundbreaking studies on HMGB1 are acclaimed for advancing the academic knowledge surrounding immunology and inflammation management to alleviate disease propagation. Dr. Wang’s recent NIH R01 grant proposal, “Regulation of HMGB1 Release in Endotoxemia,” was recently funded by the Surgery, Anesthesiology and Trauma Study Section of the National Institute of Medical Sciences. Dr. Wang has also received R01 grant funding from the NIH for his proposal: “Neuroprotective role of fetuin in cerebral ischemia.” Dr. Wang recently submitted a R01 grant proposal to the NIH entitled, “Mechanisms of Novel Herbal Therapies for Sepsis.” He hopes to investigate the immunomodulatory mechanisms of common Chinese medicinal herbs to eventually develop alternative treatments for systemic inflammatory disease.

Haichao Wang, PhD presenting the abstract entitled “A Cardiovascular Chinese Herbal Medicine Rescues Mice from Lethal Sepsis by Selectively Attenuating a Late-Acting Proinflammatory mediator, HMGB1,” at the Society of Academic Emergency Medicine Annual Meeting held in Chicago, IL. in May 2007.

Sepsis is the leading cause of death among non-coronary ICU patients. Developing ways to therapeutically treat by slowing down and reversing the progression of sepsis remains to be a challenge for both physicians and researchers. Dr. Wang and his lab have continued to develop novel ways to treat sepsis at earlier stages of the disease with the hope of improving outcomes.

In addition to sepsis, Dr. Wang and his lab team have focused on the body’s inflammatory response to ischemic events with particular interest in cerebral ischemia and injury.

Dr. Wang’s Research Staff:

Wei Li, MD, PhD

Position – Research Scientist

Education:
M.D. – Henan Medical University, P.R. China

M.S. – Physiology, Henan Medical University, P.R. China

Ph.D. – Neuroscience, University of Manitoba, Canada

Shu Zhu, MD, PhD

Position – Research Scientist

Education:
M.D. – Changchun University of Chinese Medicine, P.R. China

M.S. – Internal Medicine, Changchun University of Chinese Medicine, P.R. China

Ph.D. – Internal Medicine, China Academy of Chinese Medical Science, P.R. China
Yan Huang

Yan Huang, MD, PhD

Position – Visiting Scholar from Xiangya Hospital, Central South University, China
Arvin Jundoria

Arvin Jundoria, BS:

Position – Research Assistant

Education:
B.S. - Stony Brook University

Dr. Wang and his students in the Laboratory of Emergency Medicine (summer 2008).
From left to right:
1) Haichao Wang, Ph.D.,
2) Rongrong Zhou, visiting Ph.D. graduate student from Xiangya Hospital, China;
3) Sudhat Ashok, summer internship student from Syosset, NY;
4) Sheena Tsai, summer Internship Student from Whitestone, NY.

Dr. Wang and his lab also support interns from local high schools as well as visiting graduate students from other nations. This past summer, Dr. Wang's lab grew to include two summer interns as well as a visiting postdoctoral student from China."

Patents held by Dr. Wang and his research staff:

  • Tracey KJ & Wang H. Usage of fetuin in prevention of pregnancy miscarriages. United States Patent No. 6011005 (Date of Patent: January 4, 2000).
  • Tracey KJ & Wang H. Usage of fetuin in inhibiting proinflammatory cytokine production. United States Patent No. 6117837 (Date of Patent: September 12, 2000).
  • Tracey KJ & Wang H. Complex and combinations of fetuin with therapeutic agents (CNI-1493). United States Patent No. 6319894 B1 (Date of Patent: November 20, 2001).
  • Tracey KJ & Wang H. Usage of fetuin in treatment of cerebral ischemic injury (stroke). United States Patent No.60/129,288 (Date of Patent: 2002).
  • Tracey KJ & Wang H. Antagonists of HMG-1 for treating inflammatory conditions. United States Patent No. 6468533 (Date of Patent: October 22, 2002).
  • Tracey KJ, Wang H, & Sama AE. Inhibition of HMGB1 release by fetuin (Filed on October 1, 2004).
  • Wang H, Sama AE, & Chen D. Inhibition of inflammatory cytokine production with tanshinones (Filed on January 12, 2007).

Dr. Wang and his research staff have recently published the following manuscripts:

  1. Botchkina GI, Zuniga ES, Das M, Wang Y, Wang H, Zhu S, Savitt AG, Rowehl RA, Leyfman Y, Ju J, Shroyer K and Ojima I (2010) New-generation taxoid SB-T-1214 inhibits stem cell-related gene expression in 3D cancer spheroids induced by purified colon tumor-initiating cells. Mol Cancer 9:192: 192.
  2. Kang R, Tang D, Yu Y, Wang Z, Hu T, Wang H and Cao L (2010) WAVE1 regulates Bcl-2 localization and phosphorylation in leukemia cells. Leukemia 24: 177-186.
  3. Wang H, Li W, Zhu S, Li J, D'Amore J, Ward MF, Yang H, Wu R, Jahnen-Dechent W, Tracey KJ, Wang P and Sama AE (2010) Peripheral administration of fetuin-A attenuates early cerebral ischemic injury in rats. J Cereb Blood Flow Metab 30: 493-504.
  4. Yang H, Hreggvidsdottir HS, Palmblad K, Wang H, Ochani M, Li J, Lu B, Chavan S, Rosas-Ballina M, Al Abed Y, Akira S, Bierhaus A, Erlandsson-Harris H, Andersson U and Tracey KJ (2010) A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release. Proc Natl Acad Sci USA 107: 11942-11947.
  5. Miksa M, Wu R, Dong W, Komura H, Amin D, Ji Y, Wang Z, Wang H, Ravikumar TS, Tracey KJ and Wang P (2009) Immature dendritic cell-derived exosomes rescue septic animals via milk fat globule epidermal growth factor-factor VIII. J Immunol 183: 5983-5990.
  6. Tang D, Kang R, Xiao W, Zhang H, Lotze MT, Wang H and Xiao X (2009) Quercetin prevents LPS-induced high-mobility group box 1 release and proinflammatory function. Am J Respir Cell Mol Biol 41: 651-660.
  7. Wu R, Dong W, Qiang X, Wang H, Blau SA, Ravikumar TS and Wang P (2009) Orexigenic hormone ghrelin ameliorates gut barrier dysfunction in sepsis in rats. Crit Care Med 37: 2421-2426.
  8. Zhu S, Ashok M, Li J, Li W, Yang H, Wang P, Tracey KJ, Sama AE and Wang H (2009) Spermine protects mice against lethal sepsis partly by attenuating surrogate inflammatory markers. Mol Med 15: 275-282.
  9. Huston JM, Wang H, Ochani M, Ochani K, Rosas-Ballina M, Gallowitsch-Puerta M, Ashok M, Yang L, Tracey KJ and Yang H (2008) Splenectomy protects against sepsis lethality and reduces serum HMGB1 levels. J Immunol 181: 3535-3539.
  10. Zhu, S., W. Li, J. Li, A.E. Sama, & H. Wang. (2008). Caging a beast in the inflammation arena: use of Chinese medicinal herbs to inhibit a late mediator of lethal sepsis, HMGB1. International Journal of Clinical and Experimental Medicine. 1: 64-79.
  11. Tang D, Kang R, Cao L, Zhang G, Yu Y, Xiao W, Wang H and Xiao X (2008) A pilot study to detect high mobility group box 1 and heat shock protein 72 in cerebrospinal fluid of pediatric patients with meningitis. Crit Care Med 36: 291-295.
  12. Ivanov S, Dragoi AM, Wang X, Dallacosta C, Louten J, Musco G, Sitia G, Yap GS, Wan Y, Biron CA, Bianchi ME, Wang H and Chu WM (2007) A novel role for HMGB1 in TLR9-mediated inflammatory responses to CpG-DNA. Blood 110: 1970-1981.
  13. Li W, Ashok M, Li J, Yang H, Sama AE and Wang H (2007) A Major Ingredient of Green Tea Rescues Mice from Lethal Sepsis Partly by Inhibiting HMGB1. PLoS ONE 2: e1153.
  14. Li W, Li J, Ashok M, Wu R, Chen D, Yang L, Yang H, Tracey KJ, Wang P, Sama AE and Wang H (2007) A cardiovascular drug rescues mice from lethal sepsis by selectively attenuating a late-acting proinflammatory mediator, high mobility group box 1. J Immunol 178: 3856-3864.
  15. Tang D, Kang R, Xiao W, Wang H, Calderwood SK and Xiao X (2007) The anti-inflammatory effects of heat shock protein 72 involve inhibition of high-mobility-group box 1 release and proinflammatory function in macrophages. J Immunol 179: 1236-1244.
  16. Tang D, Kang R, Xiao W, Jiang L, Liu M, Shi Y, Wang K, Wang H and Xiao X (2007) Nuclear heat shock protein 72 as a negative regulator of oxidative stress (hydrogen peroxide)-induced HMGB1 cytoplasmic translocation and release. J Immunol 178: 7376-7384.
  17. Qin S, Wang H, Yuan R, Li H, Ochani M, Ochani K, Rosas-Ballina M, Czura CJ, Huston JM, Miller E, Lin X, Sherry B, Kumar A, Larosa G, Newman W, Tracey KJ and Yang H (2006) Role of HMGB1 in apoptosis-mediated sepsis lethality. J Exp Med 203: 1637-1642.
  18. Wang H, Li W, Li J, Rendon-Mitchell B, Ochani M, Ashok M, Yang L, Yang H, Tracey KJ, Wang P and Sama AE (2006) The aqueous extract of a popular herbal nutrient supplement, Angelica sinensis, protects mice against lethal endotoxemia and sepsis. J Nutr 136: 360-365.
  19. Chen G, Li J, Qiang X, Czura CJ, Ochani M, Ochani K, Ulloa L, Yang H, Tracey KJ, Wang P, Sama AE and Wang H (2005) Suppression of HMGB1 release by stearoyl lysophosphatidylcholine:an additional mechanism for its therapeutic effects in experimental sepsis. J Lipid Res 46: 623-627.
  20. Cui X, Wu R, Zhou M, Dong W, Ulloa L, Yang H, Wang H, Tracey KJ, Simms HH and Wang P (2005) Adrenomedullin and its binding protein attenuate the proinflammatory response after hemorrhage. Crit Care Med 33: 391-398.
  21. Li, W., A.E. Sama, & H. Wang. (2006). Role of HMGB1 in cardiovascular disease. Current Opinion in Pharmacology 6(2): 130-135.
  22. Wang, H., M.F. Ward, X.G. Fan, A.E. Sama, & W. Li. (2006). Potential role of HMGB1 in virnfectious diseases. Viral Immunology 19(1): 3-9.
  23. Yang, H., H. Wang, C. Czura, & K.J. Tracey. (2005). The cytokine activities of HMGB1. Journal of Leukocyte Biology 76(7): 1-8.
  24. Chen G, Li J, Ochani M, Rendon-Mitchell B, Qiang X, Susarla S, Ulloa L, Yang H, Fan S, Goyert SM, Wang P, Tracey KJ, Sama AE and Wang H (2004) Bacterial endotoxin stimulates macrophages to release HMGB1 partly through CD14- and TNF-dependent mechanisms. J Leukoc Biol 76: 994-1001.
  25. Sama, A.E., M. Ward, J. D'Amore, G. Chen, and H. Wang. (2004).HMGB1: a novel proinflammatory cytokine and therapeutic target for septic patients in the Emergency Medicine. Academic Emergency Medicine 11: 867-873.
  26. Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L, Al Abed Y, Wang H, Metz C, Miller EJ, Tracey KJ and Ulloa L (2004) Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med 10: 1216-1221.
  27. Yang H, Ochani M, Li J, Qiang X, Tanovic M, Harris HE, Susarla SM, Ulloa L, Wang H, DiRaimo R, Czura CJ, Wang H, Roth J, Warren HS, Fink MP, Fenton MJ, Andersson U and Tracey KJ (2004) Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci U S A 101: 296-301.
  28. Rendon-Mitchell B, Ochani M, Li J, Han J, Wang H, Yang H, Susarla S, Czura C, Mitchell RA, Chen G, Sama AE, Tracey KJ and Wang H (2003) IFN-gamma induces high mobility group box 1 protein release partly through a TNF-dependent mechanism. J Immunol 170: 3890-3897.
  29. Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Wang H, Yang H, Ulloa L, Al Abed Y, Czura CJ and Tracey KJ (2003) Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421: 384-388.
  30. Ombrellino M, Wang H, Ajemian MS, Talhouk A, Scher LA, Friedman SG and Tracey KJ (1999) Increased serum concentrations of high-mobility-group protein 1 in haemorrhagic shock [letter]. Lancet 354: 1446-1447.
  31. Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, Frazier A, Yang H, Ivanova S, Borovikova L, Manogue KR, Faist E, Abraham E, Andersson J, Andersson U, Molina PE, Abumrad NN, Sama A and Tracey KJ (1999) HMG-1 as a late mediator of endotoxin lethality in mice. Science 285: 248-251.
  32. Ivanova S, Botchkina GI, Al-Abed Y, Meistrell M, Batliwalla F, Dubinsky JM, Iadecola C, Wang H, Gregersen PK, Eaton JW and Tracey KJ (1998) Cerebral ischemia enhances polyamine oxidation: identification of enzymatically formed 3-aminopropanal as an endogenous mediator of neuronal and glial cell death. J Exp Med 188: 327-340.
  33. Wang H, Zhang M, Bianchi M, Sherry B, Sama A and Tracey KJ (1998) Fetuin (alpha2-HS-glycoprotein) opsonizes cationic macrophagedeactivating molecules. Proc Natl Acad Sci U S A 95: 14429-14434.
  34. Wang H, Zhang M, Soda K, Sama A and Tracey KJ (1997) Fetuin protects the fetus from TNF [letter]. Lancet 350: 861-862.
  35. Zhang M, Caragine T, Wang H, Cohen PS, Botchkina G, Soda K, Bianchi M, Ulrich P, Cerami A, Sherry B and Tracey KJ (1997) Spermine inhibits proinflammatory cytokine synthesis in human mononuclear cells: a counterregulatory mechanism that restrains the immune response. J Exp Med 185: 1759-1768.

Dr. Wang and his research staff have recently published the following review articles:

  1. Zhu, S., W. Li, M.F. Ward, A.E. Sama, and H. Wang. (2010). HMGB1 as a potential drug target for infection- and injury-elicited inflammatory responess. Inflammation and Allergy - Drug Targets. 9(1): 60-72 (journal featured article).
  2. Wang, H., M. Ward, & A.E. Sama (2009). Novel HMGB1-inhibiting therapeutic agents for experimental sepsis. Shock. 32(4): 348-357.
  3. Wang H, Zhu S, Zhou R, Li W and Sama AE (2008) Therapeutic potential of HMGB1-targeting agents in sepsis. Expert Rev Mol Med 10:e32.: e32.
  4. Zhu, S., W. Li, J. Li, A.E. Sama, & H. Wang. (2008). Caging a beast in the inflammation arena: use of Chinese medicinal herbs to inhibit a late mediator of lethal sepsis, HMGB1. International Journal of Clinical and Experimental Medicine 1: 64-79
  5. Wang H, Zhu S, Ward MF, Gong J and Sama AE (2008) Hyperglycemia aggravates endotoxin-induced high mobility group box 1 protein release: yet another reason not to be too sweet. Crit Care Med 36: 2475-2476.
  6. Wang, H., M.F. Ward, X.G. Fan, A.E. Sama, & W. Li. (2006). Potential role of HMGB1 in viral infectious diseases. Viral Immunology 19(1): 3-9 .
  7. Li W, Sama AE and Wang H (2006) Role of HMGB1 in cardiovascular diseases. Curr Opin Pharmacol 6: 130-135.
  8. Yang, H., H. Wang, C. Czura, & K.J. Tracey. (2005). The cytokine activities of HMGB1. Journal of Leukocyte Biology 76(7): 1-8.
  9. Sama, A.E., M. Ward, J. D'Amore, G. Chen, and H. Wang. (2004). HMGB1: a novel proinflammatory cytokine and therapeutic target for septic patients in the Emergency Medicine. Academic Emergency Medicine 11: 867-873.
  10. Wang H, Yang H and Tracey KJ (2004) Extracellular role of HMGB1 in inflammation and sepsis. J Intern Med 255: 320-331.
  11. Wang H, Czura CJ and Tracey KJ (2004) Lipid unites disparate syndromes of sepsis. Nat Med 10: 124-125.
  12. Wang H, Yang H, Czura CJ, Sama AE and Tracey KJ. (2001). HMGB1 as a Late Mediator of Lethal Systemic Inflammation. Am J Respiratory and Crit Care Med 164: 1768-1773.
  13. Zhang M, Wang H and Tracey KJ (2000) Regulation of macrophage activation and inflammation by spermine: a new chapter in an old story. Crit Care Med 28: N60-N66.

Dr. Wang and his research staff have recently published the following book chapters:

  1. Wang, H, W. Li, R. Goldstein, K.J. Tracey, & A.E. Sama. (2007). HMGB1 as a potential therapeutic target. In: Novartis Foundation Symposium 280: Sepsis – New Insights, New Therapies. pp73-91, New York: John Wiley & Sons.
  2. Li, W., J. Li., M.F. Ward, A.E. Sama, and H. Wang. (2006). Discovery of HMGB1 as a self-destructive nuclear weapon in lethal sepsis. In: Recent Research Development in Experimental Medicine, 2nd Issue. Transworld Research Network, Kerala, India.
  3. Wang H, Czura C.J. and Tracey K.J. (2003) HMGB1. In: Thomson A and Lotze MT (eds) The Cytokine Handbook, pp 913-923. Academic Press, Oxford.
  4. Wang H, Czura C.J. and Tracey K.J. (2003) TNF. In: Thomson A and Lotze MT (eds) The Cytokine Handbook, pp 837-860. Academic Press, Oxford.
  5. Wang H and Tracey KJ (1999) TNF, IL-6, MIF and MIP-1 in inflammation. In: Gallin JI and Snyderman R (eds) Inflammation: Basic Principles and Clinical Correlates, pp 471-486. Lippincott-Racen Press, Philadelphia.

Dr. Wang was invited to the following lectures:

  1. "Fetuin-A protects mice against lethal sepsis by modulating endotoxin-induced HMGB1 release and autophagy." Symposium: Immunomodulatory therapy of sepsis - The next great advance? The 8th World Congress on Trauma, Shock, Inflammation and Sepsis - Interdisciplinary Summit on Inflammation. March 9-13, 2010, Munich, Germany.
  2. "HMGB1." Symposium: Monitoring the immunoinflammatory response in critical illness: My favorite biomarker(s)/analytical advices for clinical use - Part B. The 8th World Congress on Trauma, Shock, Inflammation and Sepsis - Interdisciplinary Summit on Inflammation. March 9-13, 2010, Munich, Germany.
  3. "Inhibiting A Late Mediator of Lethal Sepsis, HMGB1, with Anti-cancer Chinese Medicinal Herbs." Department of Emergency Medicine, Xijing Hospital, The 4th Medical University, Xi'an, Shaanxi, P. R. China (August 26, 2010, Invited by Dr. Wen Yi).
  4. "Challenge for Experimental Validation of Traditional Chinese Medicine in the Western World: Exploration of Chinese Medicinal Herbs as Potential HMGB1-targeting Therapies for Sepsis." School of Radiation Medicine and Public Health, Soochow University, Jiangsu, P. R. China (November 11, 2010, Invited by Dr. Saijun Fan).
  5. "A decade of search for potential therapeutic target and agents for experimental sepsis.” Department of Pulmonary and Critical Medicine, Louisiana State University Health Science Center, New Orleans, LA, October 21, 2009.
  6. “Caging the beast (HMGB1) in the inflammation arena” Department of Cell Biology, University of Alabama, Birmingham, AL, April 22-24, 2008.

Dr. Wang's team has recently presented the following abstracts:

  1. W. Li, J. Li, M. Ashok, S. Zhu, A.E. Sama, & H. Wang. (2010). Carbenoxolone Rescues Mice from Lethal Sepsis by Inhibiting HMGB1 Release. Academic Emergency Medicine.
  2. H. Wang, W. Li, S. Zhu, J. Li, M.F. Ward, Y. Huang, H. Yang, K.J. Tracey, P. Wang, and A.E. Sama. (2010). Fetuin Protects Mice Against Lethal Sepsis by Modulating Bacterial Endotoxin-Induced HMGB1 Release and Autophagy. Shock Vol. 33 (Suppl 1): 6.
  3. S. Zhu, J. Li, W. Li, M. Ashok, A.E. Sama, & H. Wang. (2010). The aqueous extract of Mung bean SKIN (Vigna radiata) protects mice against lethal sepsis.  Shock Vol. 33 (Suppl 1): 69.
  4. W. Li, J. Li, M. Ashok, S. Zhu, A.E. Sama, & H. Wang. (2010). Carbenoxolone Rescues Mice from Lethal Sepsis by Inhibiting HMGB1 Release. Shock Vol. 33 (Suppl 1): 69
Abstracts Presented

Dr. Wang receives an Honorary Professorship at Xiangya Hospital, China.

Dr. Wang receives an Honorary Professorship at Xiangya Hospital, China.
In 2006, Dr. Wang was awarded an Honorary Professorship at the Xiangya Hospital, China. Xiangya Hospital is the Yale-in-China clinic established by Yale University’s Dr. Edward Hume in 1906. It is one of the largest teaching hospitals in Asia, and is an academic campus for the Central South University School of Basic Medicine.

Dr. Wang will be participating in the following International Conferences:

  • Faculty member of the scientific program committee, the 8th World Congress on Trauma, Shock, Inflammation and Sepsis – Interdisciplinary Summit on Inflammation, March 13-17, 2010, Munich, Germany.

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