Haichao Wang, PhD

Investigator, The Feinstein Institute for Medical Research

Director, Laboratory of Emergency Medicine, The Feinstein Institute for Medical Research

Professor of Emergency Medicine, Hofstra Northwell School of Medicine

Phone: (516) 562-2823
Email: hwang@northwell.edu

About the Investigator

Dr. Wang is currently the chief of the Basic Science Research Program in the Department of Emergency Medicine at North Shore University Hospital. He also serves as a professor of molecular medicine at the Elmezzi Graduate School, and the director of the Laboratory of Emergency Medicine at the Feinstein Institute for Medical Research.

He earned a BS degree in biology from Hebei University in 1984, and then completed an MS degree in microbiology at Zhejiang University in 1987. In 1992, Dr. Wang received his PhD in microbiology from Louisiana State University, and subsequently finished a three-year postdoctoral fellowship in cell biology at the University of North Carolina-Chapel Hill. In 1995, Dr. Wang joined the Department of Emergency Medicine at North Shore University Hospital as the chief of the Basic Science Research Program.

Since 2002, Dr. Wang has obtained several R01 grants from the National Institute of General Medical Science (R01GM063075 and R01GM070817) and the National Center of Complementary and Alternative Medicine (R01AT005076). He has procured several patents regarding the use of acute phase proteins (e.g., fetuin and serum amyloid A) and herbal components (such as tanshinone IIA) as a potential therapeutic targets and agents. Since 1997, Dr. Wang has published 130 peer-reviewed research and review articles, which have been cited more than 15,900 times, according to the Web of Science (with an h-index = 51).

Dr. Wang currently serves as a referee for 40 journals, and editorial board member for five scientific journals (including Shock, Inflammation & Allergy – Drug target, SOJ Immunology, and Military Medical Research). Since 2009, he serves as a Reviewer / Member of multiple NIH Special Emphasis Panels. Dr. Wang also plays an active role in international conferences by serving as a co-moderator and invited speaker at several international shock and sepsis conferences.

He has not focused all of his energies solely on research, but has made significant contributions to academia and the advancement of knowledge to the future of biomedical research. Dr. Wang is currently mentoring postdoctoral fellows and high school students who have been named semifinalists in several international science competitions.

Research Focus

Dr. Wang’s research is intended to uncover the intricate mechanisms underlying the pathogenesis of human inflammatory diseases including cerebral ischemic injury and sepsis, two hot topics of the emergency medicine research. To that end, he is interested in identifying novel therapeutic targets and/or agents to fight against severe injury- and infection-elicited dysregulated inflammation. One outgrowth of this effort was the seminal discovery of a ubiquitous nucleosomal protein, HMGB1, as a critical late mediator of lethal inflammatory diseases (Science 1999, 285: 248-251). Currently, he is investigating the molecular mechanisms of HMGB1 release by identifying its negative (inhibiting) and positive (stimulating) regulators. This line of investigation led to the discovery of innate immune cell-derived pro-inflammatory cytokines (e.g., IFN-gamma) and liver-derived acute phase proteins (such as fetuin-A and serum amyloid A) as important regulators of HMGB1 release. He is also interested in investigating the biological roles of various acute phase proteins in animal models of inflammatory diseases (such as endotoxemia, sepsis, and rheumatoid arthritis).

Another outgrowth of the project was the discovery of major components of several Chinese herbs including Danggui (Angelica sinensis), Danshen (Salvia miltiorrhiza), Green tea (Camellia sinensis), and Gancao (Radix glycyrrhizae), that effectively attenuate HMGB1 release and confer protection against lethal endotoxemia and sepsis. He is interested in uncovering the novel pharmacological mechanisms by which these herbal ingredients block HMGB1 release at molecular and cellular.

His laboratory has been closely collaborating with the North Shore University Hospital Emergency Medicine Department for more than 17 years. This joint venture encourages his team to ask clinically relevant scientific questions, enabling us to uncover the intricate mechanisms of innate immune regulation, and to develop potential therapeutics for human inflammatory diseases.

Severe sepsis is an overwhelming systemic inflammatory response to infection, claiming approximately 225,000 victims annually in the U.S. alone. Its high mortality is in part mediated by dysregulated inflammatory responses manifested by the excessive accumulation of various pro-inflammatory cytokines. To uncover the mechanisms underlying the pathogenesis of sepsis, he has been attempting to identify novel therapeutic targets and/or agents for this disease since 1996. One outgrowth of this effort was the seminal discovery of a ubiquitous nucleosomal protein, HMGB1, as a critical late mediator of lethal endotoxemia (Science 1999, 285: 248-251). This groundbreaking finding laid down a foundation for further uncovering the intricate mechanisms of innate immune regulation, and stimulated an interest in developing novel therapeutic strategies for sepsis and other inflammatory diseases.

Project 1: Regulation of HMGB1 release in Endotoxemia.

Dr. Wang is investigating the molecular mechanisms of HMGB1 release by identifying potential endogenous negative (inhibiting) and positive (stimulating) regulators. This line of investigation led to the discovery of several innate immune cell-derived pro-inflammatory cytokines (e.g., IFN-gamma) and liver-derived acute phase proteins (such as fetuin-A and serum amyloid A) as important HMGB1 regulators. Moving forward, he is investigating the intricate mechanisms by which these cytokines and acute phase proteins regulate HMGB1 release, and influence the pathological outcomes in animal models of endotoxemia and sepsis.

Project 2: Mechanisms of Novel Herbal Therapies for Sepsis.

Many Chinese herbs belong to the realm of complementary and alternative medicine, and have been traditionally used for treating various inflammatory diseases. To further elucidate mechanisms underlying the pathogenesis of sepsis, we have screened >50 commonly used medicinal herbs for potential HMGB1-inhibiting properties. Among them, the major components of several Chinese herbs including Danggui (Angelica sinensis), Danshen (Salvia miltiorrhiza), Green tea (Camellia sinensis) and Gancao (Radix glycyrrhizae) effectively attenuate HMGB1 release, and confer protection against lethal endotoxemia and sepsis. He is now uncovering the novel and distinct mechanisms by which various herbal ingredients block HMGB1 release at molecular and cellular levels. Moreover, He will also explore their therapeutic potential using various animal models of inflammatory diseases, with particular attempt to advance the efficacy from employing nanotechnology and other chemical strategies.

In summary, the investigation of novel inflammatory mediators and their inhibitors will shed light on the mechanisms underlying regulation of the innate immune response, and provide clues to the development of novel therapeutics for human sepsis.

Lab Members

Wei Li, MD, PhD
Assistant Investigator
Research: Investigating mechanisms underlying regulation of HMGB1 release or cytokine activities.
Phone: (516)-562-1112
E-mail: wli2@northwell.edu

Shu Zhu, MD, PhD
Research Scientist
Research: Investigating innate immune modulatory mechanisms of Chinese herbal medicine.
Phone: (516)-562-2144
E-mail: szhu@northwell.edu

Andrew H. Wu, BS
Visiting Scholar (Medical Student)
Phone: (516)-562-1099
E-mail: hwu2@northwell.edu

Education

Hebei University, P. R. China
Degree: BS
07/1984
Field of Study: Biology

Zhejiang University, P. R. China
Degree: MS
07/1987
Field of Study: Microbiology

Louisiana State University, Baton Rouge, LA
Degree: PhD
12/1992
Field of Study: Microbiology

University of North Carolina at Chapel Hill, NC
Degree: Postdoctoral
10/1995
Field of Study: Cell Biology

Honors and Awards

2003 Ad hoc reviewer, Austrian Science Foundation (Fonds zur Förderung der wissenschaftlichen Forschung, FWF)
2003 Faculty Research Award, Northwell Health Research Institute ($32,000)
2004 Faculty Research Award,Northwell Health Research Institute ($40,000)
2006 Faculty Research Award, The Feinstein Institute for Medical Research ($40,000)
2009 Faculty Research Award, The Feinstein Institute for Medical Research ($50,000)
2009 Mail Reviewer, NIH Special Emphasis Panel, ZRG1 SBIB-V (58) R (7/20/2009)
2009 Mail Reviewer, NIH Special Emphasis Panel, ZRG1 SBIB-V (52) R (8/11/2009)
2009 Member, NIH Special Emphasis Panel, ZRG1 SBIB-D 53 R (11/06/2009)
2010 Faculty Research Award, The Feinstein Institute for Medical Research ($71,000)
2010 Ad hoc reviewer, Science Foundation Ireland (SFI, Wilton Park House, Wilton Place, Dublin 2)
2012 “Peking Union Scholar” Chair Professor, Chinese Academy of Medical Sciences & Peking Union Medical College (¥500,000.00 RMB)
2012 Reviewer, NIH Transformative R01 Roadmap Review, ZRG1 BCMB-A (51)R, RFA RM11-006
2013 Ad hoc Reviewer, NIH/NIGMS, the SAT Study Section (June 5-6, 2013).
2013 Ad hoc Reviewer, NIH/NIGMS, the SAT Study Section (December 9-10, 2013).
2013 Member, NIH/NIDDK ZDK1 GRB-D(J1) Special Review Panel, “Small R03 Grants for New Investigators to Promote Diversity” (December 6, 2013).
2014 Member, NIH/NIGMS ZRG1 F15-P(20)L Fellowship Special Review Panel, Surgical Sciences, Biomedical Imaging and Bioengineering (03/07/2014).
2014 Member, NIH/NIGMS ZRG1 F15-V(05)L Fellowship Special Review Panel, Surgical Sciences, Biomedical Imaging and Bioengineering (03/07/2014).
2014 Ad Hoc Member, the Surgery (SURG) review panel, the U.S. Department of Veterans Affairs (05/21/2014).
2014 Ad Hoc Member, The Surgery (SURG) Review Panel, the U.S. Department of Veterans Affairs (11/19/2014).
2014 Member, NIH/NIGMS ZRG1SBIB V02 Special Emphasis Panel, “Member Conflict: Surgical Sciences and Bioengineering” (BTSS/SAT Study Section Member Conflict Meeting, 10/30/2014).
2015 Member, the Surgery (SURG) review panel, the U.S. Department of Veterans Affairs (05/27/2015).
2015 Ad Hoc Member, the NIH/NIGMS Surgery, Anesthesiology, and Trauma (SAT) Study Section (06/10-11/2015).
2015 Member, NIH/NIGMS ZRG1SBIB Z02 Special Emphasis Panel, “Member Conflict: Surgical Sciences and Bioengineering” (BTSS and SAT Study Section Member Conflict Meeting, 06/30/2015).
2015 Member, NIH/NIGMS ZRG1 F15-P(20) Fellowship Special Review Panel, Surgical Sciences, Biomedical Imaging and Bioengineering (11/06/2015).

Publications

Book Chapters:

  1. Wang, H., A.E. Sama, M.F. Ward, K. Miele, and S. Zhu. 2012. Future Application of Integrative Therapies for Sepsis: Bench and Experimental Animal Models.   In: “Integrative Therapies in Lung Health and Sleep, Respiratory Medicine Series 4″. L. Chlan and M. Hertz, eds. pp189-206. Springer, New York.
  2. Wang, H., S. Zhu, W. Li, A. Jundoria and A.E. Sama. 2012. Tea and Sepsis: Effects on Inflammatory Cytokines. In: “Tea in Health and Disease Prevention.” V.R. Preedy, ed. Academic Press, pp581-591, Oxford.
  3. Wang, H., L. Zhao, J. Li, S. Zhu, and M. Yeung. 2014. Analysis of the released cytokine HMGB1 in human serum. In: “Methods in Molecular Biology: Cytokine Bioassays.” I. Vancurova, ed. Vol. 1172; pp. 13-25, Springer, New York.

Reviews:

  1. Wang, H., M.F. Ward and A.E. Sama. 2014. “Targeting HMGB1 in the treatment of sepsis.” Expert Opinion on Therapeutic Targets 18(3): 257-268.
  2. Lu, B., C. Wang, M. Wang, W. Li, F. Chen, K.J. Tracey, and H. Wang. 2014. “Molecular mechanism and therapeutic modulation of HMGB1 release: an updated review.” Expert Review of Clinical Immunology 10(6): 713-727.
  3. Kang, R., R. Chen, Q. Zhang, W. Hou, S. Wu, L. Cao, J. Huang, X-G. Fan, Z. Yan, X. Sun, Wang, Q. Wang, Al Tsung, T.R. Billiar, H.J. Zeh III, M.T. Lotze, and D. Tang. 2014. “HMGB1 in health and diseases.” Molecular Aspects of Medicine 40: 1-11.
  4. Bao, G., L. He, D. Lee, J. D’Angelo, and #H. Wang. 2015. “An on-going search for potential targets and therapies for sepsis.” Military Med. Res. 2(20): doi:10.1186/s40779-015-0047-0.
  5. Wu, A., L. He, W. Long, P. Qiu, S. Zhu, P. Wang, S. Fan, and #H. Wang. 2015. Novel mechanisms of herbal therapies for inhibiting HMGB1 secretion and action. Evidence-based Complementary and Alternative Medicine Article ID 456305 (11 pages).

Research Articles:

  1. Li, W., S. Zhu, J. Li, A.E. Sama, P. Wang, and H. Wang. 2012. “Use of animal model of sepsis to evaluate novel herbal therapies.” J. Visualized Exp. 62: e3926 (6 pages plus video; DOI: 10.3791/3926).
  2. Lu, B., T. Nakamura, K. Inouye, J. Li, Y. Tang, P. Lundbäck, S. Valdes-Ferrer, P.S. Olofsson, T. Kalb, J. Roth, Y. Zou, H. Erlandsson-Harris, H. Yang, J. P-Y Ting, H. Wang, U. Andersson, D.J. Antoine, S.S. Chavan, G.S. Hotamisligil, & K.J. Tracey. 2012. “Novel role of PKR in inflammasome activation and HMGB1 release.” Nature 488(7413):670-674.
  3. Zhu, S., W. Li, J. Li, A. Jundoria, A.E. Sama & H. Wang. 2012. “It is not just folklore – The aqueous extract of Mung bean coat is protective against sepsis.” Evidence-based Complementary and Alternative Medicine. doi:10.1155/2012/498467 (10 pages).
  4. Zhang, Y., W. Li, S. Zhu, A. Jundoria, J. Li, H. Yang, S. Fan, P. Wang K.J. Tracey, A.E. Sama, and H. Wang. 2012. “Tanshinone IIA sodium sulfonate facilitates endocytic HMGB1 uptake. Biochem.” Pharmacology 84(11):1492-500.
  5. Li, W., J. Li, A.E. Sama, and H. Wang. 2013. “Carbenoxolone blocks endotoxin-induced PKR activation and HMGB1 release.” Mol. Med. 19:203-211.
  6. Zhao, L., W. Li, S. Zhu, S. Tsai, J. Li, K.J. Tracey, P. Wang, S. Fan, A.E. Sama, and #H. Wang. 2013. “Green tea catechins quench the fluorescence of bacteria-conjugated Alexa Fluor Dyes.” Inflamm. Allergy Drug Targets. 12(5): 308-314.
  7. Qiang, X., W-L. Yang, R. Wu, M. Zhou, A. Jacob, W. Dong, M. Kuncewitch, Y. Ji, H. Yang, H. Wang, J. Fujita, J. Nicastro, G.F. Coppa, K.J. Tracey, and P. Wang. 2013. “Release of cold-inducible RNA-binding protein triggers inflammatory responses in hemorrhagic shock and sepsis.”  Nature Medicine 19(11): 1489-1495 (IF = 28.05).
  8. Tang, D., R. Kang, N. E. Schapiro, T. Loux, K.M. Livesey, T.R. Billiar, H. Wang, B. van Houten, M.T. Lotze, and H.J. Zeh. 2014. “The HMGB1/RAGE Inflammatory Pathway Promotes Pancreatic Tumor Growth by Regulating Mitochondrial Bioenergetics.” Oncogene 33: 567-577.
  9. Lu, B., D.J. Antoine , K. Kwan, P. Lundbäck, H. Wähämaa, H. Schierbeck, M. Robinson , M.A. Van Zoelen , H. Yang , J. Li, H. E. Harris, S. S. Chavan, H. Wang, U. Andersson, K. J. Tracey. 2014. “JAK/STAT1 signaling promotes HMGB1 hyperacetylation and nuclear translocation.” Proc. Natl. Acad. Sci. USA 111(8): 3068-3073.
  10. Kang, R., Q. Zhang, W. Hou, Z. Yan, Z., R. Chen, J. Bonaroti, P. Bansal, T.R. Billiar, A. Tsung, Q. Wang, D.L. Bartlett, D.C. Whitcomb, E.B. Chang, X. Zhu, H. Wang, B. Lu, K.J. Tracey, L. Cao, X-G. Fan, M.T. Lotze, M.T., H.J. Zeh III, D. Tang. 2014. “Intracellular HMGB1 inhibits inflammatory nucleosome release and limits acute pancreatitis in mice.” Gastroenterology 146: 1097-1107.
  11. Liu, L., M. Yang, R. Kang, Y. Yu, Y. Dai, F. Gao, H. Wang, X. Sun, X. Li, J. Li, H. Wang, L. Cao, and D. Tang. 2014. “HMGB1-DNA Complex-induced autophagy limits AIM2 Inflammasome activation through RAGE.” Biochem. Biophys. Res. Commun. 450(1):851-856.
  12. Yang, L., M. Xie, M. Yang, Y. Yu, S. Zhu, W, Hou, R. Kang, M. Lotze, T.R. Billiar, H. Wang, L. Cao, and D. Tang. 2014.  “PKM2 Regulates the Warburg Effect and Promotes HMGB1 Release in Sepsis.” Nature Communications 5:4436, doi: 10.1038/ncomms5436.
  13. Yang, H., H. Wang, Z. Ju, A.A. Ragab, P. Lundbäck, W. Long, J.P. Pribis, J. Li, B. Lu, D. Gero, C. Szabo, D.J. Antoine, D.T. Golenbock, J. Meng, J. Roth, S.S. Chavan, U. Andersson, T. Billiar, K.J. Tracey, and Y. Al-Abed. 2015. “MD-2 is required for disulfide HMGB1-dependent TLR4 signaling.” J. Exp. Med. 212(1): 5-14.
  14. Li, W., S. Zhu, J. Li, J. D’Amore, J. D’Angelo, H. Yang, P. Wang, K.J. Tracey, and H. Wang. 2015. “Serum Amyloid A stimulates PKR expression and HMGB1 release possibly through TLR4/RAGE receptors.” Mol. Med. 21: 515-525.
  15. Yang, W-L, A. Sharma, F. Zhang, S. Matsuo, Z. Wang, H. Wang, and P. Wang. 2015. “Milk fat globule epidermal growth factor-factor 8-derived peptide attenuates organ injury and improves survival in sepsis.”  Crit Care 19:375 (13 pages).
  16. Sun, X., Z. Ou, M. Xie, R. Kang, Y. Yu, Y. Fan, X. Niu, H. Wang, L. Cao, D. Tang. 2015. “HSPB1 as a negative regulator of ferroptotic cancer cell death.” Oncogene 34(45):5617-25.
  17. Li, W., A.H. Wu, S. Zhu, J. Li, R. Wu, J. D’Angelo, and #H. Wang. 2015. “EGCG induces G-CSF expression and neutrophilia in experimental sepsis.” Immunol. Res. (in press).

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