Laboratory of Emergency Medicine
Haichao Wang, PhD Associate Investigator |
The mission of the Laboratory of Emergency Medicine is to conduct research into 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, Dr. Wang and his colleagues 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.
Severe sepsis is an overwhelming systemic inflammatory response to infection, claiming approximately 225,000 victims annually in the U.S. alone. The high mortality of sepsis is in part mediated by dysregulated inflammatory responses manifested by excessive accumulation of pro-inflammatory cytokines. Using rodent models of endotoxemia and sepsis (induced by cecal ligation and puncture), we discovered a ubiquitous nucleosomal protein, HMGB1, as a critical late-acting proinflammatory mediator for lethal systemic inflammatory diseases (Science 1999, 285: 248-251).
Dr. Wang's groundbreaking studies on HMGB1 are acclaimed for furthering the academic knowledge surrounding immunology and inflammation management to alleviate disease propagation. We are currently investigating the mechanisms underlying regulation of HMGB1 release in animal models of experimental sepsis, and uncovering intricate mechanisms by which several herbal-derived agents (EGCG and tanshinones) inhibits HMGB1 release and/or action. 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.
Developing ways to therapeutically treat and slow and reverse the progression of sepsis is 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.
Lab Members:
Name: Mala Ashok, MD
Position: Research Associate
Research: Establishing animal models of inflammatory diseases (sepsis and arthritis).
E-mail: mashok@nshs.edu
Name: Shu Zhu, MD, PhD
Position: Research Scientist
Research: Investigating innate immune modulatory mechanisms of Chinese herbal medicine.
E-mail: sshu@nshs.edu
Name: Wei Li, MD, PhD
Position: Research Scientist
Research: Investigating mechanisms underlying regulation of HMGB1 release or cytokine activities.
E-mail: wli2@nshs.edu
Name: Ben Lu, MD
Position: Visiting Student from Xiangya Hospital, Central South University, China
Research: Working on HMGB1-related research project that focuses on understanding of mechanisms underlying regulation of HMGB1 release in macrophage/monocyte.
Publications:
Li, W., J., Li, M. Ashok, R. Wu, D. Chen, L. Yang, H. Yang, K.J. Tracey, P. Wang, A.E. Sama, and H. Wang. (2007). A cardiovascular drug rescues mice from lethal sepsis by attenuating late-acting proinflammatory mediator, HMGB1. Journal of Immunology 178(6): 3856-3864.
Ivanov, S., A-M, Dragoi, D.V. Essen, J. Louten, G. Yap, Y. Wan, C.A. Biron, M.E. Bianchi, H. Wang, and W-M. Chu. (2007). A novel role for HMGB1 in TLR9-mediated inflammatory responses to CpG-DNA. Blood 110(6): 1970-1981.
Li, W., M. Ashok, J., Li, H. Yang, A.E. Sama, and H. Wang. (2007). A major ingredient of green tea rescues mice from lethal sepsis partly by inhibiting HMGB1. PLoS ONE 2(11): e1153.
Tang D., R. Kang, L. Cao, G. Zhang, Y. Yu, W. Xiao, H. Wang, and X. Xiao. (2008). A pilot study to detect HMGB1 and HSP72 in cerebrospinal fluid of pediatric patients with meningitis. Critical Care Medicine 36(1):291-295.
Wang, H., S. Zhu, R. Zhou, W. Li, & A.E. Sama (2008). Therapeutic potential of HMGB1-targeting agents in sepsis. Expert Reviews in Molecular Medicine 10: e32 (1-20).
Wang, H., S. Zhu, M.F. Ward, J. Gong, & A.E. Sama (2008). Hyperglycemia aggravates endotoxin-induced HMGB1 release: yet another reason not to be too sweet. Critical Care Medicine 36(8): 2475-2476.