Laboratory of Surgical Research
Ping Wang, MD |
Ideas are the currency in the laboratory of Dr. Wang. He was introduced to severe sepsis during his medical training in China. He became a surgeon, and learned early on that post-surgical infections are common and can be deadly.
It was clear early in Dr. Wang’s surgical career that he wanted to discover medicines that would prevent the inflammatory cascade in severe sepsis. He has identified peptides and proteins that can improve cardiovascular responses and organ function and has conducted a series of pre-clinical studies showing that they enhance survival. The peptide, adrenomedullin (AM), in combination with its binding protein AMBP-1, suppresses inflammation and could ultimately prove a powerful treatment for sepsis. AM and AMBP-1 are also effective in treating trauma and hemorrhage in laboratory models. Cell death is also a major focus of his research. Apoptosis is a two-way street. Normally, the body’s immune system has a good mechanism to get rid of dead cells, sending in white blood cells called macrophages to digest and clear away the cellular debris. Working in the lab, he discovered a protein, MFG-E8, which enhances clearance of these dead cells and could prove a powerful model in developing ways to counteract this process. They showed in a test tube and in experimental models that giving MFG-E8 back to cells undergoing apoptosis, enhanced phagocytosis and limited secondary necrosis and inflammation.
The sympathetic nervous system releases norepinephrine and too much can trigger the production of cytokines. He also recently discovered that the alpha2A adrenergic receptor mediates the detrimental effects of norepinephrine. He describes himself as a “mediator junkie,” and has become interested in the aging process. The inflammatory response is 50 to 100 times higher in laboratory models of aging and this can easily shift the balance between a fatal and nonfatal response to infection. He is now testing the benefits of ghrelin and growth hormone in suppressing the inflammatory response in laboratory models.
They are in the process of identifying new therapeutic approaches to reduce sepsis-induced lethality in the geriatric population. They also discovered that the peptide ghrelin reduces inflammation, attenuates organ injury and reduces mortality in models of sepsis, and now they are testing the potent anti-inflammatory peptide in models of radiation damage and sepsis (radiation combined injury).
Lab Members:
Position: Research Scientist
Research: Molecular basis of inflammation.
E-mail: avarghes@nshs.edu
Name: Derry Rajan, MD
Position: Postdoctoral Research Fellow
Research: Novel pro-inflammatory mediators and sepsis.
E-mail: kshah@nshs.edu
Name: Hidefumi Komura, MD, PhD
Position: Postdoctoral Research Fellow
Research: MFG-E8, apoptosis, and phagocytosis.
E-mail: hkomora@nshs.edu
Name: Kavin G. Shah, MD
Position: Postdoctoral Research Fellow
Research: Combined radiation injury.
E-mail: kshah@nshs.edu
Name: Wayne Chaung, PhD
Position: Research Scientist
Research: Mediators and organ injury.
E-mail: wchaung@nshs.edu
Name: Xiaoling Qiang, MD, PhD
Position: Research Scientist
Research: Novel pro-inflammatory mediators.
E-mail: xqiang@nshs.edu
Name: Fangming Zhang, MD, PhD
Position: Research Associate
Research: Sepsis and other inflammatory diseases.
E-mail: fzhang1@nshs.edu
Name: Mian Zhou, MD
Position: Senior Research Scientist
Research: Sepsis, hemorrhage, and ischemia/reperfusion injury.
E-mail: mzhou@nshs.edu
Name: Ronggian Wu, MD, PhD
Position: Senior Research Scientist / Assistant Professor
Research: Sepsis, hemorrhage, and ischemia/reperfusion injury.
E-mail: rwu@nshs.edu
Name: Weifeng (David) Dong, MS
Position: Senior Research Assistant
Research: Experimental studies on inflammation.
E-mail: wdong@nshs.edu
Name: Youxin Ji, MD
Position: Senior Research Assistant
Research: Experimental studies on inflammation.
E-mail: yji@nshs.edu
Name: Zhimin (Wendy) Wang, MD
Position: Research Associate
Research: Experimental studies on inflammation.
E-mail: zwang@nshs.edu
Name: Madeline Ann Quinn
Position: Administrative Supervisor
Research: Laboratory management
E-mail: maquinn@nshs.edu
Phone: (516) 562-3411
Selected Publications:
Miksa M, Wu R, Cui X, Dong W, Das P, Simms HH, Ravikumar TS, Wang P: Vasoactive hormone adrenomedullin and its binding protein after injury: anti-inflammatory effects by up-regulating peroxisome proliferators-activated receptor-gamma. J Immunol 179:6263-6272, 2007.
Wu R, Dong W, Zhou M, Zhang F, Marini CP, Ravikumar TS, Wang P: Ghrelin attenuates sepsis-induced acute lung injury and mortality in rats. Am J Respir Crit Care Med 176:805-813, 2007.
Jacob A, Zhou M, Wu R, Halpern VJ, Ravikumar TS, Wang P: Proinflammatory cytokines from Kupffer cells downregulate hepatocyte expression of adrenomedullin binding protein-1. Biochim Biophys Acta 1772:766-772, 2007.
Wu R, Dong W, Cui X, Zhou M, Simms HH, Ravikumar TS, Wang P: Ghrelin downregulates pro-inflammatory cytokines in sepsis via activation of the vagus nerve. Ann Surg 245:480-486, 2007.
Dwivedi AJ, Wu R, Nguyen E, Higuchi S, Wang H, Krishnasastry K, Marini CP, Ravikumar TS, Wang P: Adrenomedullin and adrenomedullin binding protein-1 prevent acute lung injury after gut ischemia- reperfusion. J Am Coll Surg 205:284-293, 2007.
Wu R, Dong W, Zhou M, Simms HH, Marini CP, Ravikumar TS, Wang P: Adrenomedullin and adrenomedullin binding protein-1 prevent metabolic acidosis after uncontrolled hemorrhage in rats. Crit Care Med 35:912-918, 2007.
Miksa M, Amin D, Wu R, Dong W, Ravikumar TS, Wang P: Fractalkine-induced MFG-E8 leads to enhanced apoptotic cell clearance by macrophages. Mol Med 13:553-560, 2007.
Wu R, Zhou M, Das P, Dong W, Ji Y, Yang D, Miksa M, Zhang F, Ravikumar TS, Wang P: Ghrelin inhibits sympathetic nervous activity in sepsis. Am J Physiol Endocrinol Metab 293:E1697-E1702, 2007.
Zhou M, Wu R, Dong W, Jacob A, Wang P: Endotoxin downregulates peroxisome proliferator-activated receptor-gamma via the increase in TNF-alpha release. Am J Physiol Regul Integr Comp Physiol 294:R84-R92, 2008.
Wu R, Dong W, Ji Y, Zhou M, Marini CP, Ravikumar TS, Wang P: Orexigenic hormone ghrelin attenuates local and remote organ injury after intestinal ischemia-reperfusion. PloS ONE 3(4):e2026, 2008 (8 pages).
Zhou M, Jacob A, Ho N, Miksa M, Wu R, Maitra SR, Wang P: Downregulation of protein disulfide isomerase in sepsis and its role in tumor necrosis factor-alpha release. Crit Care 12:R100, 2008 (8 pages).
Qiang X, Wu R, Ji Y, Zhou M, Wang P: Purification and characterization of human adrenomedullin binding protein-1. Mol Med 14:443-450, 2008.
Xu J, Kim HT, Ma Y, Zhao L, Zhai L, Kokorina N, Wang P, Messina JL: Trauma and hemorrhage-induced acute hepatic insulin resistance: dominant role of tumor necrosis factor-α. Endocrinology 149:2369-2382, 2008.
Zhang F, Wu R, Zhou M, Blau SA, Wang P: Human adrenomedullin combined with human adrenome-dullin binding protein-1 is protective in gut ischemia and reperfusion in the rat. Regul Peptides 152:82-87, 2009.
Miksa M, Komura H, Wu R, Shah KG, Wang P: A novel method to determine the engulfment of apoptotic cells by macrophages using pHrodo succinimidyl ester. J Immunol Methods 342:71-77, 2009.
Yang J, Wu R, Qiang X, Zhou M, Dong W, Ji Y, Marini CP, Ravikumar TS, Wang P: Adrenomedullin and its binding protein attenuate organ injury and reduce mortality after hepatic ischemia-reperfusion. Ann Surg 249:310-317, 2009.
Komura H, Miksa M, Wu R, Goyert SM, Wang P: Milk fat globule epidermal growth factor-factor VIII is down-regulated in sepsis via the lipopolysaccharide-CD14 pathway (Feature Article). J Immunol 182:581-587, 2009.
Wu R, Zhou M, Dong W, Ji Y, Miksa M, Marini CP, Ravikumar TS, Wang P: Ghrelin hyporesponsiveness contributes to aging-induced hyperinflammation in septic shock. Ann Surg 2009 (in press).