Laboratory of Surgical Research
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).