East Carolina University, Department of Pharmacology & Toxicology, Brody School of Medicine
“UNDERSTANDING MAST CELL ACTIVATION IN THE DEVELOPMENT OF SAFE NANOTECHNOLOGIES”
Concern about the use of engineered nanomaterials (ENMs) has increased significantly in recent years due to potentially hazardous impacts on human health. Mast cells are critical for innate and adaptive immune responses, often modulating allergic and pathogenic conditions. Mast cells act in response to environmental danger signals such as IL-33 and the IL-1 like receptor ST2. We have examined the involvement of mast cells and the IL-33/ST2 axis in adverse responses to ENMs. Mice with normal mast cell populations exhibit significant ENM directed systemic and pulmonary inflammation, fibrosis, altered lung function and exacerbated cardiac IR injury. In contrast, these toxicological effects of ENMs were not observed in mice deficient in mast cells or mice with mast cells unable to respond to IL-33. Lastly, we have established that certain ENMs are capable of inducing mast cell activation in vitro. Our findings establish for the first time that mast cells orchestrate adverse immune effects to ENMs giving insight into a previously unknown mechanism of toxicity and thereby providing a realistic therapeutic target. Lastly, the use of mast cells and the IL-33/ST2 axis as a screening tool for ENM safety and in the preclinical development of nanomedicines will be presented.
Thursday, October 11, 2012 @ 3:30 PM in Burson 115. Refreshments served at 3:15 PM
Dr. Brown received a Ph.D. in toxicology from the University of Montana with subsequent postdoctoral training in allergy and mast cell biology at the Laboratory of Allergic Disease (NIH, NIAID). Since joining East Carolina University in 2008, he has established a nationally recognized research program in nanotoxicology. He is currently a PI on a NIEHS U19 grant studying the physicochemical properties that influence biological responses to engineered nanomaterials. In addition, he is a PI on an NIEHS RO1 examining the role of mast cells in the adverse health effects of engineered nanomaterials. His laboratory has been active in multiple NIH funded consortiums that are investigating the health and safety of nanomaterials. He is a member of several professional associations including the Society of Toxicology, The American Association of Immunologists and the American Thoracic Society. Dr. Brown has been recognized several times for his outstanding research with awards such as fellows award for research excellence (FARE-NIH, 2006) and the outstanding new environmental scientist award (NIEHS, 2010). Despite his relatively short research career he has already published more than 30 peer-review publications in prestigious journals in the areas of toxicology and nanotechnology.