Redox-Mediated Events in Modulation of Lung Infection Susceptibility by Engineered Nanomaterials
Brian Thrall, Ph.D.
Technical Group Leader for the Cell Biology Group
Pacific Northwest National Laboratory
Richland, WA
January 25th, 2018
1:00-2:00 pm
665 Huntington Ave,
Bldg. 1, Room 1302,
Boston, MA, 02115
Abstract: While the potential adverse health impacts of ENMs in humans remain uncertain, epidemiological studies link exposure to nanoscale particulates from ambient and occupational sources with increased morbidity and susceptibility to lung infections, including pneumonia. Studies have demonstrated that prior exposure to ENMs can dysregulate macrophage gene regulation, resulting in diminished phagocytic activity toward Streptococcus pneumonia and other bacterial pathogens. Our structure-activity studies further predict that the potency by which ENMs suppress phagocyte function and exacerbate infections in animal models is related to the ease in which they promote cellular redox stress. Advances in quantitative, redox proteomics and transcriptional profiling technologies now make it feasible to identify the precise sites of cellular protein redox modifications caused by ENM exposure. We are using these strategies within NHIR consortium to identify the early molecular targets of redox stress caused by nanomaterials, and understand how these redox modifications translate to altered biological function. Identifying these early molecular initiating events with engineered particles will not only advance predictive hazard capability that can help guide safe nanotechnology development, but will provide important new insights into the fundamental mechanisms of susceptibility associated with ambient particulate matter exposures. (Supported by NIEHS Grants ES019544 and ES027292).
Biographical Sketch: Dr. Thrall is Associate Director and Chief Scientist for Biomedical Science of the Biological Sciences Division at Pacific Northwest National Laboratory (PNNL). He received his Ph.D. in Pharmacology and Toxicology from Washington State University, and has over two decades experience leading multidisciplinary research programs focused on understanding and prediction of human health impacts of environmental exposures, using comprehensive multi-‘omics, imaging and computational biology strategies. He has served as Director of PNNL’s NIEHS U19 Center for Nanotoxicology, and currently leads PNNL research programs supported by the NIEHS Nanotechnology Health Implications Research (NHIR) Consortium. Dr. Thrall has also served on a numerous national advisory and review panels for NIH, EPA, DOE, NIOSH, the National Academy of Science, National Nanotechnology Initiative, and as Chair of the NIEHS NHIR Consortium Steering Committee.
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