(SELECTED)2010 STEER Projects
“Molecular Mechanisms of Wood Smoke-Induced Alterations in Macrophage Functions”
Dr. Christopher Migliaccio and Dr. Tony Ward
Exposure to wood smoke particulate matter (WS-PM) can be from either periodic or chronic exposures. Epidemiological data has shown a link between exposures to biomass smoke and increased incidence in respiratory infections. Recent data in our laboratory has shown an increase in bacterial deposition in WS-exposed mice. The main immune cell of the alveolar spaces, the alveolar macrophage, is key to responses to inhaled particles and antimicrobial immunity. Both WS inhalation and WS-PM instillation studies have resulted in the activation of the non-canonical NFkB member, RelB. RelB has been associated with a PAH induced decreases in macrophage functions in other systems. The present study proposes to assess changes to macrophages following exposure to wood smoke particles with respect to RelB activation. The results of these studies will elucidate the mechanism of an increased susceptibility to respiratory infection following exposure to wood smoke.
In this project, the student will learn animal exposure models, flow cytometry, immunohistochemistry, and sterile techniques, including tissue culture of primary cells.
“Regulation of inflammation and immunity by the Aryl hydrocarbon receptor”
Dr. David Shepherd
The Aryl hydrocarbon receptor (AhR) functions as a ligand-activated transcription factor that is differentially expressed in many cells of the immune system. The AhR binds to many pollutants such as dioxins and PCBs that contaminate the global environment and have been linked to many adverse effects on humans such as cancer and chronic inflammatory diseases. Recently, a novel role for the AhR has been discovered that indicates that this cytosolic receptor plays an integral role in regulating the immune and inflammatory responses by macrophages and dendritic cells. Because both of these immune cell populations contribute to the generation and regulation of both innate and adaptive immune responses, it is critical to understand how the AhR functions in them. To this end, we are studying the effects of AhR activation in both macrophages (Macs) and dendritic cells (DCs) by in vitro cell culture approaches as well as in vivo animal modeling. The goals of these studies are to define the consequences of AhR activation on inflammation and immunity and on diseases such as colitis and silicosis that can be significantly affected by environmental pollutants.
This summer project will provide the student researcher with an opportunity to learn both the theory and techniques behind the immunotoxic effects of environmental pollutants. It will also give the student hands-on experience related to the design and execution of novel experiments intended to discover how the AhR regulates immune and inflammatory responses. Technically, you will learn how to culture bone marrow cells into primary cultures of Macs and DCs as well as transformed macrophage and dendritic cell lines. You will learn cutting-edge techniques such as flow cytometry and real-time RT-PCR and apply those to defining the role of the AhR. In addition, you will be exposed to ongoing animal experiments to evaluate the effects of environmental pollutants on chronic inflammatory diseases in the gut and lungs. Collectively, it is expected that the student will not only learn how to set up and perform biomedical research but will also generate novel data that will improve our understanding of environmentally-induced diseases.
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