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Michigan State University

Superfund Research Program

Environmental, Microbial, and Mammalian Biomolecular Responses to AhR Ligands

Center Director: Norbert E. Kaminski
Grant Number: P42ES004911
Funding Period: 1989-2027
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Summary (2013-2021)

The Michigan State University Superfund Research Program (MSU SRP), which began in 1988, is continuing research directed toward understanding and alleviating the adverse impacts of human health from exposure to chemicals commonly found at Superfund sites. The central overarching theme of the Program is to define specific aspects of environmental, microbial and mammalian bimolecular responses to environmental contaminants that act as ligands for the aryl hydrocarbon receptor (AhR).

The specific agents that are studied are a subset of chemicals belonging to the halogenated aromatic hydrocarbon (HAH) family. Of the HAHs contaminating the environment, the most toxic are these that act as AhR ligands. The most potent and highest affinity AhR agonist is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin), which is being studied in all of the projects and represents one of many unifying aspects of the new Program. Likewise, the focus of all of the projects and overall objective of the Program is to define mechanistically, quantitatively and computationally the interactions of AhR ligands with biotic and abiotic processes that ultimately determine the environmental fate and toxicity of these contaminants.

Specific emphasis is placed on two major areas of research within the central theme:

  1. Characterizing specific biological, physical and chemical criteria governing the environmental fate of AhR ligands
  2. Developing statistical and computational models from mechanistic research that describe interactions between the ligand-activated AhR and the biochemical and molecular events controlling cellular responses.

The quantitative/computational techniques and approaches used in the majority of the research projects reflect a "state-of-the-art" systems approach to understanding complex biological systems. These areas of research represent a logical evolution of research direction for this Superfund Center.

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