CEEH Facility Core #2: Biomarkers and Metabolomics Development

Genomics and proteomics have contributed much to our basic understanding of toxicology, but have not provided all the information necessary to understand mechanisms of toxicity, or diversity in toxicological response to environmental exposures.  A promising new technology is that of ‘metabolomics’, which refers to the “systematic study of the small-molecule metabolite profiles that result from exogenous stimuli, including exposure to environmental toxicants"*. The emerging field of metabolomics offers great promise for the development of early biomarkers of toxin exposure, and of disease resulting from those exposures.

The terms “metabolomics” and “metabonomics” were coined in the 1990’s to describe a field of investigation distinct from genomics and proteomics in that the molecules under study are “downstream” from the original endogenous and exogenous stimuli producing changes in gene expression.

The CEEH is currently in the process of establishing a new Biomarkers and Metabolomics Development Core which will provide a collaborative resource for assessing global metabolite profiles and targeted metabolite analyses from various biological and environmental samples. This facility core will develop and implement a coordinated workflow that facilitates utilization of metabolomic fingerprinting or profiling as a biomarker of exposure and environmentally-induced disease. In addition, the core will promote translation of these biomarkers into clinical use through development of sensitive and specific quantitative analysis techniques based on mass spectrometry.

Proposed Projects:

• Identification of plasma and urine biomarker profiles that reflect CYP3A activity following treatment with sulforaphane and rifampin. Using metabolomic profiling technologies to measure endogenous we will  be able to measure compounds that reflect cytochrome P450 3A (CYP3A) activity. CYP3A is responsible for the biotransformation of many drugs, pesticides, carcinogens and other endogenous and exogenous chemicals.
   
• Acetominophen Toxicity in Cell Culture and Mouse Models. Metabolomic profiling technologies will be used to determine whether in vitro and in vivo markers of acetominophen toxicity are comparable.   This involves comparing the intracellular fluid and media of mouse hepatocytes treated with acetaminophen to serum drawn from mice treated with acetaminophen.
   
• Pesticide exposure in children. Metabolomic profiling technologies will allow CEEH researchers to ascertain the association between organophosphorus pesticide exposure and steroid metabolism.

• Access to technology services (i.e. microarray, specimen analysis)
• Consultations (i.e. study design, experiment design)