Distribution of PCB Atropisomers

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DESCRIPTION (provided by applicant): The immediate objective of this Mentored Research Scientist Award is to allow Dr. Hans-Joachim Lehmler to make a successful transition to an independent investigator in the field of environmental toxicology. In the research component of this award, Dr. Lehmler will test the working hypothesis is that chiral environmental contaminants such as PCB 84 are enantioselectively metabolized by cytochrome P450, resulting in a selective enrichment of one enantiomer of PCB 84 in certain tissues. Alternatively, the enrichment of one PCB 84 enantiomer resulting from differential transport of PCB enantiomers by plasma proteins will be investigated. The specific aims are (1) to determine the enantioselectivity of the in vitro metabolism of PCB 84, (2) to study the binding of both PCB 84 enantiomers to mice and human serum proteins, and (3) to determine the distribution and disposition of PCB 84 enantiomers in female mice and the transfer of the enantiomers into the fetus and suckling offspring. This research component will be complemented by a vigorous career development plan which will include (1) formal training in biostatistics and the ethical conduct of research as part of the curriculum of the NIEHS training grant in the Department of Occupational and Environmental Health, (2) regular meetings with his mentors, collaborators and consultants, (3) participation in group meetings and departmental seminars, (4) presenting results at scientific meetings such as the PCB Workshop and (5) publishing in peer reviewed journals. It is envisioned that the multidisciplinary team of mentors, collaborators and consultants plays an active role in both the research as well as the career development component of this award. The long term career goal is to establish Dr. Lehmler as an investigator with independent research status and funding.