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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
5K25ES012475-04
Application #
7267652
Study Section
Special Emphasis Panel (ZES1-LKB-E (HL))
Program Officer
Shreffler, Carol K
Project Start
2004-09-03
Project End
2009-07-31
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
4
Fiscal Year
2007
Total Cost
$128,733
Indirect Cost
Name
University of Iowa
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
P?n?íková, Kate?ina; Brenerová, Petra; Svržková, Lucie et al. (2018) Atropisomers of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) exhibit stereoselective effects on activation of nuclear receptors in vitro. Environ Sci Pollut Res Int 25:16411-16419
Kania-Korwel, Izabela; Lehmler, Hans-Joachim (2016) Chiral polychlorinated biphenyls: absorption, metabolism and excretion--a review. Environ Sci Pollut Res Int 23:2042-57
Kania-Korwel, Izabela; Lehmler, Hans-Joachim (2016) Toxicokinetics of chiral polychlorinated biphenyls across different species--a review. Environ Sci Pollut Res Int 23:2058-80
Kania-Korwel, Izabela; El-Komy, Mohammed H M E; Veng-Pedersen, Peter et al. (2010) Clearance of polychlorinated biphenyl atropisomers is enantioselective in female C57Bl/6 mice. Environ Sci Technol 44:2828-35
Lehmler, Hans-Joachim; Harrad, Stuart J; Huhnerfuss, Heinrich et al. (2010) Chiral polychlorinated biphenyl transport, metabolism, and distribution: a review. Environ Sci Technol 44:2757-66
Li, Xueshu; Parkin, Sean; Duffel, Michael W et al. (2010) Biphenyl-4-yl 2,2,2-trichloro-ethyl sulfate. Acta Crystallogr Sect E Struct Rep Online 66:o1073
Xie, Wei; Bothun, Geoffrey D; Lehmler, Hans-Joachim (2010) Partitioning of perfluorooctanoate into phosphatidylcholine bilayers is chain length-independent. Chem Phys Lipids 163:300-8
Telu, Sanjay; Parkin, Sean; Robertson, Larry W et al. (2010) Improved syntheses of non-dioxin-like polychlorinated biphenyls (PCBs) and some of their sulfur-containing metabolites. Environ Int 36:828-34
Ojogun, Vivian; Vyas, Sandhya M; Lehmler, Hans-Joachim et al. (2010) Partitioning of homologous nicotinic acid ester prodrugs (nicotinates) into dipalmitoylphosphatidylcholine (DPPC) membrane bilayers. Colloids Surf B Biointerfaces 78:75-84
Milanowski, Bart?omiej; Lulek, Janina; Lehmler, Hans-Joachim et al. (2010) Assessment of the disposition of chiral polychlorinated biphenyls in female mdr 1a/b knockout versus wild-type mice using multivariate analyses. Environ Int 36:884-92

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