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Peter Dornbos

Peter DornbosCooperating Doctoral Program: Biochemistry & Molecular Biology

EITS Track: Biomedical Toxicology

Education: B.S. Biology, Calvin College

Research Interests:
My thesis project work is primarily focused on the effects of genetic variability on dose-response curves. Recently, the National Research Council (NRC) hypothesized that the traditional nonlinear dose-response curve for non-cancer endpoints will linearize when the genetic variability of a population is taken into consideration. This hypothesis has not been adequately tested. The purpose of this project is to generate preliminary data to address this knowledge gap by determining the shape of the dose response curve while accounting for genetic variability. We hypothesize that incorporation of population variability will not linearize the dose-response curve as suggested by the NRC. In testing our hypothesis, 2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD) will be used as test chemical. First, CD40L-activated B cells from fifty unique human donors will be dosed with increasing levels of TCDD in vitro; statistical models will be used to assess whether the response is best fit with a linear or nonlinear model. The hypothesis will be further tested using the Mouse Phenome Panel which has the genetic power to model the variability within the human population. Several endpoints from the mouse model, including serum hormone levels, genome-wide gene expression, and embryotoxicity, will be modeled computationally to assess whether the simulated genetic variability of the population linearizes the dose-response relationships. Results from the proposed studies are likely to have direct implications in population-level risk assessment of not only TCDD, but other non-cancer causing chemicals and pharmaceuticals as well.

Major Professor: John LaPres, Biochemistry & Molecular Biology