School of Pharmacy
Area of interest
A central goal of cancer pharmacogenomics is the prediction of drug toxicity based on a patient?s genetic profile, preferably assayed using a widely available and inexpensive genetic test that can be performed on an easily obtainable biological sample, such as peripheral blood. However, many of the reported examples in the cancer harmacogenomics literature are confounded by a lack of statistical power and a paucity of biological plausibility. Furthermore, while single-gene pharmacogenetic studies of highly penetrant genes are promising, response and toxicity to most chemotherapy agents are likely complex multigenic traits representing a complex interplay among multiple polymorphic genes and environmental factors. Genetic mapping studies of complex, multigenic traits like drug response in humans are difficult to conduct and require identification of relevant patient populations for both discovery and replication. This introduces further practical issues, as the sample size required to uncover a region of interest from a genome-wide scan of unrelated individuals is far beyond that normally encountered in human clinical trials. Consequently, in order to more fully understand the genetic basis of drug response, preclinical genome-wide approaches devoid of a priori assumptions are needed to gain broader knowledge of the genetic basis of chemotherapy. I have focused on using mouse models to further these goals.