- Professor, Department of Medicine - Section of Hematology/Oncology; Cancer Research Center; Committee on Cancer Biology; Committee on Genetics, Genomics, and Systems Biology; Committee on Molecular Medicine/MPMM; Committee on Clinical & Translational Science
- Chair, Committee on Clinical Pharmacology and Pharmacogenomics
Ph.D., Purdue, 1983
The University of Chicago
900 East 57th Street
Chicago, Illinois 60637
Phone: (773) 702-4441
Webpage (Cancer Center)
Webpage (Dept. of Medicine)
Pharmacogenomics of Anticancer Agents
Recent advances in genome research have suggested strong associations between genetic factors and complex human traits, such as an individual’s disease susceptibility, response to therapy, and gene expression levels. The objective of our work is to identify genetic determinants contributing to cellular susceptibility to chemotherapeutic agents. Most chemotherapeutic drugs exhibit serious toxicity; hence elucidating the genetic variants that alter their pharmacodynamic effects is an important but challenging project. Challenges include our inability to do family studies evaluating the effects of chemotherapy on individuals without cancer and the multigenic nature of drug response. To this end, I have developed cell-based methods to discover genetic variants contributing to chemotherapeutic-induced cytotoxicity, evaluating the relevance of these variants in a clinical setting, and elucidating the biochemical and cellular impact of the variants. My laboratory was the first to demonstrate that chemotherapeutic-induced cytotoxicity is a heritable trait. Our approach integrates multiple large datasets including: genetic variation, gene expression, miRNA, modified cytosine, transcription factor levels and chemotherapeutic induced pharmacologic traits (cytotoxicity, apoptosis) in the same set of cell lines from different world populations. We made the observation that pharmacologic SNPs, identified through genome wide association studies, are enriched in expression quantitative trait loci (eQTL) and more recently, in protein quantitative trait (pQTL) loci. Recently, we have focused on identifying genetic variants associated with chemotherapeutic induced sensory peripheral neuropathy. We are developing genetically diverse neuronal cells using induced pluripotent cell derived from blood or lymphoblastoid cell lines to evaluate the effect of different neurotoxic chemotherapeutics (paclitaxel, cisplatin, vincristine, oxaliplatin). We are studying how different phenotypic characteristics in cell based models represent different clinical manifestations of neuropathy. We use human neurons to evaluate genes contributing to neuropathy using an siRNA screen. The model we are developing will have broad applicability for testing neurotoxic agents and identifying relevant targets for new drugs to prevent neuropathy.
I am Chair of the Committee on Clinical Pharmacology and Pharmacogenomics, a board-certified training program for clinical and post-doctoral fellows. I have been co-leader of the UCCCC Pharmacogenomics and Experimental Therapeutics Program since 2000. I have mentored clinical fellows, post-doctoral fellows, graduate students, medical students, undergraduate students, a high school teacher and many high school students.