Eileen Dolan
Section of Hematology / Oncology
Professor of Medicine

Training

DegreeYearInstitutionArea
BS1979University of DaytonChemistry
PhD1983Purdue UniversityMedicinal Chemistry
Fellowship1986The Milton S. Hershey Medical CenterBiochemistry

Academic Interests

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 drugs and gene expression levels. Most chemotherapeutic drugs exhibit serious toxicity; hence elucidating the genetic variants that alter response to chemotherapy and/or toxicity 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. Our research program focuses on determining the genetic variants responsible for inter-individual and inter-ethnic differences in response to chemotherapy using lymphoblastoid cell lines derived from individuals collected for the International HapMap Project. The long-term goal is to identify patients at risk for non response or toxicity associated with chemotherapy. We have developed several cell-based models that employ EBV-transformed lymphoblastoid cell lines from Caucasians of European descent (CEU); Yorubans of African descent (YRI); Japanese in Tokyo, Japan; Han Chinese in Beijing, China; Chinese in metropolitan Denver, CO, USA; African ancestry in the Southwest USA; and Mexican ancestry in Los Angeles, CA, USA to evaluate chemotherapeutic-induced cytotoxicity and/or apoptosis. Our laboratory was the first to demonstrate that chemotherapeutic induced cytotoxicity is a heritable trait. We systematically evaluated SNPs associated with chemotherapeutic-induced cytotoxicity for various chemotherapeutic agents and found that these pharmacogenomic markers are disproportionately likely to be expression quantitative trait loci (eQTLs, indicating that a SNP genotype is associated with the transcript abundance level of a gene). We developed a “triangle approach” to identify genetic variants associated with chemotherapeutic-induced cytotoxicity that are also associated with gene expression and whose target genes’ baseline expression significantly correlate to drug cytotoxicity. We have numerous clinical trials aimed at testing these SNPs as pharmacogenomic markers for patient response and/or toxicity to chemotherapy.


Representative Publications

  1. Huang, R.S., Duan, S., Shukla, S.J., Kistner, E.O., Clark, T.A., Chen, T.X., Schweitzer, A.C., Blume, J.E., Dolan, M.E. Identification of genetic variants contributing to Cisplatin-induced cytotoxicity using a genome-wide approach. Amer. J. Human Gen., 81(3):427-37. 2007 PMID17701890 PMCID: PMC1950832
  2. Duan, S., Bleibel, W.K., Huang, S.R., Shukla, S.J., Wu, X., Badner, J.A., Dolan, M.E. Mapping genes that contribute to Daunorubicin-induced cytotoxicity. Cancer Res., 67(11):5425-5433, 2007. PMID17545624
  3. Zhang, W., Duan, S., Kistner, E. O., Bleibel, W. K., Huang, R. S., Clark, T. A., Chen, T. X., Schweitzer, A.C., Blume, J. E., Cox, N. J. and Dolan, M. E. Evaluation of Genetic Variation Contributing to Differences in Gene Expression Between Populations. Amer. J. Human Genetics, 82: 631-640, 2008. PMID18313023 PMCID: PMC2427223
  4. Welsh M., Mangravite L., Medina M., Tantisira K., Zhang, W., Huang R. S., McLeod H., Dolan M. E. Pharmacogenomic Discovery Using Cell-Based Models. Pharmacological Reviews. 61:413-429, 2009. PMID: 20038569 PMCID: PMC2802425
  5. Hartford CM, Duan S, Delaney SM, Mi S, Kistner EO, Lamba JK, Huang RS, Dolan ME. Population specific genetic variants important in susceptibility to cytarabine arabinoside cytotoxicity. Blood 10:2145-2153, 2009. PMID19109566 PMCID: PMC2652364



More Information

For more information about Dr. Eileen Dolan publications and research collaborations , please click here