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Appointments:
Professor
Department of Medicine
Section of
Hematology/Oncology
Cancer Research Center
Chair, Committee on Clinical Pharmacology and Pharmacogenomics
Committee on Cancer Biology
Committee on Genetics
Committee on Molecular Medicine/MPMM
Committee of Clinical & Translational Science
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Education:
Ph.D., Purdue, 1983
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Contact:
Phone: (773) 702-4441
Fax:
(773) 702-9268
E-Mail: edolan@medicine.bsd.uchicago.edu
Address:
The University of Chicago
KCBD 7100
900 East 57th Street
Chicago, Illinois 60637
Webpage (Cancer Center)
Webpage (Dept. of Medicine)
Webpage (IGSB)
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Related Research Interests:
Chromosome
Damage/Repair
DNA Repair
Drug
Resistance/Toxicology
Pharmacogenetics
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M. Eileen Dolan, Ph.D.
Pharmacogenomics of Anticancer Agents
Research Summary
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. Therefore, we have
developed
several cell based models to identify genetic variants important in
chemotherapeutic-induced toxicity. The models employ EBV-transformed
lymphoblastoid cell lines from related healthy Caucasians of European
descent
(CEPH) and Yorubans of African descent to evaluate
chemotherapeutic-induced
cytotoxicity and/or apoptosis. These family-based cell lines allow us to apply familial genetic strategies
to determine
the heritability and the genetic components contributing to complex
phenotypes
such as susceptibility to chemotherapy. The pedigrees have
microsatellite and
SNP data available for linkage mapping studies. Furthermore, the HapMap
trios
contained within these large pedigrees have over 3 million SNPs
genotyped. We
have performed expression array to allow for studies of population
differences
in gene expression and cellular susceptibility to chemotherapy. Our laboratory was the first to demonstrate
susceptibility to chemotherapy-induced cytotoxicity is significantly
heritable
and that susceptibility to chemotherapeutic toxicity in Caucasians and
Africans
is significantly different for certain drugs. Our long-term goal is to
identify
genetic variants and gene expression, including those in an underserved
population that predict risk for adverse reactions to chemotherapeutic
agents.
Selected Papers
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
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
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
Duan, S., Huang, R.S., Zhang, W., Bleibel, W.K., Roe, C.A., Clark, T.A., Chen, T.X., Schweitzer, A.C., Blume, J.E., Cox, N.J., and Dolan, M.E. Genetic Architecture of Transcript-Level Variation in Humans, Amer. J. Human Genetics, 82:1101-1113, 2008. PMID18439551 PMCID: PMC2651622
Huang, R.S., Duan. S, Kistner, E.O., Hartford, C.M., Dolan, M.E. Genetic variants associated with carboplatin-induced cytotoxicity in cell lines derived from Africans, Molec Cancer Ther., 7(9): 3038-3046, 2008. PMID18765826
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
O’Donnell, P.H. and Dolan, M.E. Cancer Pharmacoethnicity: Ethnic Differences in Susceptibility to the Effects of Chemotherapy. Clin Cancer Res, 15:4806-14, 2009 PMID: 19622575 PMCID: PMC2774468
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
Gamazon E.R., Huang R.S., Cox N.J., Dolan, M.E. Chemotherapeutic Drug Susceptibility Associated SNPs are Enriched in Expression Quantitative Trait Loci, PNAS, 107, 9287-9292, 2010. PMID: 20442332 PMCID: PMC2889115
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Faculty and Research
Programs
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