M. Eileen Dolan, PhD
Pharmacogenomics researchers study the role of genomic variation in drug response with the goal to personalize pharmacological treatment strategies that maximize the potential for therapeutic benefit, while minimizing the risk of toxicity. The Department of Medicine has led groundbreaking studies ranging from discovery of genetic variants associated with drug response to clinical implementation of variants that impact patient care. Studies conducted by M. Eileen Dolan, PhD, have been instrumental in identifying and understanding the function of genetic variants contributing to toxicities associated with chemotherapy.
Dr. Dolan began her independent career as a faculty member in 1989 in the Department of Medicine. Following her BS degree in chemistry from the University of Dayton, she obtained a PhD in medicinal chemistry from Purdue University and a post-doctoral fellowship at Pennsylvania State University. Both Dayton and Purdue have recognized her accomplishments through alumni awards including the University of Dayton Distinguished Alumni Award and Purdue University Distinguished Women Scholars Award, as well as the Purdue University School of Pharmacy Distinguished Alumni Award.
The Department of Medicine has been a fruitful environment for Dr. Dolan’s highly translational studies. She has dedicated her career to improving the quality of life of patients with cancer through identifying ways to increase effectiveness of chemotherapy while decreasing adverse side effects. She developed cell-based methods to identify genetic variants contributing to adverse events associated with chemotherapy. Her laboratory was the first to demonstrate that chemotherapeutic-induced cytotoxicity is a heritable trait. Since her approach integrates multiple large datasets including: genetic variation, gene expression, miRNA, modified cytosines, transcription factor levels and chemotherapeutic induced pharmacologic traits (cytotoxicity, apoptosis), her laboratory has been able to determine whether significant pharmacologic associated variants act through their effect on gene expression or protein levels. Her laboratory works closely with Nancy Cox, PhD, and her statistical genetics team. They made the seminal observation that pharmacologic SNPs, identified through genome wide association studies, are enriched in expression quantitative trait loci. Many researchers in the field of pharmacogenomics have utilized the cellular based model developed in her laboratory. Her work has received continual support from the NIH (R01, R21, UO1) including a large grant entitled, “Pharmacogenomics of Anticancer Agents Research (PAAR)” Group (co-PI’s: Drs. Dolan, Cox, and Mark Ratain, MD), which is part of the Pharmacogenomic Research Network (PGRN) through the NIGMS.
More recently, Dr. Dolan has focused her efforts on chemotherapy-induced peripheral neuropathy, the most common non-hematologic adverse event of multiple chemotherapeutic agents. This toxicity presents a quality of life issue, since the pain and disability may be permanent, and it is a common reason a chemotherapy regimen is dose reduced or permanently stopped early, which may have an impact on survival. At this time, clinicians are unable to predict which patients will experience toxicity, or the extent to which those patients will be affected. Her laboratory has recently extended her cell-based models to include human neurons derived from induced pluripotent stem cells. She is working closely with Gini Fleming, MD, to identify patients with severe chemotherapy-induced peripheral neuropathy, and creating induced pluripotent stem cell derived neurons to study the genetic and molecular underpinnings of this adverse drug effect. The use of patient derived cells as the entry point for discovering in vitro phenotypes associated with severe neuropathy will be an important step forward in the field.
Dr. Dolan is dedicated to education at all levels. As chair of the committee on clinical pharmacology and pharmacogenomics that includes a board-certified training program for clinical and post-doctoral fellows, she has initiated a cancer-focused PhD fellowship and an industry fellowship in clinical pharmacology. Under her direction, several clinical pharmacology fellows received national, peer-reviewed funding for their research projects while working in the laboratory and went on to careers in academic medicine. In addition to training graduate and undergraduate students, she partnered with high schools to bring under-represented minority students to the University for a weeklong boot camp followed by full-time work in a cancer research laboratory during the remainder of the summer. As associate director for education within the Comprehensive Cancer Center, she works closely with Kathy Goss, PhD, and Karen Kim, MD, to increase opportunities for high school students and undergraduates. Through their leadership, the Comprehensive Cancer Center received funding from the National Cancer Institute for a Continuing Umbrella of Research Experiences (CURE) program.
Over the past 20 years, Dr. Dolan has volunteered for the American Cancer Society, serving on their board of directors, helping to initiate their high school summer research program and giving lay presentations throughout Illinois to raise funds for research. She was recognized with a Presidential Award for Volunteer Contributions to Research for her efforts on their behalf.