Richard Weinshilboum, M.D. studies pharmacogenomics — the role of inheritance and individual variation in DNA sequence or structure in drug response. The goal is to develop safer and more effective drug therapy to treat diseases that range from cancer to depression.
Dr. Weinshilboum's research program utilizes genomic techniques that include genome-wide association studies (GWAS) and "next-generation" whole genome DNA sequencing using samples from large numbers of patients treated with a specific anticancer or antidepressant drug. Sophisticated cell-based functional genomic techniques are used to determine mechanisms responsible for variation in drug response phenotypes. This approach has already succeeded in the discovery and functional/mechanistic pursuit of novel, unanticipated genes that influence response to a series of drugs used to treat childhood leukemia and breast cancer.
Dr. Weinshilboum's research has been continuously funded for decades by the National Institutes of Health and other Foundation funding mechanisms.
- Why some children with childhood leukemia develop life-threatening adverse drugs reactions. Acute lymphoblastic leukemia (ALL) is the number one cancer of children, but one that can now be cured in approximately 90% of these children with appropriate drug therapy, but tragically a few children also can develop life-threatening adverse drug reactions. Dr. Weinshilboum's research program identified genetic variation in the expression of TPMT, an enzyme that the body uses to metabolize one of the major classes of anti-ALL drugs. Subsequently, this research program cloned the TPMT gene, and characterized the genetic variation which is now an FDA-recommended test to avoid life-threatening drug toxicity in these children.
- Why women with breast cancer develop drug-related toxicity or fail to respond to therapy. Using GWAS as applied to large numbers (thousands) of DNA samples from patients with breast cancer, Dr. Weinshilboum's research program has identified a series of novel genes that are associated with variations in the toxicity or efficacy of drugs used to treat breast cancer and, equally important, it has pursued those observations with functional studies that have served to illuminate novel biology and novel drug mechanisms that have led to previously unappreciated pharmacogenomic mechanisms.
Significance to patient care
Dr. Weinshilboum's research into mechanisms responsible for large individual variation in drug toxicity or efficacy will help to enhance the treatment of diseases as diverse as breast cancer, childhood leukemia or depression.
- Harry Gold Award for Clinical Pharmacology, American Society for Pharmacology and Experimental Therapeutics, 2003
- Oscar B. Hunter Award for Career Scientific Accomplishments, American Society for Clinical Pharmacology and Therapeutics, 1998
- Council Member, National Institute for General Medical Science, NIH, 2000-2003
- Council Member, National Human Genome Research Institute, NIH, 2007-2010
- Director for Research, Mayo Foundation, 1984-88
- Director for Education, Mayo Foundation, 1992-99
See my publications
- Professor of Medicine
- Professor of Pharmacology
- Senior Resident - Internal Medicine Massachusetts General Hospital
- Fellow PRAT, NIMH, National Institutes of Health
- Assistant Resident - Internal Medicine Massachusetts General Hospital
- Internship - Internal Medicine Massachusetts General Hospital
- MD University of Kansas Medical School
- Fellow - Exchange Fellowship Tuebingen University
- BA - Chemistry and Zoology University of Kansas