Neli Ulrich, PhD, MS
Associate Member, Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center
Cancer Prevention Research Center
1100 Fairview Ave N., M4-B402
PO Box 19024
Seattle, WA 98109-1024
My research centers on studies in molecular epidemiology. This discipline integrates knowledge from the laboratory sciences (for example with respect to gene function) with epidemiologic methods for investigating the causes of diseases. Cancer is a multifactorial disease, caused by both genetic and environmental factors. Combining molecular information with human studies on disease occurrence and extensive exposure information (e.g. on dietary factors) provides a powerful approach towards cancer prevention. Areas that interest me include the metabolism of the nutrient folate, the cyclooxygenase (COX) pathway, and DNA repair mechanisms. In collaboration with Dr. Potter and others, I conducted a study investigating the relation between a polymorphism in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) and colorectal polyps. We observed associations with various nutrients (folate, vitamin B12, vitamin B6) that differed depending on the MTHFR genotype: the combination of a low-enzyme-activity genotype and low nutrient intakes resulted in increased risk of colorectal polyps. These results can be explained by the relationship between these nutrients and MTHFR, and raise some interesting hypotheses regarding the molecular mechanisms involved, in particular nucleotide synthesis and DNA repair capacity. Currently, I am continuing this research by pursuing the relationship between colorectal polyps and polymorphisms in other enzymes in folate metabolism and DNA repair enzymes, as well as biomarkers of DNA damage. Folate is also of major importance in pharmacology, in particular with respect to antifolate chemotherapeutic drugs. Genetic variability in folate-metabolizing enzymes may affect treatment outcomes and side effects. Thus, an additional area of interest to me is pharmacogenetics, with emphasis on antifolate agents. As part of a collaborative study with the Clinical Division I investigated whether the toxicity of methotrexate (MTX) differed depending on patients' MTHFR genotype. This study showed that marrow transplantation patients with decreased MTHFR enzyme activity are at risk of higher MTX toxicity, as evidenced by >30% higher oral mucositis scores and delayed platelet recovery. If these results are confirmed, genotyping patients for this common polymorphism may allow tailoring of MTX dose or use of alternative regimens based on a patient's genotype. I am extending this avenue of research by investigating polymorphisms in other key enzymes in folate metabolism and their effect on MTX toxicity and hope to expand this research to other antifolate drugs. A third area of my research is immunoepidemiology. Some cancer-preventing behaviors (such as physical activity or nutrition) may reduce cancer incidence via enhancing immune function. Recent improvements in immunologic methods have begun to open up this area for large-scale epidemiologic investigations. A current study in collaboration with Dr. Anne McTiernan investigates the effects of a one-year aerobic exercise or stretching exerciseprogram on various markers of immune function among postmenopausal women. In addition to studies of exercise, we plan a number of analyses relating immune function to hormone levels, lifetime physical activity, diet, and anthropometric characteristics. In summary, my goals are to utilize the new tools of molecular epidemiology -- information on genetic polymorphisms and relevant biomarkers -- to further cancer prevention and possibly cancer therapy.
Dr. Ulrich teaches EPI 540 "Introduction to Cancer Biology" during Spring Quarter (even years).
PhD, Epidemiology, University of Washington 1998
MS, Nutritional Science, Oregon State University 1992
Ulrich, C. M., Robien, K., and McLeod, H. L. Cancer pharmacogenetics: polymorphisms, pathways and beyond. Nat Rev Cancer, 3: 912-20, 2003.
Ulrich, C. M., Whitton, J., Yu, J. H., Sibert, J., Sparks, R., Potter, J. D., and Bigler, J. PTGS2 (COX-2) -765G > C promoter variant reduces risk of colorectal adenoma among nonusers of nonsteroidal anti-inflammatory drugs. Cancer Epidemiol Biomarkers Prev, 14: 616-9, 2005
Ulrich, C. M., Bigler, J., and Potter, J. D. Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils, and pharmacogenetics. Nature Reviews Cancer, 6: 130-40, 2006.
Chubak, J., McTiernan, A., Sorensen, B., Wener, M. H., Yasui, Y., Velasquez, M., Wood, B., Rajan, K. B., Wetmore, C. M., Potter, J. D., and Ulrich, C. M. Moderate-intensity exercise reduces the incidence of colds among postmenopausal women. Am J Med, 119: 937-42, 2006
Reed, M. C., Nijhout, H. F., Neuhouser, M. L., Gregory, J. F., 3rd, Shane, B., James, S. J., Boynton, A., and Ulrich, C. M. A mathematical model gives insights into nutritional and genetic aspects of folate-mediated one-carbon metabolism. J Nutr, 136: 2653-61, 2006
Ulrich, C. M., and Potter, J. D. Folate and cancer--timing is everything. Jama, 297: 2408-9, 2007