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Last Updated: 5/6/2009
| W. Kimryn Rathmell, MD, PhD
Assistant Professor |  |
Clinical Interests
Renal Cell Carcinoma, clinical trials for advanced disease.
Von Hippel-Lindau Disease
Research Interests
The focus of my research group is the understanding of the tumorigenesis of renal cell carcinoma. Our group takes a broad approach to this cancer, utilizing mouse models, molecular strategies, and translational studies. We have developed several strains of genetically engineered murine models bearing clinically important point mutations in the von Hippel-Lindau (VHL) tumor suppressor gene, which is mutated in over 80% of clear cell renal cell carcinomas (conventional kidney cancer). These mice provide a tool for the in vivo study of cellular VHL activity as well as the ability to generate a number of animal model systems for tumor growth and development. Using these models we are able to investigate the effects of VHL on processes integral to tumorigenesis including angiogenesis, vasculogenesis, hypoxic response signaling, extracellular matrix remodeling, and cell cycle signaling. These genetically targeted animals additionally provide the platform for an examination of the necessary genetic changes in addition to VHL loss or mutation required to generate an invasive renal cell carcinoma. Finally, in vitro and in vivo models of VHL mutation provide a useful way to test unique molecules with the potential for use as diagnostic or therapeutic tools in human renal cell carcinoma.
Clinical trials which incorporate translational studies of the effect of novel cancer treatments in the setting of renal cell carcinoma are ongoing all stages of this disease. For information on available clinical trials, please call (919) 966-9696.
Recent Accomplishments and Honors
National Cancer Institute Career Development Award "Functional and Tissue Specific Effects of VHLMutations"
Valvano Scholar Award, The V Foundation for Cancer Research
American Cancer Society Research Scholar
Doris Duke Foundation Scholar
Forbeck Foundation Scholar Award
Training
PhD Biophysics, Stanford University, 1996
MD, Stanford University, 1998
Internship, University of Chicago
Residency, University of Pennsylvania
Oncology Fellowship, University of Pennsylvania
Publications
Wright, T.M., Gordan, J.D., Chen, S., Brannon, A.R., Mikels, A., Mitchell, C., Edwards, L., and Rathmell, W.K. Ror2 is a HIF-2 dependent kinase that promotes invasive growth potential in renal cell carcinoma. Oncogene. In press.
Rathmell, W.K., Pruthi, R., Wallen, E. Preoperative use of TKI prior to nephrectomy. Urologic Oncology. In press.
Lee, C.A., Hickey, M.M., Sanford, C.A., McGuire, C.G., Simon, M.C., and Rathmell, W.K. VHL Type 2B mouse model regulates HIF yet confers embryonic lethality and sensitivity to mutagenesis. Oncogene. 28(14):1694-705, 2009
Cowey, C.L. and Rathmell, W.K. VHL Gene Mutations in Renal Cell Carcinoma: Role as a Biomarker of Disease Outcome and Drug Efficacy. Current Oncology Reports. 11(2):94-101, 2009.
Gordan, JD, Lal, P, Dondeti, VR, Letrero, R, Parekh, KN, Oquendo, CE, Greenberg, RA, Flaherty, KT, Rathmell, W.K., Keith, B, Simon, MC, Nathanson, KL. HIF-alpha effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma. Cancer Cell. 14:435-46. 2008.
Cowey, C.L. and Rathmell, W.K. Using Molecular Biology to Develop Drugs for Renal Cell Carcinoma. Expert Opinion on Drug Discovery 3(3): 311-327, 2008.
Hacker, K.E., Lee, C.M., and Rathmell, W.K. VHL 2B mutation retains E3 ubiquitin ligase form and function. PLoS One. 3(11):e3801. 2008.
Rini, B.I., Rathmell, W.K. and Godley, P.A. Renal Cell Carcinoma. Current Opinion in Oncology. 20(3): 300-6, 2008.
Rathmell, W.K. and Monk, J.P. High dose intensity MVAC in renal medullary carcinoma: a report of three cases and review of the literature. Urology. 72(3):659-63. 2008.
Amin, C.J., Wallen, E., Pruthi, R.S., Calvo, B.F., Godley, P.A., Rathmell, W.K. Preoperative treatment of renal cell carcinoma with tyrosine kinase inhibition. Urology. 72(4):864-8. 2008.
Rathmell, W.K. and Chen, S. VHL inactivation in renal cell carcinoma: implications for diagnosis, prognosis, and treatment, Expert Rev Anticancer Ther. 8(1):63-73, 2008.
Gollob, J., Rathmell, W.K. et al. Phase II trial of sorafenib plus interferon alpha-2b as first- or second-line therapy in patients with metastatic renal cell cancer. J Clin Oncol. 25:3288-3295, 2007
Hickey, M.M., Lam J.C., Bezman N.C., Rathmell, W.K., and Simon, M.C., von Hippel-Lindau mutation in mice recapitulates Chuvash polycythemia via hypoxia-inducible factor-2α signaling and splenic erythropoiesis. J Clin Invest. 117(12):3879-89, 2007
Rini, B.I., Rathmell, W.K Biological aspects and binding strategies of vascular endothelial growth factor in renal cell carcinoma. Clin Cancer Res. 13(2 Pt 2):741s-746s, 2007.
E-mail: rathmell@med.unc.edu
Telephone: (919) 966-8644
FAX: (919) 843-3160
Address: Lineberger Cancer Center, 21-237 Chapel Hill, NC 27599
URL: www.unc.edu/~rathmell
