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Last Updated: 4/7/2010
| 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 animal models as well as human renal carcinoma tissues and cell lines 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. For information on available clinical trials, please call (919) 966-9696.
Recent Accomplishments and Honors
National Cancer Institute R01 "Genetic Events in the development of Renal Cell Carcinoma"
AACR Landon Foundation 2010 INNOVATOR Award for Research in Personalized Cancer Medicine
American Cancer Society Research Scholar
ASCO 2010 Leadership Development Award
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
Refereed papers/articles, Original research
Brannon, A.R. *, Reddy, A.*, Seiler, M., Arreola, A., Moore, D.T., Pruthi, R., Wallen, E., Liu, H., Ljungberg, B., Zhao, H., Brooks, J.D., Ganesan, S., Bhanot, G., and Rathmell, W.K. Molecular Stratification of Clear Cell Renal Cell Carcinoma Reveals Distinct Subtypes and Survival Patterns. *Co-first authorship. Genes and Cancer. 2010. 1(2): 152-163. PMID: pending.
Chen, S., Sanford, C.A., Sun, J., Choi, V., Van Dyke, T., Samulski, R.J., and Rathmell, W.K. VHL and PTEN loss coordinate to promote liver vascular lesions. Angiogenesis. 2010. 13(1): 59-69. PMID: 20221685
Wright, T.M., Rathmell, W.K. Identification of Ror2 as a hypoxia inducible factor (HIF) target in von Hippel-Lindau (VHL)-associated renal cell carcinoma. Journal of Biological Chemistry. 2010. Epub ahead of print. PMID: 20185829
Cowey, C.L., Amin, C., Pruthi, R.S., Wallen, E.M., Nielsen, M.E., Grigson, G., Watkins, C., Nance, K.V., Crane, J., Jalkut, M., Kim, W.Y., Godley, P.A., Whang, Y.E., Fielding, J.R., and Rathmell, W.K. A Neoadjuvant Clinical Trial with Sorafenib for Patients with Stage II or Greater Renal Cell Carcinoma. Journal of Clinical Oncology. 2010. 28(9): 1502-7. PMID: 20159822
Pruthi, R.S., Nielsen, M., Heathcote, S., Wallen, E.M., Rathmell, W.K., Godley, P., Whang, Y., Fielding, J., Schultz, H., Grigson, G., Smith, A., Kim, W. A phase II trial of neoadjuvant erlotinib in patients with muscle-invasive bladder cancer undergoing radical cystectomy: clinical and pathological results. BJU Int. 2010 Jan 19. Epub ahead of print. PMID: 20089114
Kim WY, Whang YE, Pruthi RS, Baggstrom MQ, Rathmell W.K., Rosenman JG, Wallen EM, Goyal LK, Grigson G, Watkins C, Godley PA. Neoadjuvant docetaxel/ estramustine prior to radical prostatectomy or external beam radiotherapy in high risk localized prostate cancer: A phase II trial. Urol. Oncol. 2009. Epub ahead of print. PMID: 20022268
Cowey, C.L., Fielding, J., and Rathmell, W.K. The Loss of Radiographic Enhancement in Primary Renal Cell Carcinoma Tumors Following Multi-targeted Receptor Tyrosine Kinase Therapy is an Additional Indicator of Response. Urology. 2009, Nov 18, Epub ahead of print. PMID: 19931124
Kurpad, R, Kim, W.Y., Rathmell, W.K., Godley, P, Whang, Y., Fielding, J., Smith, L., Pettiford, A., Schultz, H., Nielsen, M., Wallen, E.M., Pruthi, R.S. A multidisciplinary approach to the management of urologic malignancies: Does it influence diagnostic and treatment decisions? Urologic Oncology. 2009, Epub ahead of print. PMID: 19576797
Wright, T. M., Brannon, A. R., Gordan, J. D., Mikels, A. J., Mitchell, C., Chen, S., Espinosa, I., van de Rijn, M., Pruthi, R., Wallen, E., Edwards, L., Nusse, R., and Rathmell, W. K. Ror2, a developmentally regulated kinase, promotes tumor growth potential in renal cell carcinoma. Oncogene, 28: 2513-2523, 2009. PMID: 19448672
Lee, C. M., Hickey, M. M., Sanford, C. A., McGuire, C. G., Cowey, C. L., Simon, M. C., and Rathmell, W. K. VHL Type 2B gene mutation moderates HIF dosage in vitro and in vivo. Oncogene, 28: 1694-1705, 2009. PMID: 19252526
Rathmell, W. K. and Monk, J. P. High-dose-intensity MVAC for Advanced Renal Medullary Carcinoma: Report of Three Cases and Literature Review. Urology, 72: 659-663, 2008. PMID: 18649931
Hacker, K. E., Lee, C. M., and Rathmell, W. K. VHL type 2B mutations retain VBC complex form and function. PLoS One, 3: e3801, 2008. PMID: 19030229
Gordan, J. D., Lal, P., Dondeti, V. R., Letrero, R., Parekh, K. N., Oquendo, C. E., Greenberg, R. A., Flaherty, K. T., Rathmell, W. K., Keith, B., Simon, M. C., and Nathanson, K. L. HIF-alpha effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma. Cancer Cell, 14: 435-446, 2008. PMID: 19061835
Amin, C., Wallen, E., Pruthi, R. S., Calvo, B. F., Godley, P. A., and Rathmell, W. K. Preoperative tyrosine kinase inhibition as an adjunct to debulking nephrectomy. Urology, 72: 864-868, 2008. PMID: 18684493
Hickey, M. M., Lam, J. C., Bezman, N. A., Rathmell, W. K., and Simon, M. C. von Hippel-Lindau mutation in mice recapitulates Chuvash polycythemia via hypoxia-inducible factor-2alpha signaling and splenic erythropoiesis. J Clin Invest, 117: 3879-3889, 2007. PMID: 17992257
Gollob, J. A., Rathmell, W. K., Richmond, T. M., Marino, C. B., Miller, E. K., Grigson, G., Watkins, C., Gu, L., Peterson, B. L., and Wright, J. J. Phase II trial of sorafenib plus interferon alfa-2b as first- or second-line therapy in patients with metastatic renal cell cancer. J Clin Oncol, 25: 3288-3295, 2007. PMID: 17664476
Rathmell, W. K., Malkowicz, S. B., Holroyde, C., Luginbuhl, W., and Vaughn, D. J. Phase II trial of 5-fluorouracil and leucovorin in combination with interferon-alpha and interleukin-2 for advanced renal cell cancer. Am J Clin Oncol, 27: 109-112, 2004. PMID: 15057147
Rathmell, W. K., Hickey, M. M., Bezman, N. A., Chmielecki, C. A., Carraway, N. C., and Simon, M. C. In vitro and in vivo models analyzing von Hippel-Lindau disease-specific mutations. Cancer Res, 64: 8595-8603, 2004. PMID: 15574766
Rathmell, W. K., Acs, G., Simon, M. C., and Vaughn, D. J. HIF transcription factor expression and induction of hypoxic response genes in a retroperitoneal angiosarcoma. Anticancer Res, 24: 167-169, 2004. PMID: 15015593
Mack, F. A., Rathmell, W. K., Arsham, A. M., Gnarra, J., Keith, B., and Simon, M. C. Loss of pVHL is sufficient to cause HIF dysregulation in primary cells but does not promote tumor growth. Cancer Cell, 3: 75-88, 2003. PMID: 12559177
Other peer reviewed articles (Reviews)
Rathmell, W.K, and Godley, P.A. Updates in Renal Cell Carcinoma. Current Opinion in Oncology. 2010. Epub ahead of print. PMID: 20154618
Rathmell, W.K., Pruthi, R., Wallen, E. Neoadjuvant treatment of renal cell carcinoma. 2010. Epub ahead of print. PMID: 20123351
Rathmell, W.K., Cowey, C.L., and Fielding, J. Reply: Is objective response rate
completely objective in kidney cancer? Improving radiographic assessment of targeted therapy in renal cell carcinoma. Urology, 2009, Nov 18. Epub ahead of print. PMID: 19931124
Cowey, C. L. and Rathmell, W. K. VHL gene mutations in renal cell carcinoma: role as a biomarker of disease outcome and drug efficacy. Curr Oncol Rep, 11: 94-101, 2009. PMID: 19216840
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.
Rini, B. I., Rathmell, W. K., and Godley, P. Renal cell carcinoma. Curr Opin Oncol, 20: 300-306, 2008.
Rathmell, W. K. and Chen, S. VHL inactivation in renal cell carcinoma: implications for diagnosis, prognosis and treatment. Expert Rev Anticancer Ther, 8: 63-73, 2008. PMID: 18095884
Rini, B. I. and Rathmell, W. K. Biological aspects and binding strategies of vascular endothelial growth factor in renal cell carcinoma. Clin Cancer Res, 13: 741s-746s, 2007. PMID: 17255303
Rathmell, W. K., Martz, C. A., and Rini, B. I. Renal cell carcinoma. Curr Opin Oncol, 19: 234-240, 2007. PMID: 17414642
Rini, B. I., Campbell, S. C., and Rathmell, W. K. Renal cell carcinoma. Curr Opin Oncol, 18: 289-296, 2006. PMID: 16552243
Rathmell, W. K., Wright, T. M., and Rini, B. I. Molecularly targeted therapy in renal cell carcinoma. Expert Rev Anticancer Ther, 5: 1031-1040, 2005. PMID: 16336094
Rathmell, W. K. and Simon, M. C. VHL: oxygen sensing and vasculogenesis. J Thromb Haemost, 3: 2627-2632, 2005. PMID: 15975138
Rathmell, W. K., Godley, P. A., and Rini, B. I. Renal cell carcinoma. Curr Opin Oncol, 17: 261-267, 2005. PMID: 15818172
Rathmell, W. K. and Godley, P. A. Renal cell carcinoma. Curr Opin Oncol, 16: 247-252, 2004. PMID: 15069321
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
