Hematologic & Oncogenic Disease

Kathryn Wikenheiser-Brokamp

Kathryn Wikenheiser-Brokamp, MD, PhD

Pathology & Lab Med

Assistant Professor

Research Summary

The laboratory focuses on understanding the mechanisms by which the retinoblastoma tumor suppressor protein, Rb, protects against cancer and regulates development. Rb plays a key role in regulating cell cycle progression and cell survival. The importance of Rb mediated regulation in tumor suppression is underscored by the observation that Rb is functionally inactivated in the majority of human tumors. Clinicopathologic data strongly support a prominent role for the Rb tumor suppressor in the etiology of lung cancer. In fact, the frequency of Rb inactivation in this tumor type is so high that it is assumed that disruption of the Rb pathway is essential for the genesis of lung cancer. In previous studies we have shown that Rb family proteins (Rb, p107 and p130) are essential regulators of cell proliferation, survival and differentiation in the developing lung epithelium in vivo. Rb, but not p107 and p130, has been shown to be a bone fide tumor suppressor in humans.

Therefore to elucidate Rb specific functions, an inducible lung epithelial specific Rb knockout mouse model was generated. This model provides the unique opportunity to directly address the role of Rb in epithelial biology in vivo by circumventing the embryonic lethality seen in conventional knockout strategies and by eliminating the concern that the phenotype may be secondary to abnormalities in other tissues. Current studies are focused on delineating the mechanisms through which Rb mediates its tumor suppressor function using this clinically relevant in vivo model. These studies will provide insight into the molecular basis of cancer development and progression; a fundamental step in the translation of research findings into novel detection and therapeutic modalities.

Recent Publications

Hill, D. A., Ivanovich, J. Priest, J. R., Gurnett, C. A., Dehner, L. P., Desruisseau, D., Jarzembowski, J. A., Wikenheiser-Brokamp, K.A., Suarez, B. K., Whelan, A. J., Williams, G, Bracamontes, D. Messenger, Y, and Goodfellow, P. J. DICER1 Mutations in Familial Pleuropulmonary Blastoma. Science, June 25 (Epub ahead of print), 2009.

Young, L.R., Franz, D.N., Nagarkatte, P., Fletcher, C.D.M.,Wikenheiser-Brokamp, K.A., Galsky, M.D., Lam, A., Gelfand, M.J. andMcCormack, F.X.: Utility of FDG-PET in Lymphangioleiomyomatosis andTuberous Sclerosis Complex. Chest, 2009 Apr 6 (Epub ahead of print)

Mason-Richie, N.A., Mistry, M.J., Gettler, C.A. Elayyadi, A., andWikenheiser-Brokamp, K.A.: Retinoblastoma function is essential forestablishing lung epithelial quiescence after injury. PMCID: PMC2518963,Cancer Res. 68 (11):4068-4076, 2008.

Duran, A., Linares, J.F., Galvez, A.S., Wikenheiser, K., Flores,J.M., Diaz-Meco, M.T. and Moscat, A.: The signaling adaptor p62 is animportant NF-κB mediator in tumorigenesis.  Cancer Cell 13(4):343-354,2008.

Wikenheiser-Brokamp, K.A.:  Retinoblastoma family proteins:insights gained through genetic manipulation of mice. Invited review.Cell. Mol. Life Sci. 63:767-780, 2006.

Wikenheiser-Brokamp, K.A.:  Retinoblastoma gene and lung cancer.Invited review. Curr. Mol. Med. 6(7):783-793, 2006.

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