Associate Professor
Department of Surgery
Section of Transplantation
The University of Chicago
5812 S. Ellis Avenue
Chicago, IL 60637
SBRI J653
Phone (office): (773) 702-5882
Phone (lab): (773) 702-9765
Fax: (773) 702-1001
Email:
Appointments
Committee on Genetics
Education
University of Cincinnati, B.S. Chemistry/Biochemistry, 1986; University
of Kentucky, Ph.D., Biochemistry, 1992
• LAB PROFILES
Critical questions addressed work in the Rinker-Schaeffer Laboratory. Cancer metastasis is a complex, dynamic process that begins with dissemination of cells from the primary (1°) tumor and culminates in the formation of clinically detectable, overt metastases at one or more discontinuous secondary (2°) sites. The process of invasion has been well studied, but the last steps in metastasis, metastatic colonization, remain largely unknown [Fig. 1]. Identifying pathways that control metastatic colonization may be critical for successful clinical management of cancer in both the metastatic and adjuvant settings. While genetic mutations or epigenetic changes may be required for cells to separate and survive distant from the 1° tumor, the environment within 2° tissues plays a substantial role in determining whether disseminated cells survive and proliferate. Our work is focused on a critical unanswered question: Why do the majority of disseminated cells, which should be fully malignant, fail to proliferate immediately at 2° sites, and how do these cells initiate growth and cause lethal disease? Over the past decade, we have created unique model systems and developed biochemical tools to address this question mechanistically. This work is laying the foundation for the translational goal of identifying targets for inhibiting metastatic colonization and prolonging disease-free and overall survival.
Figure 1. Metastatic colonization is the final step in the development of metastases. After lodging at 2° sites, cells can either remain intravascular or extravasate. To form detectable metastases, disseminated cancer cells must activate signaling cascades, enabling them to survive; enter the cell cycle;and divide. Progressive growth requires the fraction of proliferating cells to exceed the fraction of cells that are non-dividing or apoptotic. [Adapted from [4]]
• Metastasis suppressors can be used to query the metastatic process.
• Discovery of JNKK1 as a metastasis suppressor protein.
• JNKK1 controls growth of cells at the metastatic site.
Vander Griend, D.J., Kocherginsky, M., Hickson, J.A., Stadler, W.M., Lin, A., Rinker- Schaeffer, C.W. Suppression of Metastatic Coloniztion by the Context-Dependent Activation of JNK Kinases JNKK1/MKK4 and MKK7. Cancer Res 65, 10984-10991, 2005. (PubMed)
Hickson, J.A. Huo, D., Vander Griend, D.J., Lin, A., Rinker-Schaeffer, C.W., Yamada, S.D. The p38 Kinase MKK4 and MKK6 Suppress Metastatic Colonization in Human Ovarian Cancer. Cancer Res. February 15, 2006. (PubMed)
Vander Griend, D.J., Rinker-Schaeffer, C.W. A New Look at an Old Problem: The Survival and Organ-Specific Growth of Metastases Science STKE 2004, pe4 (2004). (PubMed)
Kauffman E.C., Robinson V.L., Stadler W.M., Sokoloff M.H., Rinker-Schaeffer C.W. Metastasis suppression: the evolving role of metastasis suppressor genes for regulating cancer cell growth at the secondary site. J Urol. 169: 1122-33, 2003. (PubMed)
