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My research is centered on understanding molecular mechanisms that control cell proliferation and checkpoint responses, and how those processes are disrupted during tumorigenesis. A principal focus of the lab is the ARF tumor suppressor, which is encoded by a gene (INK4a/ARF) that is inactivated in 40-50% of all human cancers. ARF inhibits tumorigenesis through p53-dependent and p53-independent signaling pathways that are complex and only partially defined. That is because ARF functions through numerous binding partners (at least 30) to promote apoptosis or senescence, inhibit migration/invasion and metastasis, sustain cell stress checkpoints and maintain chromosomal stability. Our goal is to define the critical regulators of ARF signaling and determine their significance to tumor suppression using molecular approaches and in vivo models of cancer. In so doing, we will advance our fundamental understanding of ARF-mediated tumor suppression and also identify novel regulators of growth (both positive and negative) whose characterization will likely contribute to new paradigms of carcinogenesis. Such knowledge is essential to providing new markers for tumor detection and developing useful, targeted anticancer strategies.
Current projects:
| 1) |
Establishing the role of novel ARF-Mdm2-p53 regulators (NIAM and Parf) in tumor initiation and promotion using cultured cell systems and mouse models of cancer. |
| 2) |
Development and use of a novel mouse model of pancreatic cancer metastasis to test the role of various cancer genes in tumor metastasis. |
| 3) |
Role of ARF, NIAM and Parf in maintaining chromosomal stability using several different tumor model systems (B cell lymphoma, breast adenocarcinoma and pancreatic ductal adenocarcinoma). |
Representative Publications:
di Tommaso, A., Hagen, J., Tompkins, V., Muniz, V., Dudakovic, A., Kitzis, A., Ladeveze, V., and Quelle, D.E.: Residues in the alternative reading frame tumor suppressor that influence its stability and p53-independent activities. Experimental Cell Research 315(7):1326-35, 2009.
Hagen, J., Tompkins, V., Dudakovic, A., Weydert, J.A., and Quelle, D.E.: Generation and characterization of monoclonal antibodies to NIAM, a nuclear interactor of ARF and Mdm2. Hybridoma 27(3):159-166, 2008.
Tompkins, V., Hagen, J., Frazier, A.A. Lushnikova, T., Fitzgerald, M.P., di Tommaso, A., Ladeveze, V., Domann, F.E., Eischen, C.M., and Quelle, D.E.: A novel nuclear interactor of ARF and Mdm2 (NIAM) that maintains chromosomal stability. Journal of Biological Chemistry 282(2):1322-1333, 2007.
Tompkins, V., Hagen, J., Zediak, V.P. and Quelle, D.E.: Identification of novel ARF binding proteins by two-hybrid screening. Cell Cycle 5(6):641-646, 2006.
Korgaonkar,
C., Hagen, J., Tompkins, V., Frazier, A.A., Allamargot, C., Quelle,
F.W. and Quelle, D.E.: Nucleophosmin (B23) targets ARF to nucleoli and inhibits its function. Molecular & Cellular
Biology 25:1258-1271, 2005.
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here to see a list of additional publications
Center and Program affiliations:
Interdisciplinary
Graduate Program in Molecular & Cellular Biology
The
Medical Scientist Training Program
Biosciences
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