The fundamental task of the cell cycle is to ensure that DNA is faithfully replicated once during S phase and that identical chromosomal copies are distributed equally to two daughter cells during mitosis. Genetic alterations affecting proteins that control cell cycle progression are frequently found in human cancers. Uncontrolled cell proliferation is the hallmark of cancer, and tumor cells have typically acquired damage to genes that directly regulated their cell cycles. A greatly majority of DNA damage is the result of environmental insults, such as exposure to irradiation and chemical mutagens. Our research primarily focus on identifying and characterizing proteins and their networks that regulate cell cycle progression and that contribute to the development of cancer when the networks are dysregulated. Our efforts incorporate the use of the state-of-the-art mass spectrometric analysis, molecular/biochemical and siRNA approaches to understand the functions of cell cycle regulatory proteins.

Using mammalian cells and mouse models, we are focusing on the following topics:

• Microtubule dynamics and cytokinesis
• Centrosome duplication and genomic stability
• protein post-translational modifications in response to DNA damage
• microRNAs in genomic stability and cell growth of mouse embryonic stem cells
• Genome stability-related phenotype screening in BXD, 8-way parental and collaborative cross heterozygous strains

• Giannone R, Liu Y, Wang Y. The Monitoring and affinity purification of proteins using dual-tags with tetracysteine motifs. Methods in Molecular Biology. [accepted].
• Wu J., Cho H., Rhee D., Johnson D, Dunlap J, Liu Y, Wang Y. Cdc14B depletion leads to centriole amplification and its overexpression prevents unscheduled centriole duplication J. Cell Biol. 2008 181: 475-483, 2008.
• Zou Y., Wu J., Giannone R., Boucher L., Hansen Du, Huang Y., Johnson D., Liu Y., and Wang Y. Nucleophosmin/B23 negatively regulates Gcn5-dependent histone acetylation and transactivation. J. Biol. Chem., 283, 9, 5728-5737, 2008.
• Giannone R, McDonald H, Hurst G, Huang Y, Wu J., Liu Y, Wang Y. Dual-tagging system for the affinity purification of mammalian protein complexes. BioTechniques 43, 296-302, 2007.
• Gomez M., Wu J., Schreiber V., Dunlap J., Dantzer, F., Wang Y, Liu Y. PARP1 is a TRF2-associated poly(ADP-ribose) polymerase and protects eroded telomeres. Molecular Biology of the Cell, 17, 1686-1696, 2006.
• Campbell MR, Wang Y, Andrew SE, Liu Y. Msh2 deficiency leads to chromosomal abnormalities, centrosome amplification, and telomere capping defect. Oncogene, 25, 17, 2531-2536, 2006.
• Cho H., Liu Y., Gomez M., Dunlap J., Tyers M., Wang Y. The dual specificity phosphatase Cdc14B bundles and stabilizes microtubules. Mol. Cell. Biol., 25, 4541-4551, 2005.
• Wang Y., Erdmann N., Giannone RJ, Wu J., Gomez M, Liu Y. Critically short telomeres are more permissive for end-to-end fusions and telomere sister chromatid exchange in telomerase deficient long-term culture murine embryonic stem cells than in mice. PNAS, 102, 10256-10260, 2005.
• Wang Y, Giannone R, and Liu Y. Telomere sister chromatid exchange in telomerase deficient murine cells. Cell Cycle, 4, 10, 1320-1322, 2005.
• Thyrell L., Sangfelt O., Zhivotovsky B., Pokrovskaja K., Wang Y., Einhorn S., Grander D. The HPV-16 E7 oncogene sensitizes malignant cells to IFN-alpha-induced apoptosis. J. Interferon & Cytokine Res. 25, 63-72, 2005.

• Wang Y., Penfold S., Tang X., Hattori N., Riley P., Harper WJ., Cross JC, Tyers M. Deletion of the Cul1 gene in mice causes arrest in early embryogenesis and accumulation of cyclin E. Curr. Biol., 9, 1191-1194, 1999.
• Silva S., Wang Y., Babonits M., Imreh S., Wiener F. and Klein G. Spontaneous development of plasmacytomas in a selected subline of BALB/cJ mice. Eur. J. Cancer, 33 (3), 479-485, 1997.
• Varmeh-Ziaie S., Okan I., Wang Y., Mugnusson K. and Wiman K. G. Wig-1, a new p53-induced gene encoding a zinc finger protein. Oncogene, 15, 2699-2704, 1997.
• Shick L., Carmen J., Choi J., Somasundaram K., Burrell M., Hill D.E., Wang Y., Wiman K.G., Kadesch T.R., Salhany, K. Monroe J., Donehower L.A., El-Deiry W.S. Decreased immunoglobulin deposition in tumors and increased immature B cells in p53 null mice. Cell Growth Differ 8,121-131, 1997.
• Wang Y., Okan I., Pokrovskaja K. and Wiman K. G. Abrogation of p53-induced G1 arrest by the HPV16 E7 protein does not inhibit p53-induced apoptosis. Oncogene, 12, 2731-2735, 1996.
• Wang Y., "The antagonistic role of activated oncogenes and apoptosis: studies of N-myc and p53 in lymphoid tumorigenesis". ISBN: 91-628-1878-3, 1996.
• Wang Y., Okan I., Szekely L., Klein G. and Wiman K. G. Bcl-2 inhibits wild type p53-triggered apoptosis but not G1 cell cycle arrest and transactivation of WAF1 and Bax. Cell Growth & Diff., 6, 1071-1075, 1995.
• Okan I., Wang Y., Klein G. and. Wiman K.G. The EBV-encoded LMP1 protein inhibits p53-triggered apoptosis but not growth arrest. Oncogene, 11, 1027-1031, 1995.
• Szekely L., Wang Y., Klein G. and Wiman K.G. Rb reconstituted human retinoblastoma cells form Rb positive intraocular and intracerebral but not subcutaneous tumors in SCID mice. Int. J. Cancer, 61, 683-691, 1995.
• Axelson H., Henriksson M., Wang Y. and Klein G. The amino-terminal phosphorylation sites of c-myc are frequently mutated in Burkitt's lymphoma lines but not in mouse plasmacytomas and rat immunocytomas. Eur. J. Cancer, 31A, 2099-2104, 1995.
• Wang Q., Hu L-F., Chen F., Wang Y., Magnusson K. P., Kashuba E., Klein G. and Wiman K.G. Infrequent MDM2 gene amplification and absence of gross WAF1 gene alterations in nasopharyngeal carcinoma. Eur. J. Cancer, 31B, 328-332, 1995.
• Axelson H., Wang Y., Silva S., Mattei M.G and Klein G. Juxtaposition of N-myc and Igk through a reciprocal t(6;12) translocation in a mouse plasmacytoma. Genes Chr. Cancer, 11, 85-90, 1994.
• Sugiyama H., Wang Y., Jackson P., Sawyer C.L., and Klein G. Molecular requirements for rapid plasmacytoma and pre-B lymphoma induction by Abelson murine leukemia virus in myc-transgenic mice. Int. J. Cancer, 58, 135-141, 1994.
• Imreh S., Wang Y., Panda C. K., Axelson H., Babonits M., Panda C., Silva S., Wiener F. and Klein G. Hypersomy of chromosome 15 with retrovirally rearranged c-myc, loss of germline c-myc and Igk/c-myc juxtaposition in a macrophage-monocytic tumor line. Eur. J. Cancer, 30A, 994-1002, 1994.
• Liu Y, Heyman M, Wang Y., Szekely L., Vanky F and Einhorn S. Molecular analysis of the retinoblastoma gene in primary ovarian cancer cells. Int. J. Cancer, 58, 663-667, 1994.
• Sugiyama H., Silva S., Wang Y. and Klein G. Strain-related cellular mechanisms as a determinant for susceptibility and resistance to PC induction. Curr. Top. Microbiol. Immunol. 194, 93-97, 1994.
• El-Deiry W.S., Harper J.W., O´Connor P.M.,Velculescu V.E., Canman C.E., Jackman J.,Pietenpol J.A.,Burrelll M., Wang Y., Wiman K.G., Mercer W.E., Kastan M.B., Kohn K.W., Elledge S.J., Kinzler K.W., Vogelstein B. Waf1/Cip1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res. 54, 1169-1174, 1994.
• Wang Y., Ramqvist T., Szekely L., Axelson H., Klein G. and Wiman K. Reconstitution of wild-type p53 expression triggers apoptosis in a p53 negative v-myc retrovirus-induced T cell lymphoma line. Cell Growth & Diff., 4, 467-473, 1993.
• Wang Y., Szekely L., Okan I., Klein G. and Wiman K. G. Wild-type p53-triggered apoptosis is inhibited by bcl-2 in a v-myc-induced T-cell lymphoma line. Oncogene, 8, 3427-3431, 1993.
• Ramqvist T., Magnusson K.P., Wang Y., Szekely L., Klein G., and Wiman K.G. Wild-type p53 induces apoptosis in a Burkitt lymphoma line that carries mutant p53. Oncogene, 8, 1495-1500, 1993.
• Wang Y., Sugiyama H., Axelson H., Panda C. K., Babonits M., Ma A., Steinberg J. M., Alt F.W., Klein G. and Wiener F. Functional homology between N-myc and c-myc in murine plasmacytomagenesis: plasmacytoma development in N-myc transgenic mice. Oncogene, 7, 1241-1247, 1992.
• Silva S., Wang Y., Babonits M., Axelson H., Wiener F. and Klein G. An exceptional mouse plasmacytoma with a new kappa/N-myc T(6; 12) (C1; B) translocation expresses N-myc but not c-myc. Curr. Top. Microbiol. Immunol. 182, 251-259, 1992.
• Nojima T., Wang Y., Abe S., Natsuno T., Yamawaki S. and Nagashima K. Morphological and cytogenetic studies of a human synovial sarcoma xenotransplanted in nude mice. Acta Pathologica Japanica 40, 486-493, 1990.
• Sugiyama H., Silva S., Wang Y., Weber G., Wiener F. and Klein G. Abelson murine leukemia virus transforms preneoplastic Em-myc transgene-carrying cells of the B-lymphocyte lineage into plasmablastic tumors. Int. J. Cancer, 46, 845- 852, 1990.