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Yaswen Lab

Research Interest

The Yaswen laboratory studies how intrinsic and extrinsic factors interact to cause malignancy in human epithelial cells that line the cavities and surfaces of structures throughout the body, and also form many glands.  Most human cancers are epithelial in origin and show steep age-dependent increases in incidence.  These sharp increases are thought to be due to accumulated changes in gene expression and function that over time favor the development of growth autonomy and invasiveness in susceptible cells.

One of nature’s notable tumor suppressive mechanisms is cellular senescence - a viable growth arrest characterized by the inability of affected cells to proliferate in the presence of appropriate mitogenic factors. Abundant published evidence now supports the concept that senescence is a primary impediment to malignancy, and that it is ordinarily very stringent. Despite the resiliency of the senescence response, however, it is prone to failure to varying degrees, depending upon genetic/epigenetic context. Moreover, additional evidence indicates that processes, such as oncogene activation, telomere dysfunction, and DNA damage, that ordinarily result in senescence, can contribute to malignancy- and drug resistance-favoring changes in cells in which senescence fails. One goal in the Yaswen lab is therefore the elucidation of mechanisms that enforce senescence in the expectation that such knowledge should lead to measures that prevent or reverse its failure in susceptible pre-malignant and malignant cell populations without limiting the regenerative abilities of normal stem/progenitor cells.

Another goal is to use cultured human breast cells to develop and use tissue specific risk models of carcinogenesis. While it is not currently possible to simulate cancer progression in its entirety using cultured human cells, assays employing such cells under conditions in which aberrant differentiation and self-renewal can be detected may be important surrogate endpoints that can be used directly in estimates of cancer risk.

Selected Publications

Nguyen-Ngoca, K-V., Cheung, K.J., Brenot, A., Shamira, E.R., Gray, R.S., Hines, W.C., Yaswen, P., Werb, Z., and Ewald, A.J. The ECM microenvironment regulates collective migration and local dissemination in normal and malignant mammary epithelium. Proc. Nat. Acad. Sci. (USA) 109:E2595-604, 2012.

Littlepage, L.E., Adler, A.S., Kouros-Mehr, H., Huang, G., Chou, J., Krig, S.R., Griffith, O.L., Korkola, J.E., Qu, K., Lawson, D.A., Xue, Q., Sternlicht, M.D., Dijkgraaf, G.J., Yaswen, P., Rugo, H.S., Sweeney, C.A., Collins, C.C., Gray, J.W., Chang, H.Y., and Werb, Z. The transcription factor ZNF217 is a prognostic biomarker and therapeutic target during breast cancer progression. Cancer Discov. 2:638-51, 2012.

Horiuchi, D., Kusdra, L., Huskey, N.E., Chandriani, S., Lenburg, M.E., Gonzalez-Angulo, A.M., Creasman, K.J., Bazarov, A.V., Smyth, J.W., Davis, S.E., Yaswen, P., Mills, G.B., Esserman, L.J., Goga, A. MYC pathway activation in triple-negative breast cancer is synthetic lethal with CDK inhibition. J Exp Med. 209:679-96, 2012.

Bazarov, A.V, Lee, W.J., Bazarov, I., Bosire, M., Hines, W.C., Stankovich, B., Chicas, A., Lowe, S.W., and Yaswen, P. The specific role of pRb in p16INK4A mediated arrest of normal and malignant human breast cells. Cell Cycle 11:1008-1013, 2012.

Krig, S.R., Miller, J.K., Frietze, S., Beckett, L.A., Neve, R.M., Farnham. P.J., Yaswen, P.I., and Sweeney, C.A. ZNF217, a candidate breast cancer oncogene amplified at 20q13, regulates expression of the ErbB3 receptor tyrosine kinase in breast cancer cells. Oncogene 29:5500-10, 2010.

Bazarov, A.V., Hines, W.C., Lee, L., Bassett, E., Beliveau, A., Campeau, E., Mukhopadhyay, R., Lee, W.J., Melodyev, S., Zaslavsky, Y., Rodier, F., Benhattar, J., Ren, B., Campisi, J., and Yaswen, P.  P16INK4A mediated suppression of telomerase in normal and malignant human breast cells. Aging Cell 9:736-46, 2010.

Mukhopadhyay, R., Costes, S., Bazarov, A., Hines, W.C., Barcellos-Hoff, M.H., and Yaswen, P. Promotion of variant human mammary epithelial cell outgrowth by ionizing radiation: an agent-based model supported by in vitro studies. Breast Cancer Res. 12:R11, 2010.

Bazarov, A., Hines, W.C., Mukhopadhyay, R., Beliveau, A., Melodyev, S., Zaslavsky, Y., and Yaswen, P. Telomerase activation by c-Myc in human mammary epithelial cells requires additional genomic changes. Cell Cycle 8: 3373-3378, 2009.

 

Yaswen

Paul Yaswen

Staff Scientist/
Life Sciences Division

Department:
Cancer & DNA Damage Responses

Berkeley Lab
One Cyclotron Rd.
Mailstop: 977
Berkeley, CA  94720-8174
Tel.: (510) 486-4192
Fax:  (510) 486-5586
E-mail: P_Yaswen@lbl.gov
Biosketch: PDF