Member, IME Assistant Professor Department of Pathology and Laboratory Medicine 1170 Vagelos Research Labs 3340 SmithWalk Philadelphia, PA 19104-6160 (215) 573-7389, phone (215) 573-7227, fax vmweaver@mail.med.upenn.edu Education Post-doctoral Fellow (1992-1994) Molecular Cell Biology and Apoptosis Research Group, Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada Post-doctoral Fellow (1994-1998) Cancer and Cell Biology Group, Life Sciences Division, Lawrence Berkeley National Laboratory UC Berkeley, Berkeley, CA Professional Experience Research Scientist, Cancer and Cell Biology Group, Life Sciences Division, Cell and Molecular Biology Group, Lawrence Berkeley National Laboratory, CA, 1998 to 1999 Research Interests Dr. Weaver joins Penn and the IME as in September 1999 from UC Berkeley, where she is currently in the Life Sciences Division at Lawrence Berkeley National Laboratory. She is a Summa cum Laude graduate in Biochemistry of the University of Ottawa, where she received her Ph.D. Author of more than 30 full-length publications, Valerie is an exceptional and innovative investigator. Her work involves the study of mechanisms and relevance of epithelial cell tumor "dormancy," the role of cell adhesion molecules, cell geometry tension, and nuclear architecture in apoptosis regulation, identification of architectural transcription factors mediating tumor "dormancy" and resistance to apoptosis induction, and the regulation of integrin expression. Dr. Weaver is using a novel mammary epithelial tumor progression series in conjunction with a 3-dimensional basement membrane assay. The model system recapitulates many of the architectural and behavioral characteristics observed during breast cancer in vivo. At present, tissue polarity has been identified as a critical feature of organized tissues and has been shown to function in facilitating a reciprocal cross modulation between integrins (extracellular matrix receptors) and growth factor receptors in the regulation of growth and death decisions in the cell. The laboratory is now focusing on delineating the underlying mechanism for this tissue structure-mediated modulation of growth and death regulation. Specifically, the focus is upon the role of b4 integrins, and several tissue architecture-modulated tyrosine phosphatases that have been identified, cloned, and characterized. Selected Publications Weaver, V.M. and Bissell, M.J. Functional culture models for studying mechanisms governing mammary epithelial cell apoptosis in normal and malignant breast. J. Mammary Gland Biology Neoplasia. 4:193-201, 1999. Weaver, V.M.*, Wang, F.*, Petersen, O.W., Larabell., C., Dedhar, S., Briand, P., Lupu, R. and Bissell, M.J. b1-integrins and epidermal growth factor receptors are cross-modulated in three dimension and not in monolayer culture: a new perspective in normal and malignant epithelial biology. Proc. Natl. Acad. Sci. USA. 95:14821-14876, 1998. *both authors contributed equally to the work Lelievre, S., Weaver, V.M., Nickerson, J., Larabell., C.A., Bhaumik, A., Petersen, O., and Bissell, M.J. Tissue phenotype is dependent on reciprocal interactions between the extracellular matrix and the structural organization of the nucleus. Proc. Natl. Acad. Sci. USA. 95:14711-14716, 1998. Weaver, V.M., Petersen, O.W., Wang, F., Larabell, C.A., Briand, P., Damsky, C. and Bissell, M.J. Reversion of the malignant phenotype of human breast cells in 3-dimensional culture and in vivo by integrin blocking antibodies. J. Cell Biol. 137:1-15, 1997. Weaver, V.M., Carson, C.E., Walker, P.R., Chaly, N., Lach, B., Raymond, Y., Brown, D.L. and Sikorska, M. Correlations between DNA cleavage and degradation of nuclear matrix in apoptotic thymocytes. J. Cell Sci. 109:45-56, 1996. Weaver, V.M., Fischer, A.H., Petersen, O.W., and Bissell, M.J. The importance of the microenvironment in breast cancer progression: recapiulation of mammary tumorigenesis using a unique human mammary epithelial cell model and a 3-dimensional culture assay. Biochem. Cell Biol. 74:833-851, 1996. Back to IME Home Page
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