Caroline Alexander
Assistant Professor of Cancer Biology
- Address:
- 819 McArdle Lab
- Telephone:
- 265-5182
- Email:
- alexander@wisc.edu
- Research Fields:
- Cancer Genetics
- Developmental Genetics
- Mouse Genetics
Ph.D., University of Kent at Canterbury
Postdoctoral Research: University of California, San Francisco and Harvard Children’s Hospital, Boston
Research Interests
Mammary Epithelial Cell Biology and Neoplasia
Research Description
The mouse mammary gland is a genetically tractable model of development and pathogenesis, and the Alexander lab studies several aspects of mammary epithelial cell growth regulation and neoplasia. Currently, we are following up on our observation that tumors induced by ectopic Wnt signaling are preceded by dysregulation of the stem/progenitor compartment. These mice are therefore excellent models for studying a large number of human tumors that develop in response to activating mutations in the Wnt signaling pathway.
Specifically, we propose to determine why Wnt-induced stem cell compartments are so easily transformed. This depends on the evaluation of mammary development in vivo, and upon the development of faithful tissue culture models. We also aim to use in vivo reconstitution and transgenesis to evaluate other, non-oncogenic activities of the Wnt ligands during mammary development. We have found a strain of mouse (bearing a mutation in the cell surface heparan sulfate proteoglycan, syndecan-1) that is not susceptible to stem cell-based tumor development. We aim to find out how and why this strain is resistant. We propose that this result will enable us to understand more about the risks associated with division of the somatic stem cell compartment.
Representative Publications
- Paguirigan, C.M. Alexander and D. Beebe. 2005. A mathematical model for predicting murine mammary epithelial cell population demographics during development and neoplasia. J. Theor. Biol. (accepted March 2005)
- B. Liu, S. McDermott, S.S. Khwaja, and C.M. Alexander, 2004. The transforming activity of Wnt effectors correlates with their ability to induce the accumulation of mammary progenitor cells. Proc. Natl. Acad. Sci. 101:4159-4163.
- T. Maeda, C.M. Alexander and A. Friedl. 2004. Induction of syndecan-1 expression in stromal fibroblasts promotes proliferation of human breast cancer cells. Cancer Res. 64:612-621.
- B. Liu, Y-C. Kim, V. Leatherberry, P. Cowin and C.M. Alexander. 2003. Mammary gland development requires syndecan-1 to create a β-catenin/tcf-responsive mammary epithelial sub-population. Oncogene. 22:9243-9253.