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Caroline Alexander, Ph.D.

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AlexanderPhotoAssociate Professor of Oncology

B.Sc., 1982, Biochemistry, University of Aberdeen, Scotland
Ph.D., 1985, Cell Biology and Biochemistry, University of Kent, England
Postdoctoral research: Imperial Cancer Research Fund, London and UC-San Francisco

Office: 819A McArdle Laboratory
Telephone: Office - (608) 265-5182; Lab - (608) 262-1258
Email: alexander@oncology.wisc.edu

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Research Interests: Mammary stem cells; Mouse mammary tumor models; Wnt signaling; Syndecan-1

Research Description: We are studying aspects of mammary gland biology and neoplasia using transgenic mouse models. Particularly, we have found that Wnt signaling dysregulates mammary stem cells, and that this precedes the formation of differentiated, bilineal tumors.  Wnt signaling is highly oncogenic to mammalian epithelia, and indeed comprises one of the main sources of human tumor initiation identified to date.  Our hypothesis is that the transforming potential of Wnt signaling is unique to stem/progenitor cells.  Our work aims at elucidating how and when adult somatic stem cells can be recruited as tumor precursor cells.  Current projects include:

  1. The discovery of the molecular and cellular mechanism that underlies the tumor resistance phenotype illustrated by mice with a mutation in the heparan sulfate proteoglycan, syndecan-1 (Sdc1) (McDermott et al 2006). 
  2. Modeling of stem cell-based breast cancer
  3. The activation of stromal cells and their recruitment to tumor development during Wnt-induced tumorigenesis
  4. The analysis of adult stem cell responses during tumor initiation
  5. Determination of how Wnt signaling supports normal mammary stem cell function
  6. An investigation of cell-cell interactions in mammary gland, using microchannel cultures to identify endogenous growth promoting and inhibiting substances secreted by minor sub-populations

CMA is the recipient of an Era of Hope Scholar Award 2006 – 2011 (Dept. of Defense)

Selected recent publications

Goel, S., Chin, E. N., Fakhraldeen, S. A., Berry, S. M., Beebe, D. J., and Alexander, C. M.  Both Lrp5 and Lrp6 Receptors Are Required to Respond to Physiological Wnt Ligands in Mammary Epithelial Cells (and Fibroblasts).  J. Biol. Chem., in press, 2012 [Epub ahead of print Mar 20 2012].

Gunsalus, K. T. W., Wagoner, M. P., Meyer, K., Potter, W. B., Schoenike, B., Kim, S., Alexander, C. M., Friedl, A., and Roopra, A.  Induction of the RNA Regulator LIN28A Is Required for the Growth and Pathogenesis of RESTless Breast Tumors.  Cancer Res., in press, 2012 [Epub ahead of print Apr 24 2012].

Kim, S., Roopra, A., and Alexander, C. M.  A Phenotypic Mouse Model of Basaloid Breast Tumors.  PLoS ONE, 7(2):e30979, 2012.

Kim, S., Goel, S., and Alexander C. M. Differentiation Generates Paracrine Cell Pairs That Maintain Basaloid Mouse Mammary Tumors: Proof of Concept. PLoS One, 6(4):e19310, 2011.

Mastroianni, M., Kim, S., Kim, Y. C., Esch, A., Wagner, C., and Alexander, C. M.  Wnt Signaling Can Substitute for Estrogen to Induce Division of ERα-Positive Cells in a Mouse Mammary Tumor Model.  Cancer Lett., 289: 23-31, 2010.

Alexander, C. M., Puchalski, J., Klos, K. S., Badders, N., Ailles, L., Kim, C. F., Dirks, P., and Smalley, M. J.  Separating Stem Cells by Flow Cytometry:  Reducing Variability for Solid Tissues.  Cell Stem Cell, 5:  579-583, 2009.

Badders, N. M., Goel, S., Clark, R. J., Klos, K. S., Kim, S., Bafico, A., Lindvall, C., Williams, B. O., and Alexander, C. M.  The Wnt Receptor, Lrp5, Is Expressed by Mouse Mammary Stem Cells and Is Required to Maintain the Basal Lineage.  PLoS ONE, 4(8):e6594, 2009.

Domenech, M., Yu, H., Warrick, J., Badders, N. M., Meyvantsson, I., Alexander, C. M., and Beebe, D. J.  Cellular Observations Enabled by Microculture:  Paracrine Signaling and Population Demographics.  Integr. Biol., 1:  267-274, 2009.

Kim, Y. C., Clark, R. J., Pelegri, F., and Alexander, C. M.  Wnt4 Is Not Sufficient to Induce Lobuloalveolar Mammary Development.  BMC Dev. Biol. 9:55, 2009.

Alexander, C. M.  Base Behavior behind Budding Breasts:  Integrins and Mammary Stem Cell Activity.  Cell Stem Cell, 3:  5-6, 2008.

Badders, N. M., Yu, H., Alexander, C. M., and Beebe, D. J.  Quantification of Small Cell Numbers with a Microchannel Device.  BioTechniques, 45:  321-325, 2008.

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