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Caroline Alexander, Ph.D.

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AlexanderPhoto 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: 6505 Wisconsin Institutes for Medical Research
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

Alexander, C. M., Joshi, P. A., and Khokha, R.  Fully Interlocking:  A Story of Teamwork Among Breast Epithelial Cells.  Dev. Cell, 28(2):  114-115, 2014.

Berry, S. M., Chin, E. N., Jackson, S. S., Strotman, L. N., Goel, M., Thompson, N. E., Alexander, C. M., Miyamoto, S., Burgess, R. R., and Beebe, D. J.  Weak Protein-Protein Interactions Revealed by Immiscible Filtration Assisted by Surface Tension.  Anal. Biochem., 447: 133-140, 2014.

Kim, S., and Alexander, C. M.  Tumorsphere Assay Provides More Accurate Prediction of in Vivo Responses to Chemotherapeutics.  Biotechnol. Lett., 36(3): 481-488, 2014.

Harkness, T., Weaver, B. A., Alexander C. M., and Ogle, B. M.  Cell Fusion in Tumor Development:  Accelerated Genetic Evolution.  Crit. Rev. Oncog., 18(1-2):  19-42, 2013.

Smits, B. M. G., Haag, J. D., Rissman, A. I., Sharma, D., Tran, A., Schoenborn, A. A., Baird, R. C., Peiffer, D. S., Leinweber, D. Q., Muelbl, M. J., Meilahn, A. L., Eichelberg, M. R., Leng, N., Kendziorski, C., John, M. C., Powers, P. A., Alexander, C. M., and Gould M. N.  The Gene Desert Mammary Carcinoma Susceptibility Locus Mcs1a Regulates Nr2f1 Modifying Mammary Epithelial Cell Differentiation and Proliferation.  PLoS Genet., 9(6):e1003549, 2013.

Alexander, C. M., Goel, S., Fakhraldeen, S. A., and Kim, S.  Wnt Signaling in Mammary Glands:  Plastic Cell Fates and Combinatorial Signaling.  Cold Spring Harbor Perspect. Biol., 4(10):pii:a008037, 2012.

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., 287: 16454-16466, 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., 72: 3207-3216, 2012.

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

Klos, K. S., Kim, S., and Alexander, C. M.  Genotoxic Exposure during Juvenile Growth of Mammary Gland Depletes Stem Cell Activity and Inhibits Wnt Signaling.  PLoS One, 7(11):e49902, 2012.

Thliveris, A. T., Clipson, L., Sommer, L. L., Schoenike, B. A., Hasenstein, J. R., Schlamp, C. L., Alexander, C. M., Newton, M. A., Dove, W. F., and Amos-Landgraf, J. M.  Regulated Expression of Chromobox Homolog 5 Revealed in Tumors of ApcMin/+ ROSA11 Gene Trap Mice.  G3 (Bethesda), 2:  569-578, 2012.

Wang, Q., Yang, L., Alexander, C., and Temple, S.  The Niche Factor Syndecan-1 Regulates the Maintenance and Proliferation of Neural Progenitor Cells during Mammalian Cortical Development.  PLoS One, 7(8):e42883, 2012. [Erratum in:  PLoS One, 7(11), 2012.]

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