UW madison
UW School of Medicine and Public Health
Carbone Cancer Center

Caroline M. Alexander, Ph.D.

Caroline M. Alexander
Professor of Oncology
Developmental Therapeutics - UW Carbone Cancer Center

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

6505 Wisconsin Institutes for Medical Research
Office - (608) 265-5182; Lab - (608) 262-1258
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
Selected Recent Publications: 


Kasza I, Adler D, Nelson DW, Eric Yen CL, Dumas S, Ntambi JM, MacDougald OA, Hernando D, Porter WP, Best FA, Alexander CM. Evaporative cooling provides a major metabolic energy sink. Mol Metab. 2019 Sep;27:47-61. doi: 10.1016/j.molmet.2019.06.023. Epub 2019 Jul 1. PubMed PMID: 31302039; PubMed Central PMCID: PMC6717770.


Alexander CM. The Wnt Signaling Landscape of Mammary Stem Cells and Breast Tumors. Prog Mol Biol Transl Sci. 2018 Jan;153:271-298. doi: 10.1016/bs.pmbts.2017.11.020. Epub 2017 Dec 27. PubMed PMID: 29389520.

Chute C, Yang X, Meyer K, Yang N, O'Neil K, Kasza I, Eliceiri K, Alexander C, Friedl A. Syndecan-1 induction in lung microenvironment supports the establishment of breast tumor metastases. Breast Cancer Res. 2018 Jul 5;20(1):66. doi: 10.1186/s13058-018-0995-x. PubMed PMID: 29976229; PubMed Central PMCID: PMC6034333.

Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, Poudel C, Sherman DS, Yu D, Arriola Apelo SI, Cottrell SE, Geiger G, Barnes ME, Wisinski JA, Fenske RJ, Matkowskyj KA, Kimple ME, Alexander CM, Merrins MJ, Lamming DW. Restoration of metabolic health by decreased consumption of branched-chain amino acids. J Physiol. 2018 Feb 15;596(4):623-645. doi: 10.1113/JP275075. Epub 2017 Dec 27. PubMed PMID: 29266268; PubMed Central PMCID: PMC5813603.

Finlin BS, Memetimin H, Confides AL, Kasza I, Zhu B, Vekaria HJ, Harfmann B, Jones KA, Johnson ZR, Westgate PM, Alexander CM, Sullivan PG, Dupont-Versteegden EE, Kern PA. Human adipose beiging in response to cold and mirabegron. JCI Insight. 2018 Aug 9;3(15). pii: 121510. doi: 10.1172/jci.insight.121510. [Epub ahead of print] PubMed PMID: 30089732; PubMed Central PMCID: PMC6129119.

Shea MP, O'Leary KA, Fakhraldeen SA, Goffin V, Friedl A, Wisinski KB, Alexander CM, Schuler LA. Antiestrogen Therapy Increases Plasticity and Cancer Stemness of Prolactin-Induced ERα(+) Mammary Carcinomas. Cancer Res. 2018 Apr 1;78(7):1672-1684. doi: 10.1158/0008-5472.CAN-17-0985. Epub 2018 Jan 23. PubMed PMID: 29363543; PubMed Central PMCID: PMC5882549.


Chin EN, Martin JA, Kim S, Fakhraldeen SA, Alexander CM. Lrp5 Has a Wnt-Independent Role in Glucose Uptake and Growth for Mammary Epithelial Cells. Mol Cell Biol. 2016 Dec 28(2015);36(6):871-85. doi: 10.1128/MCB.00800-15. PubMed PMID: 26711269; PubMed Central PMCID: PMC4810465.

Fontana L, Cummings NE, Arriola Apelo SI, Neuman JC, Kasza I, Schmidt BA, Cava E, Spelta F, Tosti V, Syed FA, Baar EL, Veronese N, Cottrell SE, Fenske RJ, Bertozzi B, Brar HK, Pietka T, Bullock AD, Figenshau RS, Andriole GL, Merrins MJ, Alexander CM, Kimple ME, Lamming DW. Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health. Cell Rep. 2016 Jul 12;16(2):520-30. doi: 10.1016/j.celrep.2016.05.092. Epub 2016 Jun 23. PubMed PMID: 27346343; PubMed Central PMCID: PMC4947548.

Kasza I, Hernando D, Roldan-Alzate A, Alexander CM, Reeder SB. Thermogenic profiling using magnetic resonance imaging of dermal and other adipose tissues. JCI Insight. 2016 Aug 18;1(13):e87146. doi: 10.1172/jci.insight.87146. PubMed PMID: 27668285; PubMed Central PMCID: PMC5034877.

Sikora MJ, Jacobsen BM, Levine K, Chen J, Davidson NE, Lee AV, Alexander CM, Oesterreich S. WNT4 mediates estrogen receptor signaling and endocrine resistance in invasive lobular carcinoma cell lines. Breast Cancer Res. 2016 Sep 20;18(1):92. doi: 10.1186/s13058-016-0748-7. PubMed PMID: 27650553; PubMed Central PMCID: PMC5028957.


Alexander CM, Kasza I, Yen CL, Reeder SB, Hernando D, Gallo RL, Jahoda CA, Horsley V, MacDougald OA. Dermal white adipose tissue: a new component of the thermogenic response. J Lipid Res. 2015 Nov;56(11):2061-9. doi: 10.1194/jlr.R062893. Epub 2015 Sep 24. PubMed PMID: 26405076; PubMed Central PMCID: PMC4617393.

Fakhraldeen SA, Clark RJ, Roopra A, Chin EN, Huang W, Castorino J, Wisinski KB, Kim T, Spiegelman VS, Alexander CM. Two Isoforms of the RNA Binding Protein, Coding Region Determinant-binding Protein (CRD-BP/IGF2BP1), Are Expressed in Breast Epithelium and Support Clonogenic Growth of Breast Tumor Cells. J Biol Chem. 2015 May 22;290(21):13386-400. doi: 10.1074/jbc.M115.655175. Epub 2015 Apr 10. PubMed PMID: 25861986; PubMed Central PMCID: PMC4505587.

Noubissi FK, Harkness T, Alexander CM, Ogle BM. Apoptosis-induced cancer cell fusion: a mechanism of breast cancer metastasis. FASEB J. 2015 Sep;29(9):4036-45. doi: 10.1096/fj.15-271098. Epub 2015 Jun 17. PubMed PMID: 26085132; PubMed Central PMCID: Policy Exempt – non-NIH funding.

Park HW, Kim YC, Yu B, Moroishi T, Mo JS, Plouffe SW, Meng Z, Lin KC, Yu FX, Alexander CM, Wang CY, Guan KL. Alternative Wnt Signaling Activates AP/TAZ. Cell. 2015 Aug 13;162(4):780-94. doi: 10.1016/j.cell.2015.07.013. PubMed PMID: 26276632; PubMed Central PMCID: PMC4538707.


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.

Kasza, I., Suh, Y., Wollny, D., Clark, R. J., Roopra, A., Colman , R. J., MacDougald, O. A., Shedd, T. A., Nelson, D. W., Yen, M.-I., Yen., C.-L. E., and Alexander, C. M.  Syndecan-1 Is Required to Maintain Intradermal Fat and Prevent Cold Stress.  PLoS Genet., 10(8):e1004514, 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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National Committees: 

Ad-Hoc service for National Institutes of Health: Molecular Oncology Study Section and National Institutes of Health: Basic Translational Special Emphasis Study Section

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