Caroline Alexander, PhD

Portrait of Caroline Alexander, PhD
Associate Professor
Oncology
Address: 
819A McArdle
1400 University Avenue
Madison, WI 53706
Telephone: 
(608) 265-5182
Focus Groups: 
Cancer Biology
Signal Transduction
Education: 
PhD, Cell Biology and Biochemistry, University of Kent, England
Postdoctoral research: Imperial Cancer Research Fund, London and UC-San Francisco
Research Summary: 
Mammary stem cells; Mouse mammary tumor models; Wnt signaling; Syndecan-1
Research Detail: 

We are studying aspects of mammary gland biology and neoplasia using transgenic mouse models. Our lab has two main foci. The first focus is to determine the molecular and cellular basis for Wnt-induced tumors. Particularly, we have found that Wnt signaling dysregulates mammary stem cells, and that this precedes the formation of tumors with mixtures of cells (that resemble human basaloid breast cancers). 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 Wnt signaling induces a plastic state of mammary cell differentiation that confers stem cell properties. Our analysis of the Wnt receptor, Lrp5, has shown that only specific Wnt signals work to induce and maintain adult mammary somatic stem cells. Our second focus is the elucidation of the mechanism for the generalized tumor resistance phenotype shown by mice with a mutation in the heparan sulfate proteoglycan, syndecan-1. This turns out to be a metabolic syndrome, and links syndecan-1 to lipid uptake, and lipid uptake to tumor susceptibility.

 

  • Current projects include:
  • Investigation of the molecular and cellular mechanism underlying the tumor resistance phenotype of mice with a mutation in the heparan sulfate proteoglycan, syndecan-1 (Sdc1) (McDermott et al., 2006; Suh, Kasza et al., in preparation).
  • Search for tumor drivers in a novel model of basaloid breast cancer (Kim et al., 2010; Kim et al., 2011).
  • Dissection of the Wnt signaling complexes that maintain mouse mammary stem cells (Badders et al., 2009; Goel et al., 2012).
  • Interrogation of the role of CRD-BP, an RNA binding protein, in the fate determination and tumorigenesis of mammary epithelia (collaboration with V. Spiegelman, Dermatology).
Selected Publications: 
Kasza I, Hernando D, Roldán-Alzate A, Alexander CM, Reeder SB.: Thermogenic profiling using magnetic resonance imaging of dermal and other adipose tissues. JCI Insight 1(13):e87146, 2016 Aug 18.
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 Research 18(1):92, 2016 Sep 20.
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 Reports 16(2):520-30, 2016 Jun 23.
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. Molecular and Cellular Biology 36(6):871-85, 2015 Dec 28
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. Journal of Lipid Research 56(11):2061-9, 2015 Sep 24.
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 YAP/TAZ. Cell 162(4):780-94, 2015 Aug 13.
Noubissi FK, Harkness T, Alexander CM, Ogle BM.: Apoptosis-induced cancer cell fusion: a mechanism of breast cancer metastasis. FASEB Journal 29(9):4036-45, 2015 Jun 17.
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. PLoS Genetics 2014 Aug 7.
Kasza I, Suh Y, Wollny D, Clark RJ, Roopra A, Colman RJ, MacDougald OA, Shedd TA, Nelson DW, Yen MI, Yen CL, Alexander CM.: Syndecan-1 is required to maintain intradermal fat and prevent cold stress. PLoS Genetics 10(8):e1004514, 2014 Aug 7.
Alexander CM, Joshi PA, Khokha R.: Fully interlocking: a story of teamwork among breast epithelial cells. Developmental Cell 28(2):114-5, 2014 Jan 27.