Caroline M. Alexander, PhD

Position title: Professor, Oncology

Email: alexander@oncology.wisc.edu

Phone: 608-265-5182

Organ System/Disease Focus:
Breast Cancer
Aligned Research Focus:
Mammary stem cells, mouse mammary tumor models, Wnt signaling, Syndecan-1
Caroline Alexander headshot

Pubmed

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Research Description:

Our lab is 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 dysregulation precedes the formation of differentiated, bilineal tumors. Wnt signaling is highly oncogenic to mammalian epithelia, and indeed comprises one of the main molecular sources of tumor initiation identified to date. We have recently found that Lrp5, a cell surface receptor described as a Wnt signaling receptor, has a metabolic function, serving to promote glucose uptake. This molecule is also essential to mammary stem cell function. We are working on the hypothesis that this glucose uptake activity of Lrp5 may be tumor promoting. Another major focus of our lab is to test the systemic effects of the mammalian thermogenic response. Particularly, we are testing whether altered skin-associated insulation can modify regenerative potential of organs and rates of tumor initiation.

Our current projects include:

  • Determination of the molecules that govern glucose uptake in mammary epithelial cell
  • Adaptations of metabolism in mammary stem cells
  • Investigating the function of Lrp5 in the cell surface presentation of glucose transporters
  • Evaluating the role of dermal white adipose tissue in regulating thermogenic activation
Selected References:
  • Kasza I, Hernando D, Roldán-Alzate A, Alexander CM, Reeder SB, 2016. Thermogenic profiling using magnetic resonance imaging of dermal and other adipose tissues. JCI Insight. Aug 18;1(13):e87146. PMCID: PMC5034877.
  • Chin EN, Martin JA, Kim S, Fakhraldeen SA, Alexander CM, 2015. Lrp5 Has a Wnt-Independent Role in Glucose Uptake and Growth for Mammary Epithelial Cells. Mol Cell Biol. Dec 28;36(6):871-85. PMCID: PMC4810465
  • Fakhraldeen SA, Clark RJ, Roopra A, Chin EN, Huang W, Castorino J, Wisinski KB, Kim T, Spiegelman VS, Alexander CM, 2015. 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. May 22;290(21):13386-400. PMCID: PMC4505587.
  • Kasza I, Suh Y, Wollny D, Clark RJ, Roopra A, Colman RJ, MacDougald OA, Shedd TA, Nelson DW, Yen MI, Yen CL, Alexander CM, 2014. Syndecan-1 is required to maintain intradermal fat and prevent cold stress. PLoS Genet, Aug;10(8):e1004514. PMCID: PMC4125098.
  • Goel S, Chin EN, Fakhraldeen SA, Berry SM, Beebe DJ, Alexander CM, 2012. Both LRP5 and LRP6 receptors are required to respond to physiological Wnt ligands in mammary epithelial cells and fibroblasts. J Biol Chem. May 11;287(20):16454-66. PMCID:PMC4810465