Caroline Alexander, PhD

Portrait of Caroline Alexander, PhD
Professor
Oncology
Address: 
6505 Wisconsin Institutes for Medical Research 2
1111 Highland Ave
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: 

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 cells

 

· 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 Publications: 
The Wnt Signaling Landscape of Mammary Stem Cells and Breast Tumors. Alexander CM. Prog Mol Biol Transl Sci. 2018 Jan;153:271-298. doi: 10.1016/bs.pmbts.2017.11.020. Epub 2017 Dec 27. PMID: 29389520
Antiestrogen Therapy Increases Plasticity and Cancer Stemness of Prolactin-Induced ERα+ Mammary Carcinomas. Shea MP, O'Leary KA, Fakhraldeen SA, Goffin V, Friedl A, Wisinski KB, Alexander CM, Schuler LA. Cancer Res. 2018 Apr 1;78(7):1672-1684. doi: 10.1158/0008-5472.CAN-17-0985. Epub 2018 Jan 23. PMID: 29363543
Restoration of metabolic health by decreased consumption of branched-chain amino acids. 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. J Physiol. 2018 Feb 15;596(4):623-645. doi: 10.1113/JP275075. Epub 2017 Dec 27. PMID: 29266268
Thermogenic profiling using magneticresonance imaging of dermal and other adipose tissues. Kasza I, Hernando D, Roldán-Alzate A, Alexander CM, Reeder SB. JCI Insight. 2016 Aug 18;1(13):e87146. doi: 10.1172/jci.insight.87146. PMID: 27668285
WNT4 mediates estrogen receptor signaling and endocrine resistance in invasive lobular carcinoma cell lines. Sikora MJ, Jacobsen BM, Levine K, Chen J, Davidson NE, Lee AV, Alexander CM, Oesterreich S. Breast Cancer Res. 2016 Sep 20;18(1):92. doi: 10.1186/s13058-016-0748-7. PMID: 27650553
Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health. 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. Cell Rep. 2016 Jul 12;16(2):520-530. doi: 10.1016/j.celrep.2016.05.092. Epub 2016 Jun 23. PMID: 27346343
Lrp5 Has a Wnt-Independent Role in Glucose Uptake and Growth for MammaryEpithelial Cells. Chin EN, Martin JA, Kim S, Fakhraldeen SA, Alexander CM. Mol Cell Biol. 2015 Dec 28;36(6):871-85. doi: 10.1128/MCB.00800-15. PMID: 26711269
Dermal white adipose tissue: a new component of the thermogenic response. Alexander CM, Kasza I, Yen CL, Reeder SB, Hernando D, Gallo RL, Jahoda CA, Horsley V, MacDougald OA. J Lipid Res. 2015 Nov;56(11):2061-9. doi: 10.1194/jlr.R062893. Epub 2015 Sep 24. Review. PMID: 26405076.
Alternative Wnt Signaling Activates YAP/TAZ. Park HW, Kim YC, Yu B, Moroishi T, Mo JS, Plouffe SW, Meng Z, Lin KC, Yu FX, Alexander CM, Wang CY, Guan KL. Cell. 2015 Aug 13;162(4):780-94. doi: 10.1016/j.cell.2015.07.013. PMID: 26276632.
Apoptosis-induced cancer cell fusion: a mechanism of breast cancer metastasis. Noubissi FK, Harkness T, Alexander CM, Ogle BM. FASEB J. 2015 Sep;29(9):4036-45. doi: 10.1096/fj.15-271098. Epub 2015 Jun 17. PMID: 26085132