Address: 819a McArdle Lab
Research InterestsAnalysis of breast development, signaling and disease
Cell Biology |
Human, mouse & rat
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.
J. Puchalski, K.S. Klos, N. Badders, L, Ailles, C.F. Kim, P. Dirks and
M.J. Smalley. Separating Stem Cells By Flow Cytometry: Reducing
Variability for Solid Tissues. Cell Stem Cell, 5: 579-580, 2009
Y.C. Kim, R.J. Clark, F. J. Pelegri and C.M. Alexander. Wnt4 is not sufficient to induce lobuloalveolar mammary development. BMC Dev. Biol., 9: 55, 2009
N.M. Badders, S. Goel, R. J. Clark, K.S. Klos, S. Kim, A. Bafico, C. Lindvall, B.O. Williams and C.M. Alexander. The Wnt Receptor, Lrp5, is Expressed by Mouse Mammary Stem Cells and is Required to Maintain the Basal Lineage. PLOS One, 4: e6594, 2009.
Y-C Kim, R.J. Clark, E.A. Ranheim and C.M. Alexander. Wnt1 expression induces short- and long-range cell recruitments that modify mammary tumor development, and are not induced by a cell-autonomous b-catenin effector. Cancer Res., 68: 10145-10153, 2008.
M. Mastroianni, Y.C. Kim, A. Esch and C.M. Alexander. Wnt Signaling can Substitute for Estrogen to Induce Division of ERa-positive Cells in a Mouse Mammary Tumor Model. Cancer Letts. 289: 23-31, 2010.