The Alexander Laboratory
Faculty > Caroline M. Alexander
Caroline M. Alexander
Associate Professor, Oncology
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Organ System/Disease Focus:Cancer Stem Cells
Aligned Research Focus: Mammary stem cells, mouse mammary tumor models, Wnt signaling, Syndecan-1
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 to elucidate how and when adult somatic stem cells can be recruited as tumor precursor cells. Current projects include:
- 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).
- Modeling of stem cell-based breast cancer.
- The activation of stromal cells and their recruitment to tumor development during Wnt-induced tumorigenesis.
- The analysis of adult stem cell responses during tumor initiation.
- Determination of how Wnt signaling supports normal mammary stem cell function.
- An investigation of cell-cell interactions in mammary gland, using micro channel cultures to identify endogenous growth promoting and inhibiting substances secreted by minor sub-populations.
Chen S, Zheng T, Shortreed MR, Alexander C, Smith LM. Analysis of cell surface carbohydrate expression patterns in normal and tumorigenic human breast cell lines using lectin arrays. Anal Chem. 79(15):5698-702. Epub 2007 Jun 20. 2007.