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).