Our principle interests are to understand the role of microenvironment in mammary stem cell fate decisions in the contexts of aging and breast cancer. The vast majority of women diagnosed with breast cancer are aged over 50 years, and the tumors they bear are largely of a luminal subtype. The objectives of my research program are to generate a comprehensive understanding of the effects of the aging process on the normal human mammary gland and how these processes may contribute to breast tumor genesis. The cornerstone of our approach involves the use and characterization of a growing collection of normal human mammary epithelial cell (HMEC) strains, dubbed the HMEC Aging Resource, that was generated with my close collaborators Drs. Martha Stampfer and James Garbe. We explore the functional impact of aging on different lineages of HMEC by probing them with combinatorial bioengineered culture substrata and quantitative imaging analysis. In doing so, we are deriving a catalog of microenvironmental, epigenetic, genetic, and cellular changes that occur normally with age, and are trying to determine mechanistically how those changes increase the vulnerability of older women to breast cancer.
Self-organization is a dynamic and lineage-intrinsic property of mammary epithelial cells. Chanson L, Brownfield D, Garbe, JC, Kuhn I, Stampfer MR, Bissell MJ, and LaBarge MA. PNAS (2011), 108(8)3264-9.
The difficulty of targeting cancer stem cell niches. LaBarge MA. Clinical Cancer Research, Jun (2010), 16(12):3121-9.
Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments. LaBarge MA, Nelson CM, Villadsen R, Ruth J, Stampfer MM, Petersen OW, and Bissell MJ. Integrative Biology, Jan (2009).1(1):70-9 Epub 2008 Nov 12.