Life Sciences Division
My lab studies developmental pathways that govern proliferative potential in normal and abnormal human epithelial stem and progenitor cells. During its developmental cycle, the mammary gland displays many of the properties associated with tumor progression, such as re-initiation of proliferation, invasion, resistance to apoptosis, and angiogenesis. Importantly, due to its continual developmental nature, the mammary gland retains many of these properties throughout its lifetime. Thus, it is not surprising that many of the genes vital to the development of the mammary gland are also associated with tumorigenesis.
We are trying to elucidate the complex multicellular regulatory networks that control mammary gland development so that we can understand how environmental stressors that lead to cancer usurp these networks. A fundamental property of cancer cells, the capacity for extensive self-renewal, is only found in small subsets of cells found in normal somatic tissues – those with “stem” or “progenitor” qualities. In more differentiated cells, this property is repressed through epigenetic changes. Early events in carcinogenesis must either cause the expansion of pre-existing cells with extensive self-renewal potential or the acquisition of extensive self-renewal potential by cells that have repressed it. We are developing tissue specific risk models using human breast cells to determine the effects of prototypical carcinogens on the frequency of altered differentiation / self-renewal.