Mary Helen Barcellos-hoff PhD

Dr. Barcellos-Hoff’s research focuses on how tissues integrate information across scales of organization and uses this information to identify critical events in terms of effects on cell phenotype and tissue interaction during radiation carcinogenesis. To assess the relevance of these effects, Dr. Barcellos-Hoff developed a novel model in which irradiated mice with transplanted, unirradiated ontogenically primed mammary epithelial cells. Host radiation both accelerates tumorigenesis and affects the type of tumor, promoting those that are more aggressive. This model offers novel insight into the carcinogenic process. Identifying which specific tissue alterations contribute to the action of IR may provide means to inhibit its carcinogenic potential, plus a better understanding of how tissues suppress carcinogenesis.

The main focus has been to understand the biology of transforming growth factor β (TGFβ), which is activated in irradiated cells and tissues, in normal mammary gland development and its contribution to radiation responses of tissues and tumors. In normal epithelial cells, TGFβ controls proliferation and mammary lineage commitment. In irradiated epithelial cells, TGFβ affects epithelial phenotypic stability, centrosome regulation, and genomic stability. Dr. Barcellos-Hoff’s laboratory demonstrated that TGFβ is essential for epithelial cells to mount the canonical DNA damage response. The requirement for TGFβ in the genotoxic stress program provides a link between cell fate and tissue integrity and underscores interaction between target cells and other cell types.

The requirement for TGFβ in the genotoxic stress program also provided a previously unsuspected avenue to modulate radiotherapy by using concurrent treatment with TGFβ inhibitors and radiation in preclinical breast, brain, and lung cancer models to increase radiation sensitivity and tumor control.