Mary Helen Barcellos-Hoff, PhD
Professor, Department of Radiation Oncology, UCSF
My laboratory studies ionizing radiation, both as a carcinogen and a therapeutic. I discovered that radiation activates transforming growth factor β (TGFβ) and that TGFβ mediates DNA damage repair by homologous recombination, non-homologous end-joining and alternative end-joining. TGFβ also regulates the composition of the irradiated tumor microenvironment, particularly immune cell phenotypes. Detailed understanding of how TGFβ contributes to therapeutic response in preclinical models of breast, brain, lung and head and neck cancer has generated new rationales for clinical applications of TGFβ inhibitors.
In carcinogenesis, we use mouse models to study the mechanisms by which radiation increases breast cancer. Understanding the etiology of cancer is founded upon understanding of normal tissue biology and is advanced by application of systems biology approaches. We study the mammary gland in terms of stromal-epithelial interactions, regulation of mammary hierarchy and differentiation, and the functions of TGFβ and BRCA1. We have described radiation effects in cell-cell interactions, tissue composition and cell phenotype as a function of radiation type, dose and age at exposure in normal mammary gland and their consequences in carcinogenesis. These studies have generated new understanding of the biological mechanisms underlying radiation risks and insights for the means to protect irradiated populations after exposure.
University of Chicago, A.B., 1978, Biopsychology
University of California, San Francisco, Ph.D., 1986, Experimental Pathology
University of California, Berkeley, Postdoctoral training, 1988, Biophysics