Mary Helen Barcellos-Hoff

Biosketch / Results /

Mary Helen Barcellos-Hoff

Professor, Department of Radiation Oncology;Professor, Department of Cell Biology
Radiation Oncology

Contact Info

450 East 29th Street
New York, NY 10016



1986 — University of California, San Francisco (Experimental Pathology), Graduate Education
1986-1988 — University of California, Berkeley (Cell Bio and Biophysics), PostDoctoral Training

Research Interests

The goal of our research is to understand how tissues integrate information across multiple scales of organization and to use this information in modeling critical events in carcinogenesis. We study ionizing radiation (IR), a prototypic carcinogen, in terms of its effects on cell phenotype and tissue interactions. Identifying when and how tissue alterations contribute to the action of IR may provide a means to inhibiting its carcinogenic potential, as well as a better understanding of how normal tissues suppress carcinogenesis. A major focus of my laboratory is to study the multiple and complex mechanisms by which transforming growth factor beta (TGFb) affects irradiated cells and tissues. The combined effects of TGFb and IR have profound effects on epithelial phenotype, centrosome regulation and genomic stability. We discovered that TGFb is activated in response to IR, which in turn revealed that TGFb is essential for epithelial cells to mount the canonical DNA damage response as shown by the failure of Tgfb1 null murine epithelial cells to undergo cell cycle arrest or apoptosis in response to irradiation. We showed that the abrogated DNA damage response is due to regulation of ATM kinase activity and can be phenocopied using small molecule TGFb inhibitors in human epithelial cells. The requirement for TGFb in the genotoxic stress program also provides a previously unsuspected avenue to modulate radiotherapy. Pharmaceutical means to inhibit TGFb are in clinical trials. We have translated our discovery that TGFb ensures effective response to DNA damage by testing TGFI? inhibitors in preclinical human and mouse models of breast, brain and lung cancer. TGFb inhibition in conjunction with radiotherapy increases sensitivity to clonogenic death and tumor growth delay. A direct and specific requirement for TGFb in the genotoxic stress program provides an important vital link between cell fate and tissue integrity and underscores the dynamic interaction between target cells and other cell types. We developed a radiation chimera model to test this idea. In this model the mice are irradiated, then transplanted with unirradiated oncogenically primed mammary epithelial cells. Radiation accelerated tumorigenesis but surprisingly also affects the type of tumor, promoting those that are more aggressive basal-like phenotype. This model offers novel insight into the carcinogenic process.

Attenuation of the DNA Damage Response by Transforming Growth Factor-Beta Inhibitors Enhances Radiation Sensitivity of Non-Small-Cell Lung Cancer Cells In Vitro and In Vivo
Du, Shisuo; Bouquet, Sophie; Lo, Chen-Hao; Pellicciotta, Ilenia; Bolourchi, Shiva; Parry, Renate; Barcellos-Hoff, Mary Helen
2015-02-03; 0360-3016,International journal of radiation oncology biology physics - id: 1449062, year: 2015

Age- and Pregnancy-Associated DNA Methylation Changes in Mammary Epithelial Cells
Huh, Sung Jin; Clement, Kendell; Jee, David; Merlini, Alessandra; Choudhury, Sibgat; Maruyama, Reo; Yoo, Ronnie; Chytil, Anna; Boyle, Patrick; Ran, Fei Ann; Moses, Harold L; Barcellos-Hoff, Mary Helen; Jackson-Grusby, Laurie; Meissner, Alexander; Polyak, Kornelia
2015-02-02; 2213-6711,Stem cell reports - id: 1447452, year: 2015 JOURNAL ARTICLE

Development of a novel multiplexed assay for quantification of transforming growth factor-beta (TGF-beta)
Pellicciotta, Ilenia; Marciscano, Ariel E; Hardee, Matthew E; Francis, Derek; Formenti, Silvia; Barcellos-Hoff, Mary Helen
2015-01-19; 0897-7194,Growth factors - id: 1436282, year: 2015 JOURNAL ARTICLE

TGF-beta1 Protects Cells from Gamma-IR by Enhancing the Activity of the NHEJ Repair Pathway
Yi, Jae Youn; Kim, Mi-Ra; Lee, Jeeyong; An, You Sun; Jin, Yeong Bae; Park, In-Chul; Chung, Eunkyung; Shin, Incheol; Barcellos-Hoff, Mary Helen
2014-10-19; 1541-7786,Molecular cancer research - id: 1310212, year: 2014 JOURNAL ARTICLE

Densely Ionizing Radiation Acts via the Microenvironment to Promote Aggressive Trp53 Null Mammary Carcinomas
Illa-Bochaca, Irineu; Ouyang, Haoxu; Tang, Jonathan; Sebastiano, Christopher; Mao, Jian-Hua; Costes, Sylvain V; Demaria, Sandra; Barcellos-Hoff, Mary Helen
2014-10-13; 0008-5472,Cancer research - id: 1300252, year: 2014 JOURNAL ARTICLE