Mary Helen Barcellos-Hoff

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Mary Helen Barcellos-Hoff

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

Contact Info

450 East 29th Street
New York, NY 10016


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.

The Microenvironment of Lung Cancer and Therapeutic Implications
Mittal, Vivek; El Rayes, Tina; Narula, Navneet; McGraw, Timothy E; Altorki, Nasser K; Barcellos-Hoff, Mary Helen. The Microenvironment of Lung Cancer and Therapeutic Implications. Advances in experimental medicine & biology. 2016 ;890:75-110 (1884342)

BUB1-bling over with Possibilities
Barcellos-Hoff, Mary Helen. BUB1-bling over with Possibilities. Neoplasia. 2015 Feb;17(2):153-154 (1494472)

Multiplexing TGF beta in the tumor microenvironment
Barcellos-Hoff, Mary Helen. Multiplexing TGF beta in the tumor microenvironment [Meeting Abstract]. Cancer research. 2015 JAN 1;75(1):?-? (1656342)

Concepts and challenges in cancer risk prediction for the space radiation environment
Barcellos-Hoff, Mary Helen; Blakely, Eleanor A; Burma, Sandeep; Fornace, Albert J Jr; Gerson, Stanton; Hlatky, Lynn; Kirsch, David G; Luderer, Ulrike; Shay, Jerry; Wang, Ya; Weil, Michael M. Concepts and challenges in cancer risk prediction for the space radiation environment. Life sciences in space research. 2015 Jul;6:92-103 (1720922)

The effect of environmental chemicals on the tumor microenvironment
Casey, Stephanie C; Vaccari, Monica; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Barcellos-Hoff, Mary Helen; Brown, Dustin G; Chapellier, Marion; Christopher, Joseph; Curran, Colleen; Forte, Stefano; Hamid, Roslida A; Heneberg, Petr; Koch, Daniel C; Krishnakumar, P K; Laconi, Ezio; Maguer-Satta, Veronique; Marongiu, Fabio; Memeo, Lorenzo; Mondello, Chiara; Raju, Jayadev; Roman, Jesse; Roy, Rabindra; Ryan, Elizabeth P; Ryeom, Sandra; Salem, Hosni K; Scovassi, A Ivana; Singh, Neetu; Soucek, Laura; Vermeulen, Louis; Whitfield, Jonathan R; Woodrick, Jordan; Colacci, Annamaria; Bisson, William H; Felsher, Dean W. The effect of environmental chemicals on the tumor microenvironment. Carcinogenesis. 2015 Jun;36 Suppl 1:S160-S183 (1640492)