Mary Helen Barcellos-Hoff, PhD

Professor
Vice Chair of Research
Department of Radiation Oncology
+1 415 476-8091
Research Overview: 

Understanding the action of TGFβ in irradiated tissues and cells led us to define its role in genomic instability and a previously understudied role in the DNA damage response.  This led us to test whether TGFβ inhibition improve the response to radiotherapy, which substantiated its critical role in the irradiate tumor. 

  1. Bouquet, S.F., A. Pal, K.A. Pilones, S. Demaria, B. Hann, R.J. Akhurst, J.S. Babb, S.M. Lonning, J.K. DeWyngaert, S. Formenti, and M.H. Barcellos-Hoff. 2011. Transforming growth factor β1 inhibition increases the radiosensitivity of breast cancer cells in vitro and promotes tumor control by radiation in vivo. Clin Cancer Res. 17:6754-6765. PMID: 22028490
  2. Hardee, M.E., A.E. Marciscano, C.M. Medina-Ramirez, D. Zagzag, A. Narayana, S.M. Lonning, and M.H. Barcellos-Hoff. 2012. Resistance of Glioblastoma-Initiating Cells to Radiation Mediated by the Tumor Microenvironment Can Be Abolished by Inhibiting Transforming Growth Factor-β. Cancer Res. 72 (16):4119-29. PMC3724539  
  3. Kirshner, J., M.F. Jobling, M.J. Pajares, S.A. Ravani, A. Glick, M. Lavin, S. Koslov, Y. Shiloh, and M.H. Barcellos-Hoff. 2006. Inhibition of TGFb1 signaling attenuates ATM activity in response to genotoxic stress. Cancer Res. 66:10861-10868. PMID: 17090522
  4. Maxwell, C.A., M.C. Fleisch, S.V. Costes, A.C. Erickson, A. Boissiere, R. Gupta, S.A. Ravani, B. Parvin, and M.H. Barcellos-Hoff. 2008. Targeted and non-targeted effects of ionizing radiation that impact genomic instability. Cancer Res. 68:8304-8311. PMID:18922902

Radiation carcinogenesis is classically understood in terms of DNA damage and the potential increase in oncogenic mutations.  Based on our studies showing that radiation alters critical signaling and cell-cell interactions, we developed a radiation chimera mammary model that unequivocally demonstrates that radiation effects on the microenvironment strongly promote carcinogenesis.  Remarkably, the expression data from tumors arising in irradiated mice can be used to cluster cancers from irradiated humans and supports the contention that this mechanism of action contributes to radiation-preceded cancer in humans and that similar processes may underlie the origin of sporadic human cancers.

  1. Barcellos-Hoff, M.H., and S.A. Ravani. 2000. Irradiated mammary gland stroma promotes the expression of tumorigenic potential by unirradiated epithelial cells. Cancer Res. 60:1254-1260. PMID:10728684
  2. Nguyen, D.H., H.A. Oketch-Rabah, I. Illa-Bochaca, F.C. Geyer, J.S. Reis-Filho, J.H. Mao, S.A. Ravani, J. Zavadil, A.D. Borowsky, D.J. Jerry, K.A. Dunphy, J.H. Seo, S. Haslam, D. Medina, and M.H. Barcellos-Hoff. 2011. Radiation Acts on the Microenvironment to Affect Breast Carcinogenesis by Distinct Mechanisms that Decrease Cancer Latency and Affect Tumor Type. Cancer Cell. 19:640-651. PMC3110779
  3. Nguyen, D.H., E. Fredlund, W. Zhao, C.M. Perou, A. Balmain, J.-H. Mao, and M.H. Barcellos-Hoff. 2013. Murine Microenvironment Metaprofiles Associate with Human Cancer Etiology and Intrinsic Subtypes. Clin Cancer Res. 19:1353-1362.  PMC3732211
  4. Zhang, P., Lo, A., Huang, Y., Huang, G., Liang, G., Mott, J., Karpen, G.H., Blakely, E.A., Bissell, M.J. Barcellos-Hoff, M.H., Snijders, A.M., Mao, J.H.  Identification of genetic loci that control mammary tumor susceptibility through the host microenvironment. Sci Rep. 2015 Mar 9;5:8919. PMC4352890
Primary Thematic Area: 
Cancer Biology & Cell Signaling
Secondary Thematic Area: 
Developmental & Stem Cell Biology
Research Summary: 
Studies of radiation as carcinogen in breast, and its application as a cancer treatment using mouse models and human tissues and cell cultures.

Websites

Publications: 

Misrepair in Context: TGFß Regulation of DNA Repair.

Frontiers in oncology

Liu Q, Lopez K, Murnane J, Humphrey T, Barcellos-Hoff MH

Enhancing Career Paths for Tomorrow's Radiation Oncologists.

International journal of radiation oncology, biology, physics

Vapiwala N, Thomas CR, Grover S, Yap ML, Mitin T, Shulman LN, Gospodarowicz MK, Longo J, Petereit DG, Ennis RD, Hayman JA, Rodin D, Buchsbaum JC, Vikram B, Abdel-Wahab M, Epstein AH, Okunieff P, Goldwein J, Kupelian P, Weidhaas JB, Tucker MA, Boice JD, Fuller CD, Thompson RF, Trister AD, Formenti SC, Barcellos-Hoff MH, Jones J, Dharmarajan KV, Zietman AL, Coleman CN

Autocrine TGFß is a Survival Factor for Monocytes and Drives Immunosuppressive Lineage Commitment.

Cancer immunology research

Gonzalez-Junca A, Driscoll K, Pellicciotta I, Du S, Lo CH, Roy R, Parry R, Tenvooren I, Marquez D, Spitzer MH, Barcellos-Hoff MH

Subjugation of TGFß Signaling by Human Papilloma Virus in Head and Neck Squamous Cell Carcinoma Shifts DNA Repair from Homologous Recombination to Alternative End-Joining.

Clinical cancer research : an official journal of the American Association for Cancer Research

Liu Q, Ma L, Jones T, Palomero L, Pujana MA, Martinez-Ruiz H, Ha PK, Murnane J, Cuartas I, Seoane J, Baumann M, Linge A, Barcellos-Hoff MH

Evaluation of Radioresponse and Radiosensitizers in Glioblastoma Organotypic Cultures.

Methods in molecular biology (Clifton, N.J.)

Bayin NS, Ma L, Placantonakis DG, Barcellos-Hoff MH