Research Summary

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.

Research Funding

  • April 1, 2019 - March 31, 2024 - Definition of Immune Infiltrate Phenotype and DNA Damage Response Deficits Across Diverse Murine Mammary Carcinomas, Principal Investigator. Sponsor: NIH, Sponsor Award ID: R01CA239235
  • February 1, 2019 - January 31, 2024 - Reorienting the Glioblastoma Microenvironment to Respond to Immunotherapy, Principal Investigator. Sponsor: NIH/NINDS, Sponsor Award ID: R01NS109911
  • January 1, 2017 - December 31, 2020 - Dual benefit of TGFß inhibition on tumor control in the context of radiotherapy for breast cancer brain metastasis, Co-PI. Sponsor: DOD-BCRP, Sponsor Award ID: BC160513
  • July 1, 2015 - December 31, 2020 - Contribution of development and age to breast cancer etiology, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA190980

Education

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

Honors & Awards

  • 1982
    Basic Science Research Award, University of California, San Francisco
  • 1984
    Basic Science Research Award, University of California, San Francisco
  • 1984
    Student Travel Award, Radiation Research Society
  • 1986
    Student Travel Award, Radiation Research Society
  • 1985
    Student Travel Award, Cell Kinetics Society
  • 1986 - 1988
    NIH Fellowship Biophysics Training Grant, University of California, Berkeley
  • 2001
    Co-Chair, Mammary Gland, Gordon Research Conference
  • 2003
    Chair, Mammary Gland Gordon Research Conference
  • 2003 - 2008
    Susan Love MD Breast Cancer Foundation
  • 2003 – 2009
    NASA Radiation Discipline Working Group
  • 2006 - 2010
    Chief Scientist, DOE OBER Low Dose Program
  • 2012 - 2013
    Vice Chair, AACR Tumor Microenvironment Steering Committee
  • 2014
    Co-Chair, AACR 2014 Annual Meeting

Selected Publications

  1. Ma L, Gonzalez-Junca A, Zheng Y, Ouyang H, Illa-Bochaca I, Horst KC, Krings G, Wang Y, Fernandez-Garcia I, Chou W, Barcellos-Hoff MH Inflammation mediates the development of aggressive breast cancer following radiotherapy.  View on PubMed
  2. Barcellos-Hoff MH, Weaver VM In Memoriam - Zena Werb 1945-2020.  View on PubMed
  3. Gonzalez-Junca A, Reiners O, Borrero-Garcia LD, Beckford-Vera D, Lazar AA, Chou W, Braunstein S, VanBrocklin H, Franc BL, Barcellos-Hoff MH Positron Emission Tomography Imaging of Functional Transforming Growth Factor ß (TGFß) Activity and Benefit of TGFß Inhibition in Irradiated Intracranial Tumors.  View on PubMed
  4. Omene C, Ma L, Moore J, Ouyang H, Illa-Bochaca I, Chou W, Patel MS, Sebastiano C, Demaria S, Mao JH, Karagoz K, Gatza ML, Barcellos-Hoff MH Aggressive Mammary Cancers Lacking Lymphocytic Infiltration Arise in Irradiated Mice and Can Be Prevented by Dietary Intervention.  View on PubMed
  5. Liu Q, Lopez K, Murnane J, Humphrey T, Barcellos-Hoff MH Misrepair in Context: TGFß Regulation of DNA Repair.  View on PubMed
  6. 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 Enhancing Career Paths for Tomorrow's Radiation Oncologists.  View on PubMed
  7. Gonzalez-Junca A, Driscoll KE, Pellicciotta I, Du S, Lo CH, Roy R, Parry R, Tenvooren I, Marquez DM, Spitzer MH, Barcellos-Hoff MH Autocrine TGFß Is a Survival Factor for Monocytes and Drives Immunosuppressive Lineage Commitment.  View on PubMed
  8. 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 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.  View on PubMed
  9. Bayin NS, Ma L, Placantonakis DG, Barcellos-Hoff MH Evaluation of Radioresponse and Radiosensitizers in Glioblastoma Organotypic Cultures.  View on PubMed
  10. Bayin NS, Frenster JD, Sen R, Si S, Modrek AS, Galifianakis N, Dolgalev I, Ortenzi V, Illa-Bochaca I, Khahera A, Serrano J, Chiriboga L, Zagzag D, Golfinos JG, Doyle W, Tsirigos A, Heguy A, Chesler M, Barcellos-Hoff MH, Snuderl M, Placantonakis DG Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells.  View on PubMed
  11. Citrin DE, Prasanna PGS, Walker AJ, Freeman ML, Eke I, Barcellos-Hoff MH, Arankalayil MJ, Cohen EP, Wilkins RC, Ahmed MM, Anscher MS, Movsas B, Buchsbaum JC, Mendonca MS, Wynn TA, Coleman CN Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate. Report of an NCI Workshop, September 19, 2016.  View on PubMed
  12. Iizuka D, Sasatani M, Barcellos-Hoff MH, Kamiya K Hydrogen Peroxide Enhances TGFß-mediated Epithelial-to-Mesenchymal Transition in Human Mammary Epithelial MCF-10A Cells.  View on PubMed
  13. Mateo F, Arenas EJ, Aguilar H, Serra-Musach J, de Garibay GR, Boni J, Maicas M, Du S, Iorio F, Herranz-Ors C, Islam A, Prado X, Llorente A, Petit A, Vidal A, Català I, Soler T, Venturas G, Rojo-Sebastian A, Serra H, Cuadras D, Blanco I, Lozano J, Canals F, Sieuwerts AM, de Weerd V, Look MP, Puertas S, García N, Perkins AS, Bonifaci N, Skowron M, Gómez-Baldó L, Hernández V, Martínez-Aranda A, Martínez-Iniesta M, Serrat X, Cerón J, Brunet J, Barretina MP, Gil M, Falo C, Fernández A, Morilla I, Pernas S, Plà MJ, Andreu X, Seguí MA, Ballester R, Castellà E, Nellist M, Morales S, Valls J, Velasco A, Matias-Guiu X, Figueras A, Sánchez-Mut JV, Sánchez-Céspedes M, Cordero A, Gómez-Miragaya J, Palomero L, Gómez A, Gajewski TF, Cohen EEW, Jesiotr M, Bodnar L, Quintela-Fandino M, López-Bigas N, Valdés-Mas R, Puente XS, Viñals F, Casanovas O, Graupera M, Hernández-Losa J, Ramón Y Cajal S, García-Alonso L, Saez-Rodriguez J, Esteller M, Sierra A, Martín-Martín N, Matheu A, Carracedo A, González-Suárez E, Nanjundan M, Cortés J, Lázaro C, Odero MD, Martens JWM, Moreno-Bueno G, Barcellos-Hoff MH, Villanueva A, Gomis RR, Pujana MA Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.  View on PubMed
  14. Martinez-Ruiz H, Illa-Bochaca I, Omene C, Hanniford D, Liu Q, Hernando E, Barcellos-Hoff MH A TGFß-miR-182-BRCA1 axis controls the mammary differentiation hierarchy.  View on PubMed
  15. Bayin NS, Ma L, Thomas C, Baitalmal R, Sure A, Fansiwala K, Bustoros M, Golfinos JG, Pacione D, Snuderl M, Zagzag D, Barcellos-Hoff MH, Placantonakis D Patient-Specific Screening Using High-Grade Glioma Explants to Determine Potential Radiosensitization by a TGF-ß Small Molecule Inhibitor.  View on PubMed
  16. Formenti SC, Demaria S, Barcellos-Hoff MH, McBride WH Subverting misconceptions about radiation therapy.  View on PubMed
  17. Barcellos-Hoff MH, Mao JH HZE Radiation Non-Targeted Effects on the Microenvironment That Mediate Mammary Carcinogenesis.  View on PubMed
  18. Hendry JH, Niwa O, Barcellos-Hoff MH, Globus RK, Harrison JD, Martin MT, Seed TM, Shay JW, Story MD, Suzuki K, Yamashita S ICRP Publication 131: Stem cell biology with respect to carcinogenesis aspects of radiological protection.  View on PubMed
  19. Mittal V, El Rayes T, Narula N, McGraw TE, Altorki NK, Barcellos-Hoff MH The Microenvironment of Lung Cancer and Therapeutic Implications.  View on PubMed
  20. Barcellos-Hoff MH, Iliakis G, Jeggo P, McKenna G, O'Neil P, Wallace S "Praising What Is Lost. . .  View on PubMed

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