Gillies McKenna MD Ph.D.

Molecular Resistance to Treatments Group
The effects of radiation on cancer cells and on mechanisms of resistance to radiation with the goal of sensitizing cells to radiation by blocking mechanisms that control cell survival.

Prof Gillies McKenna

Tel  +44 (0)1865 617331
PA  Christel Turner
Email (PA) 
Contact address  Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford OX3 7DQ
Department  Department of Oncology
College Wolfson College

Research Summary

Professor McKenna’s research links basic science studies with translational-clinical applications. His research has focused on effects of radiation on cancer cells and on mechanisms of resistance to radiation with the goal of sensitizing cells to radiation by blocking mechanisms that control cell survival. Specifically he is interested in oncogenically activated signal transduction pathways that exert a radioprotective effect on tumour cells. His group has shown that the EGFR-Ras-PI3K-PTEN-Akt pathway appears to the major radioprotective pathway active in most solid tumours and this pathway then presents targets that could be manipulated in a clinical setting to modify the radiation response. His clinical interests are the treatment of lung cancer, soft tissue sarcomas, skin cancer, head and neck cancer, and melanomas.

Collaborators

Group Members

  • Dr Remko Prevo, Laboratory Manager
  • Dr Thomas Ashton, Postdoctoral Researcher
  • Cynthia Eccles, DPhil Student
  • Gagan Tiwana, DPhil Student
  • Giacomo Pirovano, DPhil Student

Collaborators

    Biography

    W. Gillies McKenna is Director of the Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology and Head of the Department of Oncology at the University of Oxford.

    Professor McKenna was born in Scotland. He received a Bachelor of Science in Zoology at the University of Edinburgh in 1972. He was a member of the Medical Scientist Training Programme at the Albert Einstein College of Medicine in New York and received his M.D. and Ph.D. in 1981. His Ph.D. thesis research investigated the cleavage patterns of DNA by mammalian endonucleases. Following an Internship in Medicine at the Johns Hopkins University Hospital and a Residency in Radiation Oncology at the National Cancer Institute. Dr. McKenna moved to the Department of Radiation Oncology at the University of Pennsylvania School of Medicine where he rose to become Chairman and Henry K. Pancoast Professor of Radiation Oncology. In 2005 he moved to his present position.

    He is the author of over 90 research articles and 40 editorials, reviews and chapters. He has edited a textbook on Clinical Oncology. He was the President of the Radiation Research Society and a member of the Board of Scientific Advisors for the National Cancer Institute. He was the 2005 recipient of the Association for Radiation Research Weiss Medal and is a Fellow of the Academy of Medical Sciences and the Royal College of Radiology.

    Professional Appointments
    2005 Professor
    Deptartment of Radiation Oncology and Biology
    University of Oxford

    1995-2005 Henry K Pancoast Professor
    Dept. of Radiation Oncology and Biology
    University of Pennsylvania School of Medicine

    1991-95 Henry K Pancoast Associate Professor
    Dept. of Radiation Oncology and Biology
    University of Pennsylvania School of Medicine

    1987-91 Assistant Professor
    Dept. of Radiation Oncology and Biology
    University of Pennsylvania School of Medicine

    1985-87 Assistant Professor of Radiology
    Dept. Radiology and Nuclear Medicine
    Uniformed Services University of Health Sciences

    1991-2005 Chairman
    Dept. Radiation Oncology
    University of Pennsylvania

    1987-2005 Staff Radiation Therapist
    Hospital of the University of Pennsylvania

    Awards Training and Qualifications

    • 1974, PhD Cell Biology, Albert Einstein College of Medicine, NY
    • 1974, MD, Albert Einstein College of Medicine, NY
    • 1968, BSc, University of Edinburgh

    Publications

    Selected Publications:

    Fokas E, Prevo R, Hammond EM, Brunner TB, McKenna WG, Muschel RJ. (2014) Targeting ATR in DNA damage response and cancer therapeutics. Cancer Treat Rev.4 Feb;40(1):109-17. doi: 10.1016/j.ctrv.2013.03.002. Epub 2013 Apr 11. Review.

    Fokas E, Eccles C, Patel N, Chu K-Y, Warren S, McKenna WG, Brunner TB. A treatment planning comparison of four target volume contouring guidelines for locally advanced pancreatic cancer radiotherapy. Radiotherapy and Oncology107(2):200-206 May 2013

    Fokas E, Eccles C, Patel N, Chu K-Y, Warren S, Gillies McKenna W, Brunner TB. Comparison of four target volume definitions for pancreatic cancer. Guidelines for treatment of the lymphatics and the primary tumor.. Strahlentherapie und Onkologie 189(5):407-416 May 2013

    Maughan T, Illidge T, Hoskin P, McKenna W, Brunner T, Mackay R, Oliver A, Young C, and Chan C (2010). Radiotherapy research priorities for the UK. Clin Oncology (R Coll Radiol), 22:707-9.

    Higgins G, Harris A, Prevo R, Helleday T, McKenna WG, and Buffa F (2010). Overexpression Of POLQ Confers a Poor Prognosis In Early Breast Cancer Patients. Oncotarget, 1(3):175-84.

    Yang J, Parsons J, Nicolay N, Caporali S, Harrington C, Singh R, Finch D, D'Atri S, Farmer P, Johnston P, McKenna W, Dianov G, and Sharma R (2010). Cells deficient in the base excision repair protein, DNA polymerase beta, are hypersensitive to oxaliplatin chemotherapy. Oncogene, 29(3):463-468.

    Higgins G, Prevo R, Lee Y, Helleday T, Muschel R, Taylor S, Yoshimura M, Hickson I, Bernhard E, and McKenna W (2010). A siRNA Screen of Genes Involved in DNA Repair Identifies Tumour Specific Radiosensitisation by POLQ Knockdown. Cancer Res, 70(7):2984-93.

    Al-Assar O, Muschel R, Mantoni T, McKenna WG, and Brunner T (2009). Radiation response of cancer stem-like cells from established human cell lines after sorting for surface markers.
    Int J Radiat Oncol Biol Phys, 75(4):1216-25.

    Qayum N, Muschel R, Im JH, Balathasan L, Koch C, Patel S, McKenna WG, and Bernhard E (2009). Tumor vascular changes mediated by inhibition of oncogenic signaling. Cancer Res, 69(15):6347-54.

    Parsons J, Tait P, Finch D, Dianova I, Edelmann M, Khoronenkova S, Kessler B, Sharma R, McKenna W, and Dianov G (2009). Ubiquitin ligase ARF-BP1/Mule modulates base excision repair. EMBO J 28:3207-15.

    Brunner T, Geiger M, Grabenbauer G, Lang-Welzenbach M, Mantoni T, Cavallaro A, Sauer R, Hohenberger W, and McKenna WG (2008). Phase I trial of the human immunodeficiency virus protease inhibitor nelfinavir and chemoradiation for locally advanced pancreatic cancer.
    J Clin Oncol, 26(16):2699-706.

    Prevo R, Deutsch E, Sampson O, Diplexcito J, Cengel K, Harper J, O'Neill P, McKenna WG, Patel S, and Bernhard E (2008). Class I PI3 kinase inhibition by the pyridinylfuranopyrimidine inhibitor PI-103 enhances tumor radiosensitivity. Cancer Res, 68(14):5915-23.

    Cengel K, Voong KR, Chandrasekaran S, Maggiorella L, Brunner T, Stanbridge E, Kao G, McKenna WG, and Bernhard E (2007). Oncogenic K-Ras signals through epidermal growth factor receptor and wild-type H-Ras to promote radiation survival in pancreatic and colorectal carcinoma cells. Neoplasia, 9(4):341-8.

    Cordes N, Frick S, Brunner T, Pilarsky C, Grutzmann R, Sipos B, Kloppel G, McKenna W, and Bernhard E (2007). Human pancreatic tumor cells are sensitized to ionizing radiation by knockdown of caveolin-1. Oncogene.

    Kim IA, Bae SS, Fernandes A, Wu J, Muschel R, McKenna WG, Birnbaum M, and Bernhard E (2005). Selective inhibition of Ras, phosphoinositide 3 kinase, and Akt isoforms increases the radiosensitivity of human carcinoma cell lines. Cancer Res, 65(17):7902-10.

    Finnberg N, Gruber J, Fei P, Rudolph D, Bric A, Kim SH, Burns T, Ajuha H, Page R, Wu GS, Chen Y, McKenna WG, Bernhard E, Lowe S, Mak T, and El-Deiry W (2005). DR5 knockout mice are compromised in radiation-induced apoptosis. Mol Cell Biol, 25(5):2000-13.

    Brunner T, Cengel K, Hahn S, Wu J, Fraker D, McKenna WG, and Bernhard E (2005). Pancreatic cancer cell radiation survival and prenyltransferase inhibition: the role of K-Ras.
    Cancer Res, 65(18):8433-41.

    Gupta A, Cerniglia G, Mick R, McKenna WG, and Muschel R (2005). HIV protease inhibitors block Akt signaling and radiosensitize tumor cells both in vitro and in vivo. Cancer Res, 65(18):8256-65.

    Cengel K, and McKenna W (2005). Molecular targets for altering radiosensitivity: lessons from Ras as a pre-clinical and clinical model. Crit Rev Oncol Hematol , 55(2):103-116.

    Fei P, Wang W, Kim Sh, Wang S, Burns T, Sax J, Buzzai M, Dicker D, McKenna WG, Bernhard E, and El-Deiry W (2004). Bnip3L is induced by p53 under hypoxia, and its knockdown promotes tumor growth. Cancer Cell, 6(6):597-609.

    Gupta A, Soto D, Feldman M, Goldsmith J, Mick R, Hahn S, Machtay M, Muschel R, and McKenna WG (2004). Signaling pathways in NSCLC as a predictor of outcome and response to therapy. Lung, 182(3):151-62.

    Martin N, Brunner T, Kiel K, DeLaney T, Regine W, Mohiuddin M, Rosato E, Haller D, Stevenson J, Smith D, Pramanik B, Tepper J, Tanaka W, Morrison B, Deutsch P, Gupta A, Muschel R, McKenna WG, Bernhard E, and Hahn S (2004). A phase I trial of the dual farnesyltransferase and geranylgeranyltransferase inhibitor L-778,123 and radiotherapy for locally advanced pancreatic cancer. Clin Cancer Res, 10(16):5447-54.

    Chaudhry MA, Chodosh L, McKenna WG, and Muschel R (2003). Gene expression profile of human cells irradiated in G1 and G2 phases of cell cycle. Cancer Lett, 195(2):221-33.

    Lee I, Glickson J, Dewhirst M, Leeper D, Burd R, Poptani H, Nadal L, McKenna WG, and Biaglow J (2003). Effect of mild hyperglycemia +/- meta-iodo-benzylguanidine on the radiation response of R3230 Ac tumors. Adv Exp Med Biol, 530:177-86.

    Brunner T, Gupta A, Shi Y, Hahn S, Muschel R, McKenna W, and Bernhard E (2003).
    Farnesyltransferase inhibitors as radiation sensitizers. Int J Radiat Biol, 79(7):569-76.

    Gupta A, Cerniglia G, Mick R, Ahmed M, Bakanauskas V, Muschel R, and McKenna WG (2003). Radiation sensitization of human cancer cells in vivo by inhibiting the activity of PI3K using LY294002. Int J Radiat Oncol Biol Phys, 56(3):846-53.

    Li B, Chang CM, Yuan M, McKenna WG, and Shu HK (2003). Resistance to small molecule inhibitors of epidermal growth factor receptor in malignant gliomas. Cancer Res, 63(21):7443-50.

    Kao G, McKenna WG, Guenther M, Muschel R, Lazar M, and Yen T (2003). Histone deacetylase 4 interacts with 53BP1 to mediate the DNA damage response. J Cell Biol, 160(7):1017-27.

    Kim I, Fernandes A, Wu J, Gupta A, Muschel R, McKenna W, and Bernhard E (2003).
    Selective inhibition of RAS signaling pathway increases the radiosensitivity in the wild type head & neck squamous cancer cell line with EGFR overexpression. Int J Radiat Oncol Biol Phys(57:S354).

    Bernhard E, Gupta A, Hahn S, Muschel R, and McKenna W (2003). Ras signaling and its inhibition with farnesyltransferase inhibitors: effects on radiation resistance and the tumor microenvironment. In Modification of Radiation Response: Cytokines, Growth Factors, and Other Biological Targets. Springer-Verlag:259-271.

    Bernhard E, Gupta A, Cohen-Jonathan E, Muschel R, Hahn S, and McKenna W (2003). Inhibiting signal transduction as an approach to radiosensitizing tumor cells. Oncogene-Directed Therapies:409-432.