Ruth J Muschel MD Ph.D.

Mechanisms of Metastasis Group
Research group interested in the mechanisms underlying the development of metastasis.

Professor Ruth J Muschel

Email 
Tel  +44 (0)1865 225847
PA  Anne-Marie Honeyman-Tafa
Email (PA) 
Fax (PA)  +44 (0)1865 225209
Contact address  Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford OX3 7DQ
Department  Department of Oncology
College St Hilda's College

Research Summary

Despite surgery and/or radiation, many cancer patients, who appear to have localised disease, go on to develop distant metastases. My research group is interested in the mechanisms underlying the development of metastasis. We have used fluorescent microscopy to define the process of metastasis in the lung, finding adhesion of the tumour cells to the pulmonary blood vessels followed by spreading on the vasculature surface. Surviving cells give rise to early colonies formed within the blood vessels.

Some outstanding questions which we would like to answer are: What mechanisms do tumour cells use to arrest and survive at different metastatic organs? How do tumor cells interact with the host vasculature during metastasis? What are the mechanisms of metastasis to different organs, particularly the liver? Why does irradiation of the lung or tumour affect metastasis?

Collaborators

Group Members

  • Dr Ana Maria Gil-Bernabe, Postdoctoral Researcher
  • Dr Pavitra Kanaan, Postdoctoral Researcher
  • Dr JaeHong Im, Research Fellow
  • Dr Su Yin Lim Esther, Postdoctoral Researcher
  • Dr Chad McKee, Postdoctoral Researcher
  • Dr Thomas Tapmeier, Postdoctoral Researcher
  • Dr Bostjan Markelc, Postdoctoral Researcher (Marie Curie Fellow)
  • John Beech, Support Scientist
  • YunHong Cao, Laboratory Manager
  • Abul Siddiky, Clinical Research Fellow
  • Alex Gordon-Weeks, DPhil Student and Clinical Research Fellow
  • Serena Lucotti, DPhil Student
  • Arseniy Yushalin, DPhil Student
  • Ceren Yalaz, MSc Student
  • Jianzhou Chen, MSc Student

Collaborators

    Biography

    Awards Training and Qualifications

    • 1978, M.D. Ph.D., Albert Einstein College of Medicine, New York
    • 1972, B.A., Cornell University, Ithaca, NY

    Publications

    Selected Publications:

    Kelly CJ,  Hussien K, Fokas E, Kannan P, Shipley RJ, Ashton TM, Stratford M, Pearson N, Muschel RJ. Regulation of O(2) consumption by the PI3K and mTOR pathways contributes to tumor hypoxia. Radiother Oncol. 2014 Mar 13.

    Lunardi S, Muschel RJ, Brunner TB. The stromal compartments in pancreatic cancer: Are there any therapeutic targets? Cancer Lett. 2014 Feb 28;343(2):147-55.

    Hueting R, Kersemans V, Cornelissen B, Tredwell M, Hussien K, Christlieb M, Gee AD, Passchier J, Smart SC, Dilworth JR, Gouverneur V, Muschel RJ. A Comparison of the Behavior of 64Cu-Acetate and 64Cu-ATSM In Vitro and In Vivo. J  Nucl Med. 2014 Jan;55(1):128-34.

    Harada H, Inoue M, Itasaka S, Hirota K, Morinibu A, Shinomiya K, Zeng L, Ou G, Zhu Y, Yoshimura M, McKenna WG, Muschel RJ, Hiraoka M. Corrigendum: Cancer cells that survive radiation therapy acquire HIF-1 activity and translocate toward tumour blood vessels. Nat Commun. 2013 Oct 16;4:2314.

    Jae Hong Im and Ruth J Muschel: Brain Metastasis, In: Metastatic Cancer: Clinical and Biological Perspectives 2013 Aug 08

    Gil-Bernabé AM, Lucotti S, Muschel RJ. Coagulation and metastasis: what does the experimental literature tell us? Br J Haematol. 2013 Aug;162(4):433-41.

    Balathasan L, Beech JS, Muschel RJ. Ultrasonography-guided intracardiac injection: an improvement for quantitative brain colonization assays. Am J Pathol. 2013 Jul;183(1):26-34.

    McKee CM, Xu D, Kessler BM, Muschel RJ. Proteomic analysis reveals a proteolytic feedback loop in murine seminal fluid. Prostate. 2013 Jun 14.

    Lim SY, Gordon-Weeks AN, Zhao L, Tapmeier TT, Im JH, Cao Y, Beech J, Allen D, Smart S, Muschel RJ. Recruitment of myeloid cells to the tumor microenvironment supports liver metastasis. Oncoimmunology. 2013 Mar 1;2(3):e23187.

    Fokas E, Prevo R, Hammond EM, Brunner TB, McKenna WG, Muschel RJ. Targeting ATR in DNA damage response and cancer therapeutics. Cancer Treat Rev. 2013 Apr 11.

    Ferjancic S, Gil-Bernabé AM, Hill SA, Allen PD, Richardson P, Sparey T, Savory E, McGuffog J, Muschel RJ. VCAM-1 and VAP-1 recruit myeloid cells that promote pulmonary metastasis in mice. Blood. 2013 Apr 18;121(16):3289-97.

    Zhao L, Lim SY, Gordon-Weeks AN, Tapmeier TT, Im JH, Cao Y, Beech J, Allen D,  Smart S, Muschel RJ. Recruitment of a myeloid cell subset (CD11b/Gr1 mid) via CCL2/CCR2 promotes the development of colorectal cancer liver metastasis.  Hepatology. 2013 Feb;57(2):829-39.

    McKee CM, Xu D, Muschel RJ. Protease nexin 1: a novel regulator of prostate cancer cell growth and neo-angiogenesis. Oncotarget. 2013 Jan;4(1):1-2.

    Im, J.H., Tapmeier, T., Balathasan, L., Gal, A., Yameen, S., Hill, S., Smart, S., Noterdaeme, O., Kelly, M., Brady, M., Fu, W., Kruse, K., Bernhard, E.J., Augustin, H.G., and Muschel, R.J. (2013). 'G-CSF rescues tumor growth and neoangiogenesis during liver metastasis under host angiopoietin-2 deficiency'. Int J Cancer 132, 315-326.

     

    McKee, C.M., Xu, D., Cao, Y., Kabraji, S., Allen, D., Kersemans, V., Beech, J., Smart, S., Hamdy, F., Ishkanian, A., Sykes, J., Pintile, M., Milosevic, M., van der Kwast, T., Zafarana, G., Ramnarine, V.R., Jurisica, I., Mallof, C., Lam, W., Bristow, R.G., andMuschel, R.J. (2012). 'Protease nexin 1 inhibits hedgehog signaling in prostate adenocarcinoma'. J Clin Invest 122, 4025-4036.

    Gil-Bernabe, A.M., Ferjancic, S., Tlalka, M., Zhao, L., Allen, P.D., Im, J.H., Watson, K., Hill, S.A., Amirkhosravi, A., Francis, J.L., Pollard, J.W., Ruf, W., and Muschel, R.J. (2012). 'Recruitment of monocytes/macrophages by tissue factor-mediated coagulation is essential for metastatic cell survival and premetastatic niche establishment in mice'. Blood 119, 3164-3175.

    Fokas, E., Im, J.H., Hill, S., Yameen, S., Stratford, M., Beech, J., Hackl, W., Maira, S.M., Bernhard, E.J., McKenna, W.G., and Muschel, R.J. (2012). 'Dual inhibition of the PI3K/mTOR pathway increases tumor radiosensitivity by normalizing tumor vasculature'. Cancer Res 72, 239-248.

    Liu, S.K., Bham, S.A., Fokas, E., Beech, J., Im, J., Cho, S., Harris, A.L., and Muschel, R.J. (2011). 'Delta-like ligand 4-notch blockade and tumor radiation response'. J Natl Cancer Inst 103, 1778-1798.

    Xu, D., McKee, C.M., Cao, Y., Ding, Y., Kessler, B.M., and Muschel, R.J. (2010). 'Matrix metalloproteinase-9 regulates tumor cell invasion through cleavage of protease nexin-1'. Cancer Res 70, 6988-6998.

    Qayum, N., Muschel, R.J., Im, J.H., Balathasan, L., Koch, C.J., Patel, S., McKenna, W.G., and Bernhard, E.J. (2009). 'Tumor vascular changes mediated by inhibition of oncogenic signaling'. Cancer Res 69, 6347-6354

    Carbonell, W.S., Ansorge, O., Sibson, N., and Muschel, R.J. (2009). 'The vascular basement membrane as "soil" in brain metastasis'. PLoS One 4, e5857.

    Xu, D., Suenaga, N., Edelmann, M.J., Fridman, R., Muschel, R.J., and Kessler, B.M. (2008). 'Novel MMP-9 substrates in cancer cells revealed by a label-free quantitative proteomics approach'. Mol Cell Proteomics 7, 2215-2228.