Professor Paul Murray PhD

Professor Paul Murray

Department of Immunology and Immunotherapy
Professor of Molecular Pathology

Contact details

Address
Institute of Immunology and Immunotherapy
College of Medical and Dental Sciences

Professor Murray is currently Professor of Molecular Pathology in the Institute of Immunology and Immunotherapy at the University of Birmingham, United Kingdom. He runs a translational research programme which is investigating the pathogenesis of B cell malignancies with the overarching aim of developing novel therapies and improving outcomes for people with these tumours. This research programme is underpinned by over 2.5 million in live funding; including a 5 year Programme Grant from Bloodwise (formerly Leukaemia Lymphoma Research) the UK’s leading hematologic malignancy funder. He has published 112 original papers with an H-index of 53.

Qualifications

  • PhD Oncology 1996
  • MSc Distinction Biomedical Science 1992

Biography

During his PhD studies in the laboratory of Professor Lawrence Young at the University of Birmingham (1992-1996), Murray made several important contributions to the field, including the demonstration of unique patterns of virus latency in EBV-associated Hodgkin lymphoma (e.g. Murray et al., J Pathol; 1992) which subsequently led to the description of three epidemiologically and clinically distinct forms of EBV-associated Hodgkin’s lymphoma (e.g. Murray et al., Blood; 1999).

The impact of these studies was recognized by the award of a prestigious Louise Buchanan Fulbright Fellowship which funded Murray’s post-doctoral studies in the laboratory of Professor Richard Ambinder at the Johns Hopkins University Medical School, Baltimore.

This work led to three major papers, two of which (Murray et al., Blood; 1996, Murray et al., Blood; 1998) provided much of the underpinning evidence to support the use of cytotoxic T cells for the treatment of EBV-associated lymphomas, an approach which has since been shown to be highly successful in controlling post-transplant lymphomas.

In 2000 Murray set up his own laboratory in the Department of Pathology at the University of Birmingham and initiated studies on B cell lymphomas that contributed several important discoveries in the field, including: the first description of the c-FLIP-mediated anti-apoptotic phenotype in lymphoma (Dutton et al., PNAS 2003); the discovery of aberrant mTOR kinase activation in Hodgkin’s lymphoma  which subsequently led to the successful use of the mTOR inhibitor, everolimus, in the treatment of patients with relapsed Hodgkin’s lymphoma (Dutton et al., J Pathol 2005); and the identification of collagen receptor signalling as a mediator of chemotherapy resistance in lymphoma (Cader et al., Blood 2013).

Recently, The Murray lab’ has developed new in vitro systems which have allowed interrogation of the early steps in B cell lymphomagenesis (e.g. Vrzalikova et al., Blood 2011); studies which are already beginning to impact the design, discovery and pre‐clinical evaluation of therapeutic approaches to cure children with B cell lymphomas.

Teaching

  • Module leader: Genomics in cancer Pathology, MSc Genomic Medicine(two iterations per annum)
  • Module leader: The Molecular Pathology of Cancer, MSc Clinical Oncology
  • Module leader: Histopathology Module, BMedSci Clinical Sciences

As a member of the Institute Curriculum Development Committee I contribute to the development of cancer and biomedical teaching across the College. I remain an active and committed teacher, regularly giving lectures and tutorials (including the development of distance learning online tutorials) to undergraduate medical and science students, supervising BMedSci and Intercalating BMedSci Clinical Sciences project students in my lab’ and acting as personal tutor on the BMedSci and MBChB programmes. I am also the coordinator of a long-term successful Erasmus funded postgraduate student and staff exchange programme with the University of Palacky, Czech Republic.

Postgraduate supervision

I have supervised 12 PhD students to graduation. I currently supervise 6 PhD students, mentor 3 post‐doctoral fellows and regularly take undergraduate and Master’s project students.

PhD graduates have gone on to work in highly respected academic institutions or taken up senior positions in industry. For example, Victor Lopes is now running his own successful research group as Professor in the Institute of Genetics and Molecular Medicine at the University of Edinburgh; Yuk Ting Ma is Senior Lecturer in Clinical Oncology at the University of Birmingham, Gillian Davies is a Senior Scientist at Sagentia, and Zumla Cader has recently taken up a post-doctoral fellowship at the Dana Farber Cancer Institute, Harvard. In addition, a number of intercalated Clinical Sciences students who trained in my lab’ have taken up research fellowships in cancer research and in some cases already established themselves in independent academic positions.

For example, David Lissauer is now Clinical Lecturer in Obstetrics and Gynaecology at the University of Birmingham. I have served as general academic mentor providing advice to undergraduate science and medical students within and outside the University of Birmingham. My graduate students and post‐doctoral fellows have received a number of awards for the quality of their work, including the selection of their abstracts for oral presentations at international conferences (e.g. American Society for Hematology, International Symposium on EBV and Associated Diseases, International Symposium on Hodgkin lymphoma, Keystone Symposia: B cell Development and Function), travel scholarships (Royal Society, Leukaemia Lymphoma Research UK travelling fellowship, Kay Kendall Leukaemia Fund Travel Award; CRUK Travel Bursary) and prizes for best oral/poster presentations (e.g. FASEB lipid and lipid-regulated kinases; UK National Cancer Research Institute Annual Conference).

Research

The Murray lab’ addresses fundamental mechanisms of B cell lymphomagenesis with the overarching objective of improving outcomes for patients with these tumours. It is focussed around a 5 year LLR-funded Programme grant (January 2014-).. The major objectives of this Programme grant are to;

1) Investigate using primary B cell models how aberrant lyosophospholipid and collagen receptor signalling contribute to the early stages of lymphomagenesis and using cells isolated from primary tumour tissues explore how they influence the lymphoma microenvironment.

2) Study using animal models how these signalling pathways can be therapeutically targeted

3) Determine using tissue and serum from already assembled patient cohorts if alterations in these pathways can be used to predict both clinical outcomes and the response to therapies designed to reverse this aberrant signalling in patients. 

Other activities

Leadership in the research area is recognized by frequent requests to:

  • review programme, project, and fellowship grant applications (e.g. for Leukaemia Lymphoma Research UK, Cancer Research UK, including the New Agents Committee, UK Medical Research Council, Wellcome Trust, BBSRC);
  • Murray sits on scientific review panels (e.g. UK Children’s Cancer and Leukaemia Group, German Research Foundation (DFG), Grant Agency of the Czech Republic, Dutch Cancer Society, Research Grants Council of Hong Kong, and;
  • writes leading reviews in the field (e.g. Murray et al., Nature Reviews Cancer 2016, in press).

Murray reviews primary research papers for over 20 leading journals (e.g. Nature Medicine, Blood, Oncogene, Cancer Research, American Journal of Pathology).

He has served on the American Society of Haematology Hodgkin lymphoma scientific review panel, the editorial board of the Journal of Pathology, and on international search committees for professorial appointments (e.g. Chinese University of Hong Kong).

He is regularly invited to give talks and chair sessions at national and international conferences..

Publications

Recent publications

  1. Wragg JW, Finnity JP, Anderson JA, Ferguson HJM, Porfiri E, Bhatt RI, Murray PG, Heath VL, Bicknell R. Melanoma cell adhesion molecule is a vascular target in renal cancer. Cancer Res 2016, in press.
  2. Ford CA, Petrova S, Pound JD, Melville L, Paterson M, Ogden CA, Farnworth S, Dumitriu IE, Dunbar DR, Ruckerl D, Allen J, Hume DA, van Rooijen N, Murray PG, Freeman T, Gregory CD. Oncogenic properties of apoptotic tumor cells in aggressive B-cell lymphoma Current Biol 2015; 25: 577-88.
  3. Oldreive CE, Skowronska A, Davies NJ, Parry H, Agathanggelou A, Krysov S, Packham G, Rudzki Z, Cronin L, Vrzalikova K, Murray P, Odintsova E, Pratt G, Taylor AM, Moss P, Stankovic T. T-cell number and subtype influence the disease course of primary chronic lymphocytic leukaemia xenografts in alymphoid mice. Dis Model Mech. 2015 Aug 20. pii: dmm.021147. [Epub ahead of print]
  4. Palser AL, Grayson NE, White RE, Corton C, Correia S, Ba Abdullah MM, Watson SJ, Cotten M, Arrand JR, Murray PG, Allday M, Rickinson AB, Young LS, Farrell  PJ, Kellam P. Genome diversity of Epstein-Barr virus from multiple tumour types and normal infection. J Virol 2015; 89: 5222-37
  5. Saeed AA, Sims AH, Prime SS, Paterson I, Murray PG, Lopes VR. Gene expression profiling reveals biological pathways responsible for phenotypic heterogeneity between UK and Sri Lankan oral squamous cell carcinomas. Oral Oncol 2015; 51: 237-46.
  6. Yap L-F, Velapasamy S, Lee H-M, Thavaraj S, Pathmanathan R, Wei W, Vrzalikova K, Khoo A, Tsao S-W, Paterson I, Taylor G, Dawson C, Murray PG. Downregulation of LPA receptor 5 contributes to aberrant LPA signalling in EBV-associated nasopharyngeal carcinoma. J Pathol 2015; 235: 456-65.
  7. Mohamed G, Vrzalikova K, Cader Z, Vockerodt M, Nagy E, Flodr P, Yap L-F, Diepstra A, Kluin PM , Rosati S, Murray PG. Epstein-Barr virus, the germinal centre and the development of Hodgkin lymphoma. J Gen Virol, 2014; 95: 1861-1869.
  8. Cader FZ, Vockerodt M, Bose S, Nagy E, Brundler M-A, Kearns P, Murray PG. The EBV oncogene LMP1 protects lymphoma cells from cell death through the collagen mediated activation of DDR1. Blood 2013 122; 4237-4245. SUBJECT OF BLOOD EDITORIAL- Carbone A, Gloghini A. Activated DDR1 increases RS cell survival. Blood 2013; 122: 4152-4.
  9. Smith N, Tierney R, Wei W, Vockerodt M, Murray PG, Woodman CB, Rowe M. Induction of interferon-stimulated genes on the IL-4 response axis by Epstein-Barr virus infected human B cells; relevance to cellular transformation. PLoS One 2013; 8: e64868
  10. Vockerodt M, Wei W, Nagy E, Prouzova Z, Schrader A, Kube D, Rowe M, Woodman CB, Murray PG. Suppression of the LMP2A target gene, EGR-1, protects Hodgkin’s lymphoma cells from entry to the EBV lytic cycle. J Pathol 2013; 230: 399-409.
  11. van Roekel EH, Cheng, K, James ND, Wallace D, Michael A, Billingham LJ, Murray PG, Bryan RT, Zeegers MP. Smoking is associated with lower age, higher grade, higher stage, and larger size of malignant bladder tumours at diagnosis. Int J Cancer 2013; 133: 446-54.
  12. White RE, Ramer PC, Naresh KN, Meixlsperger S, Pinaud L, Rooney C, Savoldo B, Bodor C, Gribben J, Ibrahim HA, Bower M, Nourse J, Gandhi M, Middeldorp J, Cader Z, Murray PG, Munz C, Allday MJ. EBNA3B-deficient EBV promotes B cell lymphomagenesis in humanized mice and is found in human tumours. J Clin Invest 2012; 122: 1487-502.
  13. Leonard S, Gordon N, Smith N, Rowe M, Murray PG, Woodman CB. Arginine methyltransferases are regulated by Epstein-Barr virus in B cells and differentially expressed in Hodgkin’s lymphoma. Pathogens 2012; 1(1): 52-64.
  14. Wang Z, Li L, Su X, Gao Z, Srivastava G, Murray PG, Ambinder RF, Tao Q. Epigenetic silencing of the 3p22 tumor suppressor DLEC1 by promoter CpG methylation in non-Hodgkin and Hodgkin lymphomas. J Trans Med 2012; 11; 10:209.
  15. Vrzalikova K, Leonard S, Fan S, Bell A, Vockerodt  M, Flodr P, Wright K, Rowe M, Tao Q, Murray PG. Hypomethylation and over-expression of the beta isoform of BLIMP1 is induced by Epstein-Barr virus infection of B cells; potential implications for the pathogenesis of EBV-associated lymphomas. Pathogens 2012; 1(2): 83-101
  16. Hu C, Wei W, Chen X, Woodman CB, Yao Y, Nicholls J, Joab I, Sihota S, Shao J-Y, Derkaoui YD, Amari A, Maloney SL, Bell AI, Murray PG, Dawson CW, Young LS, Arrand JR. A global view of the oncogenic landscape in nasopharyngeal carcinoma: an integrated analysis at the genetic and expression levels. PLoS One 2012; 7: e41055
  17. Schrader A, Bentink S, Spang R, Lenze D, Hummel M, Kuo M, Arrand J, Murray PG, Trümper L, Kube D,  Vockerodt M. High Myc activity is an independent negative prognostic factor for diffuse large B cell lymphomas. Int J Cancer 2012; 131: E348-61
  18. Vrzalikova K, Vockerodt M, Leonard S, Bell A, Wei W, Schrader A, Wright KL, Kube D, Rowe M, Woodman CB, Murray PG. Down-regulation of BLIMP1α by the EBV oncogene LMP1 disrupts the plasma cell differentiation program and prevents viral replication in B cells: implications for the pathogenesis of EBV-associated B cell lymphomas. Blood 2011; 117: 5907-17. SUBJECT OF BLOOD EDITORIAL- Shirley CM, Ambinder RF. When differentiation goes viral. Blood 2011; 117: 5790-1.
  19. Leonard S, Wei W, Anderton J, Vockerodt M, Rowe M, Murray PG, Woodman CBJ. An investigation of the epigenetic and transcriptional changes which follow Epstein-Barr virus infection of germinal centre B cells and their relevance to the pathogenesis of Hodgkin’s lymphoma. J Virol 2011; 85: 9568-77
  20. Qiu J, Cosmopoulos K, Pegtel M, Hopmans E, Murray P, Middeldorp J, Shapiro M, Thorley-Lawson DA. A novel persistence associated EBV miRNA expression profile is disrupted in neoplasia. PLoS Pathogens 2011; 7: e1002193
  21. Lopes V, Murray P, Williams H, Woodman C, Watkinson J, Robinson M. Squamous cell carcinoma of the oral cavity rarely harbours oncogenic human papillomavirus. Oral Oncol 2011; 47: 698-701
  22. Bryan RT, Wei W, Shimwell NJ, Collins SI, Hussain SA, Billingham LJ, Murray PG, Deshmukh N, James ND, Wallace M, Johnson PJ, Zeegers MP, Cheng KK, Martin A, Ward DG. Assessment of High-Throughput High-Resolution MALDI-TOF-MS of Urinary Peptides for the Detection of Muscle-Invasive Bladder Cancer. Proteomics Clin Appl 2011; 5: 493-503
  23. Ma YT, Collins SI, Young LS, Murray PG, Woodman CBJ. Smoking initiation is followed by the early acquisition of epigenetic change: a longitudinal study. Br J Cancer 2011; 104: 1500-1504.
  24. Loughran ST, Campion EM, D'Souza BN, Smith SM, Vrzalikova K, Wen K, Murray PG, Walls D. Bfl-1 is a crucial pro-survival Nuclear Factor-κB target gene in Hodgkin/Reed-Sternberg cells. Int J Cancer 2011; 129: 2787-96
  25. Anderton JA, Bose S, Vockerodt M, Vrzalikova K, Wei W, Kuo M, Helin K, Christensen J, Rowe M, Murray PG, Woodman  CB. The H3K27me3 demethylase, KDM6B, is induced by Epstein-Barr virus and over-expressed in Hodgkin’s lymphoma Oncogene 2011; 30: 2037-43.
  26. Murray PG, Fan Y, Davies G, Ying J, Geng H, Ng KM, Li H, Gao Z, Kapatai G, Bose S, Anderton JA, Reynolds GM, Ito A, Woodman CBJ, Marafioti T, Ambinder RF, Tao Q. Epigenetic silencing of a proapoptotic cell adhesion molecule-the immunoglobulin superfamily member IGSF4 by promoter CpG methylation protects Hodgkin’s lymphoma cells from apoptosis. Am J Pathol 2010; 177: 1480-90.

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