People

Professor Martin Dyer

Professor of Haemato-Oncology

School/Department: Leicester Cancer Research Centre

Telephone: +44 (0)116 229 7036

Email: mjsd1@le.ac.uk

Address: HWB, level 3, room 57

Profile

Martin Dyer initially studied Physiological Sciences at Worcester College, Oxford, where he obtained a first-class honours degree in 1977.  He then studied for a DPhil in the MRC Cellular Immunology lab in the Sir William Dunn School of Pathology in Oxford, under the supervision of Dr Simon Hunt, studying the expression of cell surface molecules on haemopoietic stem cells, using some of the first monoclonal antibodies produced in César Milstein’s lab (PMID: 6974759).

He then studied medicine at King’s College, Cambridge, graduating in January 1983.  After completing post-graduate medical training in Southampton (MRCP 1985), he returned to Cambridge to take up an MRC Clinical Fellowship under the supervision of Professor Frank Hayhoe in the department of Haematology.  Working closely with Drs Geoff Hale, Mike Clark and Professor Herman Waldmann, he assessed the efficacy of the CAMPATH series of rat monoclonal antibodies in patients with lymphoid malignancies (e.g. PMID 2713487, 27456733 and 2522881.)  This work led to the development of the first humanised antibody CAMPATH-1H or alemtuzumab (PMID: 2904526.)  He was awarded a Mere’s Senior Medical Fellowship at St John’s College in 1987.  During this time, he also characterised a number of novel lymphoma cell lines and began an interest in molecular cytogenetics (eg PMID: 2297573, 8324225, 8391614 and 2546634.)

In 1990 he was awarded the first Leukaemia Research Fund Bennett Senior Lectureship which he took up in Professor Daniel Catovsky’s group at the Institute of Cancer Research in London.  During his 11 years there his group demonstrated:

  1. Efficacy of alemtuzumab in T-cell prolymphocytic leukaemia, where it remains the standard of care PMID: 9215839
  2. Mutations of ATM in T-PLL, the first sporadic malignancy to be thus characterised PMID: 9288106.
  3. Molecular cloning of chromosomal translocations involving BCL9, BCL10 and BCL11 gene family from their involvement with the immunoglobulin heavy chain locus via long-distance inverse PCR, a technique developed in the lab by Dr Tony Willis PMID: 9310498, 9989495, 10910891.

In 1996-1997, he was Louise Buchanan Fulbright Fellow at the Department of Pathology, Stanford University CA.  He was a member of the International Lymphoma Study Group until 2010.

He moved to University of Leicester in 2001 to become Professor of Haemato-Oncology.  Here his focus was principally clinical, establishing the lymphoma and CLL clinics in the Leicester Royal Infirmary and then developing early phase and first-in-man clinical studies on the fabulous Hope Clinical Trial unit (PMID: 26542378.)  He was a member of the MRC Toxicology Unit in Leicester from 2002-2013, working closely with Professor Gerry Cohen and Dr Meike Vogler on mechanisms of apoptosis induced by BH3 mimetics, navitoclax and venetoclax, work that continues (eg PMID: 31601689.)  Proteomic and functional studies conducted in the MRC Toxicology Unit identified the role of the voltage-gated proton channel HVCN1 in B cell receptor signalling PMID: 20139987.

Currently, he works on novel antibodies in collaboration with Roche pharma and Isogenica along with studies on targeted small molecules for lymphoid malignancies in collaboration with a variety of companies.

 

Research

Professor Martin Dyer is director of the Ernest and Helen Scott Haematological Research Institute at the University of Leicester.

Research in the Ernest and Helen Scott Haematological Research Institute focusses on the assessment and development of new targeted therapies for lymphoid malignancies.  

A major strength of the group is the functional studies carried out on primary malignant cells. The group also has access to a unique collection of derived cell lines (and continue to generate new cell lines of biological interest) as well as generating unique patient-derived xenograft (PDX) models for which no cell lines currently exist, along with an extensive tissue bank of stored cells from patients with haematological malignancies.  These models, combined with their ability to perform reverse translational studies in patients on clinical trials allows unique insights into tumour biology.

There are two overlapping groups within the lab, one working on novel small molecules including BCL2 and BTK inhibitors and the other investigating T-cell redirecting bispecific antibodies (BsAbs).

Collectively their studies focus on mechanisms of action of these new therapeutics, defining mechanisms of inherent and acquired resistance, with the eventual aim of discovering synergistic combinations to take into the clinic. 

 

Publications

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Professor Martin Dyer has 307 publications (as of August 2022).

Citations = 31541.  H index = 95, i10index = 282 

CS Trethewey, HS Walter, ANM Alqahtani, R Schmid, DS Guttery, Y Griffin, MJ Ahearne, GS Saldanha, SPN Jayne, MJS Dyer. Limitations of monitoring disease progression using circulating tumor DNA in lymphoma: an example from primary cutaneous DLBCL leg-type. Hemasphere. 2022 Mar 1;6(3):e690.  https://doi.org/10.1097/HS9.0000000000000690  PMID: 35261967; PMCID: PMC8893288.

VM Smith, O Lomas, D Constantine, L Palmer, AH Schuh, D Bruce, O Gonchar, S Macip, S Jayne, MJS Dyer, TA Eyre. Dual dependence on BCL2 and MCL1 in T-cell prolymphocytic leukemia. Blood Adv. 2020 Feb 11;4(3):525-529. https://doi.org/10.1182/bloodadvances.2019000917  PMID: 32040552; PMCID: PMC7013268.

SA Rule, G Cartron, C Fegan, F Morschhauser, L Han, S Mitra, G Salles, MJS Dyer. Long-term follow-up of patients with mantle cell lymphoma (MCL) treated with the selective Bruton's tyrosine kinase inhibitor tirabrutinib (GS/ONO-4059). Leukemia. 2020 May;34(5):1458-1461. https://doi.org/10.1038/s41375-019-0658-7  PMID: 31827243; PMCID: PMC7192842.

HS Walter, CS Trethewey, MJ Ahearne, R Jackson, S Jayne, SD Wagner, G Saldanha, MJS Dyer. Successful treatment of primary cutaneous diffuse large B-cell lymphoma leg type with single-agent Venetoclax. JCO Precis Oncol. 2019 Dec;3:1-5. https://doi.org/10.1200/PO.19.00002  PMID: 35100690.

VM Smith, A Dietz, K Henz, D Bruecher, R Jackson, L Kowald, SJL van Wijk, S Jayne, S Macip, S Fulda, MJS Dyer, M Vogler. Specific interactions of BCL-2 family proteins mediate sensitivity to BH3-mimetics in diffuse large B-cell lymphoma. Haematologica. 2020 Aug;105(8):2150-2163. https://doi.org/10.3324/haematol.2019.220525  PMID: 31601689; PMCID: PMC7395267.

IW Flinn, JG Gribben, MJS Dyer, W Wierda, MB Maris, RR Furman, P Hillmen, KA Rogers, SP Lyer, A Quillet-Mary, L Ysebaert, HS Walter, M Verdugo, C Klein, H Huang, Y Jiang, G Lozanski, DS Pignataro, K Humphrey, M Mobasher, TJ Kipps. Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed/refractory chronic lymphocytic leukemia. Blood. 2019 Jun 27;133(26):2765-2775. https://doi.org/10.1182/blood-2019-01-896290  PMID: 30862645; PMCID: PMC6706803.

HS Walter, S Jayne, SA Rule, G Cartron, F Morschhauser, S Macip, L Karlin, C Jones, C Herbaux, P Quittet, N Shah, CV Hutchinson, C Fegan, Y Yang, S Mitra, G Salles, MJS Dyer. Long-term follow-up of patients with CLL treated with the selective Bruton's tyrosine kinase inhibitor ONO/GS-4059. Blood. 2017 May 18;129(20):2808-2810. https://doi.org/10.1182/blood-2017-02-765115 PMID: 28377400; PMCID: PMC5437828.

J Samuel, S Jayne, Y Chen, A Majid, A Wignall, T Wormull, H Najeeb, JL Luo, GD Jones, S Macip, MJS Dyer. Posttranscriptional upregulation of p53 by reactive oxygen species in chronic lymphocytic leukemia. Cancer Res. 2016 Nov 1;76(21):6311-6319. https://doi.org/10.1158/0008-5472.CAN-16-0843 Epub 2016 Sep 7. PMID: 27634759.

HS Walter, S Jayne, P Mensah, FM Miall, M Lyttelton, MJS Dyer. Obinutuzumab-induced coagulopathy in chronic lymphocytic leukaemia with trisomy 12. Blood Cancer J. 2016 Jun 17;6(6):e435. https://doi.org/10.1038/bcj.2016.42  PMID: 27315112; PMCID: PMC5141357.

EF Robles, M Mena-Varas, L Barrio, SV Merino-Cortes, P Balogh, MQ Du, T Akasaka, A Parker, S Roa, C Panizo, I Martin-Guerrero, R Siebert, V Segura, X Agirre, L Macri-Pellizeri, B Aldaz, A Vilas-Zornoza, S Zhang, S Moody, MJ Calasanz, T Tousseyn, C Broccardo, P Brousset, E Campos-Sanchez, C Cobaleda, I Sanchez-Garcia, JL Fernandez-Luna, R Garcia-Muñoz, E Pena, B Bellosillo, A Salar, MJ Baptista, JM Hernandez-Rivas, M Gonzalez, MJ Terol, J Climent, A Ferrandez, X Sagaert, AM Melnick, F Prosper, DG Oscier, YR Carrasco, MJS Dyer, JA Martinez- Climent. Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics. Nat Commun. 2016 Jun 14;7:11889. https://doi.org/10.1038/ncomms11889  PMID: 27297662; PMCID: PMC4911677.

HS Walter, SA Rule, MJS Dyer, L Karlin, C Jones, B Cazin, P Quittet, N Shah, CV Hutchinson, H Honda, K Duffy, J Birkett, V Jamieson, N Courtenay-Luck, T Yoshizawa, J Sharpe, T Ohno, S Abe, A Nishimura, G Cartron, F Morschhauser, C Fegan, G Salles. A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies. Blood. 2016 Jan 28;127(4):411-9. https://doi.org/10.1182/blood-2015-08-664086 PMID: 26542378; PMCID: PMC4731845.

J Samuel, S Macip, MJS Dyer. Efficacy of vemurafenib in hairy-cell leukemia. N Engl J Med. 2014 Jan 16;370(3):286-8. https://doi.org/10.1056/NEJMc1310849 PMID: 24428489.

HE Speedy, MC Di Bernardo, GP Sava, MJS Dyer, A Holroyd, Y Wang, NJ Sunter, L Mansouri, G Juliusson, KE Smedby, G Roos, S Jayne, A Majid, C Dearden, AG Hall, T Mainou-Fowler, GH Jackson, G Summerfield, RJ Harris, AR Pettitt, DJ Allsup, JR Bailey, G Pratt, C Pepper, C Fegan, R Rosenquist, D Catovsky, JM Allan, RS Houlston. A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia. Nat Genet. 2014 Jan;46(1):56-60. https://doi.org/10.1038/ng.2843 PMID: 24292274.

A Gewies, M Castineiras-Vilarino, U Ferch, N Jährling, K Heinrich, U Hoeckendorf, GK Przemeck, M Munding, O Groß, T Schroeder, M Horsch, EL Karran, A Majid, S Antonowicz, J Beckers, M Hrabé de Angelis, HU Dodt, C Peschel, I Förster, MJS Dyer, J Ruland. Prdm6 is essential for cardiovascular development in vivo. PLoS One. 2013 Nov 21;8(11):e81833. https://doi.org/10.1371/journal.pone.0081833 PMID: 24278461; PMCID: PMC3836774.

AB Alexandroff, V Shpadaruk, WM Bamford, DB Kennedy, R Burd, MJS Dyer. Alemtuzumab-resistant Sézary syndrome responding to zanolimumab. Br J Haematol. 2011 Aug;154(3):419-21. https://doi.org/10.1111/j.1365-2141.2011.08620.x Epub 2011 Apr 12. PMID: 21480857.

MJS Dyer, H Ye, PG Isaacson. Primary lymphoma-like lesions of the uterine cervix; sheep in wolves' clothing. Br J Haematol. 2011 Jun;153(6):791-4. https://doi.org/10.1111/j.1365-2141.2011.08659.x Epub 2011 Mar 16. PMID: 21410452.

E Mössner, P Brünker, S Moser, U Püntener, C Schmidt, S Herter, R Grau, C Gerdes, A Nopora, E van Puijenbroek, C Ferrara, P Sondermann, C Jäger, P Strein, G Fertig, T Friess, C Schüll, S Bauer, J Dal Porto, C Del Nagro, K Dabbagh, MJS Dyer, S Poppema, C Klein, P Umaña. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood. 2010 Jun 3;115(22):4393-402. https://doi.org/10.1182/blood-2009-06-225979 Epub 2010 Mar 1. PMID: 20194898; PMCID: PMC2881503.

M Capasso, MK Bhamrah, T Henley, RS Boyd, C Langlais, K Cain, D Dinsdale, K Pulford, M Khan, B Musset, VV Cherny, D Morgan, RD Gascoyne, E Vigorito, TE DeCoursey, IC MacLennan, MJS Dyer. HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species. Nat Immunol. 2010 Mar;11(3):265-72. https://doi.org/10.1038/ni.1843 Epub 2010 Feb 7. PMID: 20139987; PMCID: PMC3030552.

LJ Russell, M Capasso, I Vater, T Akasaka, OA Bernard, MJ Calasanz, T Chandrasekaran, E Chapiro, S Gesk, M Griffiths, DS Guttery, C Haferlach, L Harder, O Heidenreich, J Irving, L Kearney, F Nguyen-Khac, L Machado, L Minto, A Majid, AV Moorman, H Morrison, V Rand, JC Strefford, C Schwab, H Tönnies, MJS Dyer, R Siebert, CJ Harrison. Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. Blood. 2009 Sep 24;114(13):2688-98. https://doi.org/10.1182/blood-2009-03-208397 PMID: 19641190.

RS Boyd, R Jukes-Jones, R Walewska, D Brown, MJS Dyer, K Cain. Protein profiling of plasma membranes defines aberrant signalling pathways in mantle cell lymphoma. Mol Cell Proteomics. 2009 Jul;8(7):1501-15. https://doi.org/10.1074/mcp.M800515-MCP200 PMID: 19346216; PMCID: PMC2709182.

M Vogler, M Butterworth, A Majid, RJ Walewska, XM Sun, MJS Dyer, GM Cohen. Concurrent up-regulation of BCL-XL and BCL2A1 induces approximately 1000-fold resistance to ABT-737 in chronic lymphocytic leukemia. Blood. 2009 Apr 30;113(18):4403-13. https://doi.org/10.1182/blood-2008-08-173310 Epub 2008 Nov 13. PMID: 19008458.

T Akasaka, T Balasas, LJ Russell, KJ Sugimoto, A Majid, R Walewska, EL Karran, DG Brown, K Cain, L Harder, S Gesk, JI Martin-Subero, MG Atherton, M Brüggemann, MJ Calasanz, T Davies, OA Haas, A Hagemeijer, H Kempski, M Lessard, DM Lillington, S Moore, F Nguyen-Khac, I Radford-Weiss, C Schoch, S Struski, P Talley, MJ Welham, H Worley, JC Strefford, CJ Harrison, R Siebert, MJS Dyer. Five members of the CEBP transcription factor family are targeted by recurrent IGH translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Blood. 2007 Apr 15;109(8):3451-61. https://doi.org/10.1182/blood-2006-08-041012 Epub 2006 Dec 14. PMID: 17170124.

RS Boyd, PJ Adam, S Patel, JA Loader, J Berry, NT Redpath, HR Poyser, GC Fletcher, NA Burgess, AC Stamps, L Hudson, P Smith, M Griffiths, TG Willis, EL Karran, DG Oscier, D Catovsky, JA Terrett, MJS Dyer. Proteomic analysis of the cell-surface membrane in chronic lymphocytic leukemia: identification of two novel proteins, BCNP1 and MIG2B. Leukemia. 2003 Aug;17(8):1605-12. https://doi.org/10.1038/sj.leu.2402993 PMID: 12886250.

 
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Supervision

In the lab in the upcoming academic year (2022-23) there will be a total of seven PhD students, variously funded by the MRC DTP scheme (iCASE studentships in collaboration with Isogenica and TeleoNostix), the University of Leicester LPMI, Roche Pharma and the governments of Egypt and Saudi Arabia.
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