Professional background

Dr Marc Mansour is an honorary consultant haematologist at University College London Hospital and research group leader at the UCL Cancer Institute. He undertook his medical degree at the University of Edinburgh, medical training at King's College London and UCLH, followed by an MRC Clinical Research Training PhDship in the laboratory of Professors David Linch and Rosemary Gale at UCL, where he studied Notch signalling in acute leukaemia. He was funded by the Kay Kendell Leukemia Research Fund to undertake a travelling fellowship at Harvard Medical School and Dana-Farber Cancer Institute in Boston, USA. He was awarded the HMS Claudia Adams Barr Innovative Research award, and was a Harvard Medical School faculty member from 2012-2014. He is currently funded as a Bennett Senior Fellow by Bloodwise.

His research has focused on two aggressive haematological malignancies - T-cell acute lymphoblastic leukaemia (T-ALL) and acute myeloid leukaemia (AML). He has published extensively on the biology of acute leukaemia, authoring papers in Science, Nature, Nature Cell Biology, JCI, ELife, JCO and J Ex Med. His clinical interest is in ALL, AML and myelodysplasia (MDS).

Research interests

Dr Mansour has a long-standing interest in the biology of ALL and AML, particularly on the role of non-coding DNA in oncogene regulation. He has created several zebrafish models to study novel leukaemia oncogenes and tumour suppressors, with a particular focus on using these models to exploit the principal of synthetic lethality. This is based on the concept that, unlike normal cells, deficiency of tumour-suppressor genes in cancer cells creates a dependency on certain other genes for cell survival. Targeting these other genes with drugs should allow killing of tumour cells, while leaving normal cells unharmed.

Publications

  1. He S, Mansour MR, Zimmerman MW, Ki DH, Layden HM, Akahane K, Gjini E, de Groh ED, Perez-Atayde AR, Zhu S, Epstein JA, Look AT. Synergy between loss of NF1 and overexpression of MYCN in neuroblastoma is mediated by the GAP-related domain. eLife. 2016;5. PubMed PMID: 27130733. Pubmed Central PMCID: 4900799.
  2. Anderson NM, Li D, Peng HL, Laroche FJ, Mansour MR, Gjini E, Aioub M, Helman DJ, Roderick JE, Cheng T, Harrold I, Samaha Y, Meng L, Amsterdam A, Neuberg DS, Denton TT, Sanda T, Kelliher MA, Singh A, Look AT, Feng H. The TCA cycle transferase DLST is important for MYC-mediated leukemogenesis. Leukemia. 2016 Jun;30(6):1365-74. PubMed PMID: 26876595. Pubmed Central PMCID: 4889531.
  3. Mansour MR, Abraham BJ, Anders L, Berezovskaya A, Gutierrez A, Durbin AD, Etchin J, Lawton L, Sallan SE, Silverman LB, Loh ML, Hunger SP, Sanda T, Young RA, Look AT. Oncogene regulation. An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element. Science. 2014 Dec 12;346(6215):1373-7. PubMed PMID: 25394790.
  4. Etchin J, Montero J, Berezovskaya A, Le BT, Kentsis A, Christie AL, Conway AS, Chen WC, Reed C, Mansour MR, Ng CE, Adamia S, Rodig SJ, Galinsky IA, Stone RM, Klebanov B, Landesman Y, Kauffman M, Shacham S, Kung AL, Wang JC, Letai A, Look AT. Activity of a selective inhibitor of nuclear export, selinexor (KPT-330), against AML-initiating cells engrafted into immunosuppressed NSG mice. Leukemia. 2015 Jul 23. PubMed PMID: 26202935.
  5. Akahane K, Sanda T, Mansour MR, Radimerski T, DeAngelo DJ, Weinstock DM, Look AT. HSP90 inhibition leads to degradation of the TYK2 kinase and apoptotic cell death in T-cell acute lymphoblastic leukemia. Leukemia. 2015 Aug 12. PubMed PMID: 26265185.
  6. Lobry C, Oh P, Mansour MR, Look AT, Aifantis I. Notch signaling: switching an oncogene to a tumor suppressor. Blood. 2014 Apr 17;123(16):2451-9. PubMed PMID: 24608975. Pubmed Central PMCID: 3990910.
  7. Barcelo C, Etchin J, Mansour MR, Sanda T, Ginesta MM, Sanchez-Arevalo Lobo VJ, Real FX, Capella G, Estanyol JM, Jaumot M, Look AT, Agell N. Ribonucleoprotein HNRNPA2B1 interacts with and regulates oncogenic KRAS in pancreatic ductal adenocarcinoma cells. Gastroenterology. 2014 Oct;147(4):882-92 e8. PubMed PMID: 24998203.
  8. Li N, Fassl A, Chick J, Inuzuka H, Li X, Mansour MR, Liu L, Wang H, King B, Shaik S, Gutierrez A, Ordureau A, Otto T, Kreslavsky T, Baitsch L, Bury L, Meyer CA, Ke N, Mulry KA, Kluk MJ, Roy M, Kim S, Zhang X, Geng Y, Zagozdzon A, Jenkinson S, Gale RE, Linch DC, Zhao JJ, Mullighan CG, Harper JW, Aster JC, Aifantis I, von Boehmer H, Gygi SP, Wei W, Look AT, Sicinski P. Cyclin C is a haploinsufficient tumour suppressor. Nature cell biology. 2014 Nov;16(11):1080-91. PubMed PMID: 25344755. Pubmed Central PMCID: 4235773.
  9. Gjini E, Mansour MR, Sander JD, Moritz N, Nguyen AT, Kesarsing M, Gans E, He S, Chen S, Ko M, Kuang YY, Yang S, Zhou Y, Rodig S, Zon LI, Joung JK, Rao A, Look AT. A zebrafish model of myelodysplastic syndrome produced through tet2 genomic editing. Mol Cell Biol. 2015 Mar;35(5):789-804. PubMed PMID: 25512612. Pubmed Central PMCID: 4323485.
  10. Anderson NM, Harrold I, Mansour MR, Sanda T, McKeown M, Nagykary N, Bradner JE, Lan Zhang G, Look AT, Feng H. BCL2-specific inhibitor ABT-199 synergizes strongly with cytarabine against the early immature LOUCY cell line but not more-differentiated T-ALL cell lines. Leukemia. 2014 May;28(5):1145-8. PubMed PMID: 24342948. Pubmed Central PMCID: 4013222.
  11. Mansour MR, Reed C, Eisenberg AR, Tseng JC, Twizere JC, Daakour S, Yoda A, Rodig SJ, Tal N, Shochat C, Berezovskaya A, DeAngelo DJ, Sallan SE, Weinstock DM, Izraeli S, Kung AL, Kentsis A, Look AT. Targeting oncogenic interleukin-7 receptor signalling with N-acetylcysteine in T cell acute lymphoblastic leukaemia. Br J Haematol. 2015 Jan;168(2):230-8. PubMed PMID: 25256574. Pubmed Central PMCID: 4303513.
  12. Shochat C, Tal N, Gryshkova V, Birger Y, Bandapalli OR, Cazzaniga G, Gershman N, Kulozik AE, Biondi A, Mansour MR, Twizere JC, Muckenthaler MU, Ben-Tal N, Constantinescu SN, Bercovich D, Izraeli S. Novel activating mutations lacking cysteine in type I cytokine receptors in acute lymphoblastic leukemia. Blood. 2014 Jul 3;124(1):106-10. PubMed PMID: 24787007.
  13. Mansour MR, Sanda T, Lawton LN, Li X, Kreslavsky T, Novina CD, Brand M, Gutierrez A, Kelliher MA, Jamieson CH, von Boehmer H, Young RA, Look AT. The TAL1 complex targets the FBXW7 tumor suppressor by activating miR-223 in human T cell acute lymphoblastic leukemia. J Exp Med. 2013 Jul 29;210(8):1545-57. PubMed PMID: 23857984. Pubmed Central PMCID: 3727321. Epub 2013/07/17. eng.
  14. Etchin J, Sanda T, Mansour MR, Kentsis A, Montero J, Le BT, Christie AL, McCauley D, Rodig SJ, Kauffman M, Shacham S, Stone R, Letai A, Kung AL, Thomas Look A. KPT-330 inhibitor of CRM1 (XPO1)-mediated nuclear export has selective anti-leukaemic activity in preclinical models of T-cell acute lymphoblastic leukaemia and acute myeloid leukaemia. British journal of haematology. 2013 Apr;161(1):117-27. PubMed PMID: 23373539. Epub 2013/02/05. eng.
  15. Shepherd C, Banerjee L, Cheung CW, Mansour MR, Jenkinson S, Gale RE, Khwaja A. PI3K/mTOR inhibition upregulates NOTCH-MYC signalling leading to an impaired cytotoxic response. Leukemia. 2013 Mar;27(3):650-60. PubMed PMID: 23038273. Epub 2012/10/06. eng.
  16. Etchin J, Sun Q, Kentsis A, Farmer A, Zhang ZC, Sanda T, Mansour MR, Barcelo C, McCauley D, Kauffman M, Shacham S, Christie AL, Kung AL, Rodig SJ, Chook YM, Look AT. Antileukemic activity of nuclear export inhibitors that spare normal hematopoietic cells. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, UK. 2012 Jul 31. PubMed PMID: 22847027. Epub 2012/08/01. Eng.
  17. Jenkinson S, Koo K, Mansour MR, Goulden N, Vora A, Mitchell C, Wade R, Richards S, Hancock J, Moorman AV, Linch DC, Gale RE. Impact of NOTCH1/FBXW7 mutations on outcome in pediatric T-cell acute lymphoblastic leukemia patients treated on the MRC UKALL 2003 trial. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, UK. 2012 Jul 3. PubMed PMID: 22814294. Epub 2012/07/21. Eng.
  18. Mansour MR, Look AT. Discovery of a secreted tumor suppressor provides a promising therapeutic strategy for follicular lymphoma. Cancer Cell. 2011 Nov 15;20(5):559-61. PubMed PMID: 22094251. Epub 2011/11/19. eng.
  19. Gutierrez A, Grebliunaite R, Feng H, Kozakewich E, Zhu S, Guo F, Payne E, Mansour M, Dahlberg SE, Neuberg DS, den Hertog J, Prochownik EV, Testa JR, Harris M, Kanki JP, Look AT. Pten mediates Myc oncogene dependence in a conditional zebrafish model of T cell acute lymphoblastic leukemia. J Exp Med. 2011 Aug 1;208(8):1595-603. PubMed PMID: 21727187. Pubmed Central PMCID: 3149218. Epub 2011/07/06. eng.
  20. Mansour MR, Sulis ML, Duke V, Foroni L, Jenkinson S, Koo K, Allen CG, Gale RE, Buck G, Richards S, Paietta E, Rowe JM, Tallman MS, Goldstone AH, Ferrando AA, Linch DC. Prognostic implications of NOTCH1 and FBXW7 mutations in adults with T-cell acute lymphoblastic leukemia treated on the MRC UKALLXII/ECOG E2993 protocol. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2009 Sep 10;27(26):4352-6. PubMed PMID: 19635999. Pubmed Central PMCID: 2744275. Epub 2009/07/29. eng.
  21. Tosello V, Mansour MR, Barnes K, Paganin M, Sulis ML, Jenkinson S, Allen CG, Gale RE, Linch DC, Palomero T, Real P, Murty V, Yao X, Richards SM, Goldstone A, Rowe J, Basso G, Wiernik PH, Paietta E, Pieters R, Horstmann M, Meijerink JP, Ferrando AA. WT1 mutations in T-ALL. Blood. 2009;114(5):1038-45.
  22. Marks DI, Paietta EM, Moorman AV, Richards SM, Buck G, DeWald G, Ferrando A, Fielding AK, Goldstone AH, Ketterling RP, Litzow MR, Luger SM, McMillan AK, Mansour MR, Rowe JM, Tallman MS, Lazarus HM. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood. 2009 Dec 10;114(25):5136-45. PubMed PMID: 19828704. Pubmed Central PMCID: 2792210. Epub 2009/10/16. eng.
  23. Howe SJ, Mansour MR, Schwarzwaelder K, Bartholomae C, Hubank M, Kempski H, Brugman MH, Pike-Overzet K, Chatters SJ, de RD, Gilmour KC, Adams S, Thornhill SI, Parsley KL, Staal FJ, Gale RE, Linch DC, Bayford J, Brown L, Quaye M, Kinnon C, Ancliff P, Webb DK, Schmidt M, von KC, Gaspar HB, Thrasher AJ. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. JClinInvest. 2008;118(9):3143-50.
  24. Gordon WR, Roy M, Vardar-Ulu D, Garfinkel M, Mansour MR, Aster JC, Blacklow SC. Structure of the Notch1-negative regulatory region: implications for normal activation and pathogenic signaling in T-ALL. Blood. 2009;113(18):4381-90.
  25. Mansour MR. Oncogenic Kras and Notch-1 cooperate in T-cell acute lymphoblastic leukemia/lymphoma. Expert Rev Hematol. 2009 Apr;2(2):133-6. PubMed PMID: 21083447. Epub 2009/04/01. eng.
  26. Mansour MR, Duke V, Foroni L, Patel B, Allen CG, Ancliff PJ, Gale RE, Linch DC. Notch-1 mutations are secondary events in some patients with T-cell acute lymphoblastic leukemia. ClinCancer Res. 2007;13(23):6964-9.
  27. Maser RS, Choudhury B, Campbell PJ, Feng B, Wong KK, Protopopov A, O'Neil J, Gutierrez A, Ivanova E, Perna I, Lin E, Mani V, Jiang S, McNamara K, Zaghlul S, Edkins S, Stevens C, Brennan C, Martin ES, Wiedemeyer R, Kabbarah O, Nogueira C, Histen G, Aster J, Mansour M, Duke V, Foroni L, Fielding AK, Goldstone AH, Rowe JM, Wang YA, Look AT, Stratton MR, Chin L, Futreal PA, DePinho RA. Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers. Nature. 2007 Jun 21;447(7147):966-71. PubMed PMID: 17515920. Pubmed Central PMCID: 2714968. Epub 2007/05/23. eng.
  28. Mansour MR, Linch DC, Foroni L, Goldstone AH, Gale RE. High incidence of Notch-1 mutations in adult patients with T-cell acute lymphoblastic leukemia. Leukemia. 2006;20(3):537-9.
  29. Direkze S, Mansour M, Rodriguez-Justo M, Kibbler C, Gant V, Peggs KS. Candida kefyr fungal enteritis following autologous BMT. Bone marrow transplantation. 2012 Mar;47(3):465-6. PubMed PMID: 21625228. Epub 2011/06/01. eng.
  30. Mansour MR, Dogan A, Morris EC, Khwaja A, Linch DC, Mackinnon S, Peggs KS. Allogeneic transplantation for hepatosplenic alphabeta T-cell lymphoma. Bone Marrow Transplant. 2005;35(9):931-4.
  31. Mitry RR, Mansour MR, Havlik R, Habib NA. Gene therapy for liver tumours. AdvExpMedBiol. 2000;465:193-205.
  32. Mitry RR, Kelly MD, Zhao J, Negishi S, Mansour MR, Habib NA. p53 Plasmid Preparation and Techniques for Analysis of Gene Transfer and Expression. Methods in molecular medicine. 2000;45:207-20. PubMed PMID: 21341059.
  33. Havlik R, Sbisa E, Tullo A, Kelly MD, Mitry RR, Jiao LR, Mansour MR, Honda K, Habib NA. Results of resection for hilar cholangiocarcinoma with analysis of prognostic factors. Hepatogastroenterology. 2000;47(34):927-31.

GMC/GDC number: 4444307