Dr Simon Richardson
Position: Clinical Research Associate
Personal home page:
Email:
ser32@cam.ac.uk
PubMed journal articles - click here
My research studies the stem cell biology and epigenetic dysregulation underlying aggressive B cell malignancies, focussing on B acute lymphoblastic leukaemia, the commonest cancer in children. Whilst it is treatable with chemotherapy in the majority of cases, patients who relapse or have certain genetic drivers have a very low survival rate and B-ALL remains one of the leading causes of death in childhood. Furthermore, survival rates from adult B-ALL remain poor. Using a combination of in vivo modelling, genome engineered cell lines, CRISPR screening and preclinical drug testing, my research is seeking to understand how mutations in epigenetic regulators generate this cancer and promote drug resistance, with the aim of using that knowledge to identify novel types of therapies for the most resistant cases.
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Nathalie Sakakini, Roy Straver, Dhoyazan M. A Azazi, Sarah J. Horton, Ryan Asby, Simon E. Richardson, Pedro Madrigal, Elizabeth J Soilleux, Rachael Bashford-Rogers, Jeroen de Ridder, Brian J. P Huntly. Mutational synergy with CREBBP loss in lymphomagenesis identified through forward insertional mutagenesis in a new DLBCL mouse model. (2024) doi.org/10.1101/2024.03.25.586554
Alicia Garcia-Gimenez, Jonathan E. Ditcham, Dhoyazan M.A. Azazi, Eshwar Meduri, Ryan Asby, Nathalie Sakakini, Cecile K. Lopez, Nisha Narayan, Tumas Beinortas, Jaana Bagri, Shuchi Agrawal Singh, George Giotopoulos, Michael P. Murphy, Sarah J. Horton, Brian J.P. Huntly* & Simon E. Richardson* Genetic or pharmacological inactivation of CREBBP sensitizes B-cell Acute Lymphoblastic Leukemia to Ferroptotic Cell Death upon BCL2 Inhibition. bioRxiv (2023) doi.org/10.1101/2023.10.02.556536 *Co-corresponding and senior author.
Garcia-Gimenez A & Richardson SE. The role of microenvironment in the initiation and evolution of B-cell precursor acute lymphoblastic leukemia. Frontiers in Oncology (2023) Vol13 doi.org/10.3389/fonc.2023.1150612
Wray JP, Deltcheva EM, Boiers C, Richardson SE, Chettri JB, Brown J, Gagrica S, Guo Y, Illendula A, Martens JHA, Stunnenberg HG, Bushweller JH, Nimmo R & Enver T. Regulome analysis in B-acute lymphoblastic leukemia exposes Core Binding Factor addiction as a therapeutic vulnerability. Nature Communications (2022) 13(1):7124. doi: 10.1038/s41467-022-34653-3.
Meduri E, Breeze C, Marando L, Richardson SE and Huntly BJP. The RNA editing landscape in Acute Myeloid Leukaemia reveals associations with disease mutations and clinical outcome. iScience (2022) doi.org/10.1016/j.isci.2022.105622
Chen HC et al LGR5 targeting molecules as therapeutic agents for multiple cancer types. bioRxiv (2022) doi: 10.1101/2022.09.01.506182
Peña OA, Lubin A, Rowell J, Hockings C, Jung J, Hoade Y, Dace P, Valdivia LE, Tuschl K, Boiers C, Virgilio M, Richardson SE and Payne EM. TLR7 ligation augments haematopoiesis in Rps14 (uS11) deficiency via paradoxical suppression of inflammatory signalling and enhanced differentiation. Blood Advances 2021. doi: 10.1182/bloodadvances.2020003055.
Richardson SE & Huntly BJP. Targeting Chromatin Regulation in Acute Myeloid Leukemia. HemaSphere. 2021. doi: 10.1097/hs9.0000000000000589
Pocock R, Farah N, Richardson SE, Mansour MR. Current and emerging therapeutic approaches for T-cell acute lymphoblastic leukaemia. Br J Haematol. 2021 May 3. doi: 10.1111/bjh.17310.
Richardson SE*, Ghazanfari R, Chhetri J, Enver T, Boiers C. In vitro differentiation of human pluripotent stem cells into the B lineage using OP9-MS5 co-culture. STAR Protoc. 2021;2(2):100420. *Lead & corresponding author
Leon T.E., Rapoz-D'Silva T., Bertoli C., Rahman S., Magnussen M., Philip B., Farah N., Richardson SE., Ahrabi S., Afonso Guerra-Assuncao J., Gupta R., Nacheva E.P., Henderson S., Herrero J., Linch D.C., de Bruin R.A.M. & Mansour M.R. EZH2 deficient T-cell acute lymphoblastic leukemia is sensitized to CHK1 inhibition through enhanced replication stress. Cancer Discovery. 2020; doi: 10.1158/2159-8290.CD-19-0789.
Richardson S.E.*, Brian D., Grandage V., Hough R., Kottaridis P., Mansour M., Payne E. & Khwaja A. Intensive chemotherapy is associated with poor overall survival in autoimmune disease-associated myeloid malignancies. HemaSphere. 2019;3(1):e164 *Corresponding author
Böiers C.*, Richardson S.E.*, Zriwil A., Turati V.A., Brown J., Wang D., Herrero J., Karlsson., Smith A.J.H., Jacobsen S.E.W. & Enver T. A human IPS model implicates embryonic B-myeloid fate restriction as a developmental susceptibility to B acute lymphoblastic leukemia-associated ETV6-RUNX1. Developmental Cell. 2018;44:362-377. *Equal contribution
Mathew NR, … Richardson S, … Zeiser R. Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD mutant leukemia cells. Nature Medicine. 2018;24:282-291.
Böiers C, Gupta R, Nimmo R, Richardson SE, Wray JP & Enver T. Novel oncogenetic pathways in ALL. Hematology Education: the education program for the annual congress of the European Hematology Association 2015;9:1-6
Richardson SE, Wagner T & McNamara C. The Role of Functional Imaging in Lymphoma: Current Controversies and Future Directions. Lymphoma and Chronic Lymphocytic Leukaemias. 2014;4:21-29.
Richardson SE, Khan I, Rawstron A, Sudak J, Edwards N, Verfuerth S, Fielding AK, Goldstone A, Kottaridis P, Morris E, Benjamin R, Peggs KS, Thomson KJ, Vandenberghe E, Mackinnon S, Chakraverty R. Risk-stratified adoptive cellular therapy following allogeneic hematopoietic stem cell transplantation for advanced chronic lymphocytic leukaemia. British Journal of Haematology. 2013;160(5):640-8.
Richardson SE. Modelling how initiating and transforming oncogenes cooperate to produce a leukaemic cell state. Disease Models and Mechanisms. 2013;6(1):3-5.
Richardson SE, Sudak J, Warbey V, Ramsay A & McNamara C. Routine bone marrow biopsy is not necessary in the staging of Hodgkin lymphoma (CHL) patients in the FDG-PET era. Leukaemia & Lymphoma. 2012; 53(3):381-5.
Richardson SE & McNamara C. The management of classical Hodgkin’s lymphoma: past, present and future. Advances in Haematology. 2011; 2011. 865870.
Richardson S, Cwynarski K, Hughes D, Malhotra A, Prentice A & McNamara C. Patients undergoing high dose chemotherapy for primary CNS lymphoma should receive prophylactic thiamine to prevent Wernike’s encephalopathy. Br. J. Haematol. 2010; 149:899-901.
Richardson S, Pallot D, Hughes T & Littlewood T. Improving the management of neutropenic sepsis in the emergency department. Br. J. Haematol. 2009; 144(4):617-8.
C-H. Yang, K-C.G. Jeng, W-H. Yang, Y-L. Chen, C-C. Hung, J-W. Lin, S. Richardson, C.R.H. Martin, M.J. Waring & L. Sheh. Unusually Strong Positive Cooperativity in Binding of Peptides to Latent Membrane Protein-1 DNA Fragments of the Epstein-Barr Viral Gene. ChemBioChem 2006; 7(8):1187-96.
