Dr Simon Richardson

My research studies the stem cell biology and epigenetic dysregulation underlying aggressive B cell malignancies, focusing on B acute lymphoblastic leukaemia (B-ALL), 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 more efficacious and less toxic novel therapies for the most resistant cases.

Senior Clinical Research Associate; Honorary Consultant Haematologist

I studied Preclinical Medicine and Natural Sciences Pharmacology at the University of Cambridge, during which time I developed an interest in cancer research, graduating with a double first class degree in 2002. I completed my undergraduate clinical training at the University of Oxford and was awarded the George Pickering prize for best overall performance in clinical finals in 2005. After junior doctor rotations in Edinburgh and Oxford, I entered the academic haematology training programme at University College London/UCLH in 2009. I undertook a PhD at the UCL Cancer Institute, where I characterised and modelled a distinct wave of embryonic B-cell immune progenitors, which are likely cells of origin for childhood B-cell acute lymphoblastic leukaemia (B-ALL), the commonest cancer in childhood.

I moved to the Cambridge Stem Cell Institute in 2019 on CRUK-funded Clinician Scientist Fellowship, establishing a group investigating the stem cell biology and epigenetics of B-ALL, with a focus on developing novel drug combinations for B-ALL. In addition to my research, I work as an honorary consultant Haematologist on the bone marrow transplant and immunotherapy team at Addenbrookes hospital, and serve on the editorial board of the British Journal of Cancer and the NCRI ALL subgroup.

Sakakini N et al. Mutational synergy with CREBBP loss in lymphomagenesis identified through forward insertional mutagenesis in a new DLBCL mouse model. bioRxiv (2024) doi.org/10.1101/2024.03.25.586554

Garcia-Gimenez A … Huntly BJP & Richardson SE. 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.

Chen H. et al. Novel immunotherapeutics against LGR5 to target multiple cancer types. EMBO Molecular Medicine. 2024;16:2233-2261.

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;7;13:1150612.

Wray JP et al. Regulome analysis in B-acute lymphoblastic leukemia exposes Core Binding Factor addiction as a therapeutic vulnerability. Nature Communications. 2022;13(1):7124.

Meduri E…Richardson SE & Huntly BJP. The RNA editing landscape in Acute Myeloid Leukaemia reveals associations with gene expression, gene mutations and clinical outcome. iScience. 2022;25(12):105622.

Chen H. et al. Novel immunotherapeutics against LGR5 to target multiple cancer types. EMBO Molecular Medicine. 2024;16:2233-2261.Chen H. et al. Novel immunotherapeutics against LGR5 to target multiple cancer types. EMBO Molecular Medicine. 2024;16:2233-2261.Chen H. et al. Novel immunotherapeutics against LGR5 to target multiple cancer types. EMBO Molecular Medicine. 2024;16:2233-2261.

Peña OA … Richardson SE & Payne EM. TLR7 ligation augments haematopoiesis in Rps14 (uS11) deficiency via paradoxical suppression of inflammatory signalling and enhanced differentiation. Blood Advances. 2021;5(20): 4112–4124.

Richardson SE & Huntly BJP. Targeting Chromatin Regulation in high-risk AML. HemaSphere 2021;5(6):e589.

Richardson SE* et al. In vitro differentiation of human pluripotent stem cells into the B lineage using OP9-MS5 co-culture. STAR Protocols. 2021;2(2)100420. *Lead & corresponding author

Pocock R, Farah N, Richardson SE & Mansour MR. Current and Emerging Therapeutic Approaches for T-cell Acute Lymphoblastic Leukaemia. British Journal of Haematology. 2021;194(1):28-43.

Leon TE et al. EZH2 deficient T-cell acute lymphoblastic leukemia is sensitized to CHK1 inhibition through enhanced replication stress. Cancer Discovery. 2020;10(7):998-1017.

Beedham W et al. Head injury in the elderly – an overview for the physician. Clinical Medicine. 2019;9(2):177-184

Richardson SE* et al. Intensive chemotherapy is associated with poor overall survival in autoimmune disease-associated myeloid malignancies. HemaSphere. 2019;3(1):e164 *Corresponding author

Mathew NR et al. 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*, Richardson SE* et al. 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. *Joint first author, alphabetically listed

Böiers C et al. 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 et al. 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 et al. 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 et al. Improving the management of neutropenic sepsis in the emergency department. Br. J. Haematol. 2009; 144(4):617-8.

C-H. Yang et al. 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.

Member of the Royal College of Physicians; Fellow of the Royal College of Pathologists

2024