Dr John Riches

MA, BM BCh, MRCP, PhD, FRCPath, FHEA
Clinical Reader in Cancer Immuno-metabolism
Group Leader
Twitter
Research Focus

My major research interest is investigating the alterations in metabolism that accompany B-cell activation and how this is reflected in the metabolism of low- and high-grade lymphomas including chronic lymphocytic leukaemia/small lymphocytic lymphoma, diffuse large B cell lymphoma and Burkitt lymphoma. Our aim is that an enhanced understanding of the metabolism of normal and malignant B cells will underpin the development of the next generation of anti-metabolic drugs for these diseases. In addition, I am the course director for the MSc Cancer & Clinical Oncology Programme.

Key Publications

PHGDH is required for germinal center formation and is a therapeutic target in MYC-driven lymphoma. The Journal of Clinical Investigation (2022) 2;132(9):e153436. PMID: 35316216

B-cell Receptor Signaling Induced Metabolic Alterations in Chronic Lymphocytic Leukemia Can Be Partially Bypassed by TP53 Abnormalities. HemaSphere (2022) 6(6):e722. PMID: 35747847

Outcomes of patients with hematologic malignancies and COVID-19: A systematic review and meta-analysis of 3377 patients. Blood (2020) 136(25):2881-2892. PMID: 33113551

Trisomy 12 Chronic Lymphocytic Leukemia cells exhibit up-regulation of integrin signaling that is modulated by NOTCH1 mutations. Blood (2014) 123(26):4101-10. PMID: 24829201

T cells from CLL patients exhibit features of T-cell exhaustion but retain capacity for cytokine production. Blood (2013) 121(9):1612-21. PMID: 23247726

Major Funding
  • 2021-2024 - Barts Charity Project Grant, £266,437
  • 2020 - Wellcome Trust, £189,728
  • 2019 - Kay Kendall Leukaemia Fund, £217,498
  • 2016- Wellcome Trust Intermediate Clinical Fellowship, £863,503
Other Activities
  • 2020 - present: Member of NCRI Lymphoma Subgroup
  • 2019 - present: Member of UK CLL Forum Executive Committee
  • 2019-present: Member of Pan-London Haemato-oncology guidelines writing group
  • 2018-present: Course Director for the MSc Cancer & Clinical Oncology Programme
Research

My major research interest is investigating the alterations in metabolism that accompany B-cell activation and how this is reflected in the metabolism of low- and high grade lymphomas including chronic lymphocytic leukaemia/small lymphocytic lymphoma, diffuse large B cell lymphoma and Burkitt lymphoma. We use a variety of proteomic and metabolomic techniques to study these questions in primary patient samples, B-cell lines and murine conditional knockout and transgenic lymphoma models.  We are particularly interested in the impact of genetic aberrations of MYC and p53 on the metabolism of lymphoma cells and how this relates to high grade transformation of CLL (Richter syndrome). Our overall aim is that an enhanced understanding of the metabolism of normal and malignant B cells will underpin the development of the next generation of anti-metabolic drugs for these cancers and may also be of benefit in the treatment of non-malignant autoimmune conditions. In addition I am involved in teaching undergraduate and MSc students and am the course director for the MSc Cancer & Clinical Oncology Programme.

I combine my laboratory and translational research programme with clinical practice with the Cancer Centre at Barts Health, with specific emphasis on the treatment of lymphoid malignancies including CLL and lymphoma. In addition to my research in metabolism, I have a particular interest in the role of targeted therapies, immunotherapy and bone marrow transplantation in the treatment of these diseases.

External collaborators

Karen Vousden, The Francis Crick Institute, London, UK

Dinis Calado, The Francis Crick Institute, London, UK

James MacRae, The Francis Crick Institute, London, UK

Louisa James, The Blizzard Institute, QMUL, London, UK

Thomas Kipps, Moores Cancer Center, University of California, San Diego, USA

Laura Rassenti, Moores Cancer Center, University of California, San Diego, USA

Other Activities
  • 2020 - present: Member of NCRI Lymphoma Subgroup
  • 2019 - present: Member of UK CLL Forum Executive Committee
  • 2019-present: Member of Pan-London Haemato-oncology guidelines writing group
  • 2018-present: Course Director for the MSc Cancer & Clinical Oncology Programme
  • 2015-present: Fellow of the Royal College of Pathologists
  • 2012-present: Member of European Hematology Association
  • 2014-2015: Intercollegiate Committee on Haematology
  • 2014-2015: Trainees Advisory Committee Representative
  • 2013-2015: UK CLL Forum Executive Committee
Major Funding
  • 2021-2024 - Barts Charity Project Grant, £266,437
  • 2020 - Wellcome Trust, £189,728
  • 2020 - Barts Charity, £29,838
  • 2019 - Kay Kendall Leukaemia Fund, £217,498
  • 2019 - Greg Wolf Leukaemia Fund, £22,000
  • 2016- Wellcome Trust Intermediate Clinical Fellowship, £863,503
  • 2009 - Cancer Research UK Clinical Research Fellowship £206,000 over 3 years
Recent Publications

The Evolution of Therapies Targeting Bruton Tyrosine Kinase for the Treatment of Chronic Lymphocytic Leukaemia: Future Perspectives Eyre TA, Riches JC Cancers (2023) 15(7)

Opinion: What defines high-risk CLL in the post-chemoimmunotherapy era? Edelmann J, Malcikova J, Riches JC Frontiers in Oncology (2023) 13(7)

Spotlight on New Therapeutic Opportunities for MYC-Driven Cancers D’avola A, Kluckova K, Finch AJ et al. OncoTargets and Therapy (2023) 16(7) 371-383

Advances in Understanding of Metabolism of B-Cell Lymphoma: Implications for Therapy Kluckova K, D’Avola A, Riches JC Cancers (2022) 14(7)

The Use of Breath Analysis in the Management of Lung Cancer: Is It Ready for Primetime? Keogh RJ, Riches JC Current Oncology (2022) 29(7) 7355-7378

2022 update on the clinical outcome of coronavirus disease 2019 in haemato-oncology patients Bradwell S, Hone L, Thorneycroft K et al. Leukemia Research (2022) 119(7)

B-cell Receptor Signaling Induced Metabolic Alterations in Chronic Lymphocytic Leukemia Can Be Partially Bypassed by TP53 Abnormalities Kluckova K, Clear AJ, D'Avola A et al. HemaSphere (2022) 6(7) E722

Guideline for the treatment of chronic lymphocytic leukaemia Walewska R, Parry-Jones N, Eyre TA et al. British Journal of Haematology (2022) 197(7) 544-557

PHGDH is required for germinal center formation and is a therapeutic target in MYC-driven lymphoma D’Avola A, Legrave N, Tajan M et al. Journal of Clinical Investigation (2022) 132(7)

Richter transformation of chronic lymphocytic leukaemia: a British Society for Haematology Good Practice Paper Eyre TA, Riches JC, Patten PEM et al. British Journal of Haematology (2022) 196(7) 864-870

For additional publications, please click here
Team

Postdoctoral Researchers

PhD Students

  • Dr Oscar Atkins (based at the Francis Crick Institute)

Alumni

  • Dr Annalisa D’Avola

  • Dr Nicola Joseph

  • Dr Lotte Stiekema

Biography

I undertook my undergraduate degree in medical sciences at the University of Cambridge before qualifying from Oxford University Medical School in 2003. I subsequently trained in haematology on the Imperial College training rotation based at Hammersmith hospital.

I developed my research interest during my CRUK Clinical Research Fellowship with Professor Gribben at Barts Cancer Institute where I studied the defects underlying impaired T-cell immunity in chronic lymphocytic leukaemia (CLL) focusing on the impact of lenalidomide, being awarded a PhD in 2013. I stayed in this laboratory for a period of post-doctoral work investigating the expression and function of integrins on CLL cells. I was awarded the Hamblin prize by the UK CLL forum in 2015 for my work documenting the particular differences associated with the presence of trisomy 12.

In 2016, I joined the Centre for Haemato-Oncology in the Barts Cancer Institute as a Clinical Senior Lecturer funded initially as an Intermediate Clinical Fellow by the Wellcome Trust. From 2016-2021 I worked on secondment at the Francis Crick Institute to investigate the metabolism of normal and malignant B cells in collaboration with Professors Karen Vousden and Dinis Calado.

2018: Fellowship of the Higher Education Academy (FHEA)

2015: Fellowship of the Royal College of Pathologists (FRCPath)

2013: PhD, Queen Mary University of London

2006: Membership of the Royal College of Physicians (MRCP)

2003: MB BCh, University of Oxford

2000: MA Medical Sciences, University of Cambridge