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

• 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

• 2019 - Kay Kendall Leukaemia Fund: Investigating the molecular mechanisms underlying increased glycolysis in high grade transformation of chronic lymphocytic leukaemia, £217,498
• 2019 - Greg Wolf Leukaemia Fund: Investigating the impact of TP53 abnormalities on glycolysis in Richter syndrome, £22,000
• 2016- Wellcome Trust Intermediate Clinical Fellowship, Understanding the impact of p53 abnormalities on cellular metabolism in chronic lymphocytic leukaemia, £863,503
• 2009 - Cancer Research UK Clinical Research Fellowship £206,000 over 3 years

Recent Publications

Mechanistic and clinical aspects of lenalidomide treatment for chronic lymphocytic leukemia. Riches JC, Gribben JG Current Cancer Drug Targets (2016) 16(1)
http://www.ncbi.nlm.nih.gov/pubmed/27055579

Mechanisms of PD-L1/PD-1-mediated CD8 T-cell dysfunction in the context of aging-related immune defects in the Eµ-TCL1 CLL mouse model. McClanahan F, Riches JC, Miller S et al. Blood (2015) 126(2) 212-221
https://www.ncbi.nlm.nih.gov/pubmed/25979947

PD-1/PD-L1 mediated T-cell dysfunction in CLL is not absolute and can be at least partially reversed in vivo by the immune-modulatory drug lenalidomide McClanahan F, Riches JC, Miller S et al. ONCOLOGY RESEARCH AND TREATMENT (2014) 37(11) 236-236
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000343816900576&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

Immunomodulation and immune reconstitution in chronic lymphocytic leukemia. Riches JC, Gribben JG Semin Hematol (2014) 51(2) 228-234
https://www.ncbi.nlm.nih.gov/pubmed/25048786

Trisomy 12 chronic lymphocytic leukemia cells exhibit upregulation of integrin signaling that is modulated by NOTCH1 mutations Riches JC, O'Donovan CJ, Kingdon SJ et al. BLOOD (2014) 123(11) 4101-4110
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000342618100014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

Trisomy 12 chronic lymphocytic leukemia cells exhibit upregulation of integrin signaling that is modulated by NOTCH1 mutations. Riches JC, O'Donovan CJ, Kingdon SJ et al. Blood (2014) 123(2) 4101-4110
https://www.ncbi.nlm.nih.gov/pubmed/24829201

Hanging tough: CMV-specific CD8+ T cells in CLL. Riches JC, Gribben JG Blood (2014) 123(2) 608-609
https://www.ncbi.nlm.nih.gov/pubmed/24482498

Advances in chimeric antigen receptor immunotherapy for chronic lymphocytic leukemia. Riches JC, Gribben JG Discov Med (2013) 16(2) 295-302
https://www.ncbi.nlm.nih.gov/pubmed/24333409

Intraclonal Complexity Of CLL Fractions In Cell Proliferation Rates, Gene Expression Signatures, and Responses To Autologous T-Cell Help In Peripheral blood and Secondary Lymphoid Tissues Chen S-S, Herndon TM, Emson C et al. BLOOD (2013) 122(11)
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000331385000142&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

Activated pancreatic stellate cells sequester CD8+ T cells to reduce their infiltration of the juxtatumoral compartment of pancreatic ductal adenocarcinoma. Ene-Obong A, Clear AJ, Watt J et al. Gastroenterology (2013) 145(2) 1121-1132
https://www.ncbi.nlm.nih.gov/pubmed/23891972

Team

Postdoctoral Researchers
Dr Katarina, Kluckova, Dr Annalisa D’Avola (based at the Francis Crick Institute)

PhD Students
Nicola Joseph

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. I have been working at the Francis Crick Institute to investigate the metabolism of normal and malignant B cells in collaboration with Professor Karen Vousden and Dinis Calado.

2018: Fellowship of the Higher Education Academy (FHEA)

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

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

2003: MB BCh, University of Oxford

2000: MA Medical Sciences, University of Cambridge