Research Focus
My major research interest is understanding the metabolism of chronic lymphocytic leukaemia and lymphoma with the aim that this will underpin the development of the next generation of anti-metabolic drugs for these diseases.
Key Publications
Mechanisms of PD-L1/PD-1 mediated CD8 T-cell defects in the context of aging-related immune defects in the Eµ-TCL1 CLL mouse model. Blood (2015) 9;126(2):212-21. PMID: 25979947
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
Activated Pancreatic Stellate Cells Sequester CD8+ T-Cells to Reduce Their Infiltration of the Juxtatumoral Compartment of Pancreatic Ductal Adenocarcinoma. Gastroenterology (2013) 145(5): 1121-32 PMID: 23891972
Major Funding
- 2019 - Kay Kendall Leukaemia Fund: Investigating the molecular mechanisms underlying increased glycolysis in high grade transformation of chronic lymphocytic leukaemia, £217,498
- 2016- Wellcome Trust Intermediate Clinical Fellowship, Understanding the impact of p53 abnormalities on cellular metabolism in chronic lymphocytic leukaemia, £863,503
Other Activities
- 2014-2015: Intercollegiate Committee on Haematology
- 2014-2015: Trainees Advisory Committee Representative
- 2013-2015: UK CLL Forum Executive Committee
Research
My research focus is investigating the interplay between BCR-signalling and metabolism in chronic lymphocytic leukaemia using a variety of proteomic and metabolomic techniques. We are particularly interested in the impact of deletions/mutations of p53 on the metabolism of CLL cells and how this relates to Richter syndrome and other high grade lymphomas.
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. I have a particular interest in the role of targeted therapies, immunotherapy and bone marrow transplantation in the treatment of these diseases.
Other Activities
- 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
- 2016- Wellcome Trust Intermediate Clinical Fellowship, Understanding the impact of p53 abnormalities on cellular metabolism in chronic lymphocytic leukaemia, £863,503
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
Biography
I qualified from Oxford University Medical School in 2003 and 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 interaction between signalling and metabolism in CLL and lymphoma cells in collaboration with Professor Karen Vousden.