MB ChB PhD MRCP(UK) FRCPath
Professor of Haematology
- Attending Consultant Physician
Haematopoietic Transplantation and Immunotherapy
I obtained my medical degree from the University of Birmingham before training in internal medicine and haematology in Cambridge and Oxford. I joined Professor Ian Hickson’s DNA repair laboratory as a MRC Clinical Training Fellow at the Weatherall Institute of Molecular Medicine and completed my PhD in 1998. In 2000, I was awarded a LRF Bennett Senior Fellowship in Experimental Haematology. This award allowed me to join Professor Megan Sykes’ laboratory at the Transplant Biology Research Center, Harvard Medical School; here, my post-doctoral research focussed upon the mechanisms that regulate immune tolerance following reduced intensity transplantation. I moved to UCL in 2005, where I developed a translational research program focussing on T cell immunotherapy with a track record of delivering proof-of-concept trials in human patients. Following my appointment as Professor in 2013, I led the merger of the transplant services of the Royal Free and University College London Hospital to create one of the largest haematopoietic transplantation and immunotherapy programs in Europe. In 2020, I was recruited as Professor of Haematology at the University of Oxford, where I am now leading efforts to create infrastructure required for delivery of first-in-human trials in advanced cell and gene therapy.
My research is centred on exploring mechanisms that dictate the success or failure of T cell immunotherapies for cancer. We use pre-clinical models and patient samples to inform the design of new strategies that can be translated into early phase clinical trials. Our work has identified a strong pre-disposition to CD8+ T cell exhaustion in several model systems, as well as in non-responding patients. Our group is currently developing targeted approaches to overcome loss of anti-leukaemia T cell functions, for example through the provision of CD4+ T cell help, manipulation of metabolic pathways or gene engineering to redirect T cells to the bone marrow. We are also examining how enhanced immunity can lead to immune-related adverse events, for example graft-versus-host disease after haematopoietic transplantation. In particular, we are interested in understanding how T cell pathogenicity and resistance to immune suppressive drugs is regulated by cellular and molecular interactions within individual tissues.
As a clinical investigator, I have led several innovations to improve the therapeutic index of transplantation including optimization of methods for T cell depletion, graft engineering and addback of selected T cell populations, and treatment of GVHD.
- Dertschnig S., Evans P., Santos e Sousa P., Manzo T., Ferrer I.R., Stauss H.J., Clare Bennett C. and Chakraverty R. 2020. Graft-versus-host disease reduces lymph node expression of tissue-restricted antigens and promotes autoimmunity. JCI 130:1896-1911
- Ferrer IR, West HC, Henderson S, Ushakov DS, Santos E Sousa P, Strid J, Chakraverty R, Yates AJ, Bennett CL. 2019. A wave of monocytes is recruited to replenish the long-term Langerhans network after immune injury. Science Immunology 2019 4(38); pii: eaax8704
- Khan AB, Carpenter B, Sousa PSE, Pospori C, Khorshed R, Griffin J, Velica P, Zech M, Ghorashian S, Forrest C, Thomas S., Gonzalez Anton S., Ahmadi M., Holler A’, Flutter B., Ramirez-Ortiz Z., Means T.K., Bennett C.L., Stauss H., Morris E., Lo Celso C., Chakraverty R. 2018. Redirection to the bone marrow improves T cell persistence and antitumor functions. JCI 128:2010-2024
- Santos ESP, Cire S., Conlan T., Jardine L., Tkacz C., Ferrer I.R., Lomas C., Ward S., West H., Dertschnig S., Blobner S., Means T.K., Henderson S., Kaplan D.H., Collin M., Plagnol V., Bennett C.L. and Chakraverty R. 2018. Peripheral tissues reprogram CD8+ T cells for pathogenicity during graft-versus-host disease. JCI Insight 3(5) pii 90711
Idelalisib treatment prior to allogeneic stem cell transplantation for patients with chronic lymphocytic leukemia: a report from the EBMT chronic malignancies working party
Schetelig J. et al, (2020), Bone Marrow Transplantation
Predictors of recovery following allogeneic CD34+-selected cell infusion without conditioning to correct poor graft function.
Cuadrado MM. et al, (2019), Haematologica