Dr Jeff Davies

MA, MRCP, FRCPath, PhD
Centre: Haemato-Oncology
Clinical Senior Lecturer
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My clinical and research interests are allogeneic haematopoietic stem cell transplantation (HSCT); graft-versus-host disease (GvHD)/graft-versus-tumour (GvT) effects; and adoptive immunotherapy.

Research Details

In the lab I focus on the development of novel approaches to improve efficacy and reduce toxicity of allogeneic HSCT and adoptive immunotherapy as treatments for blood cancers and other diseases.

Current funded research projects include pharmacological modulation of immune responses after allogeneic HSCT, genetic manipulation of donor cells to externally control their phenotype and examination of the metabolic pathways that trigger gastro-intestinal GvHD.

I now combine my laboratory and translational research programme with clinical practice with the Cancer Centre at Barts Health, with specific emphasis on the lymphoma service and development of the allogeneic transplant/immunotherapy programmes.

Profile

I developed my research interest during my MRC Clinical Research Training Fellowship at the Royal Free Hospital, London, where I studied ways to selectively deplete alloreactive donor T cells to reduce GvHD but maintain immune reconstitution after allogeneic HSCT. I was awarded the George Santos Award by the American Society for Blood and Marrow Transplantation for the best clinical research by a young investigator for this research.

In 2006, I joined the Dana-Farber Cancer Institute/Harvard Medical School as a junior faculty member in Medical Oncology. I performed translational research with Profs Lee Nadler and Eva Guinan using costimulatory blockade to induce allospecific anergy in donor lymphocytes, to reduce GvHD but preserve immune reconstitution and GvL effects after allogeneic HSCT.

During that time I also gained experience in other adoptive immunotherapy approaches to cancer treatment, and I was the recipient of a Career Development Award from the Leukaemia and Lymphoma Society and a New Investigator Award from the American Society for Blood and Marrow Transplantation.

In 2010 I joined the Centre for Haemato-Oncology in the Barts Cancer Institute as a Clinical Senior Lecturer funded initially as a Clinician Scientist by the MRC.

Qualifications

  • MA (Oxon) Physiological Sciences First Class 1989
  • BM BCh (Hons) (Oxon) 1992
  • MRCP (UK) 1996
  • MRCPath 2002
  • PhD (University of London) 2005
  • FRCPath 2008

Funding

As principal investigator:

2015 - Bloodwise (formerly Leukaemia-Lymphoma Research) Project Grant ‘Defining the role of the Retinoic Acid Pathway in human gastro-intestinal GvHD
(Total £187,000)
2015 - Barts Charity Clinical Research Fellowship: "Integrated polyfunctional assessment of donor T-cell reconstitution after allogeneic haematopoietic stem cell transplantation to identify predictors of Graft-versus-Host Disease and Graft-versus-Tumour effects"
(Total £132,260)
2014 - MRC Clinical Research Fellowship: "Modulating human alloresponses with lenalidomide to improve the outcome of allogeneic haematopoietic stem cell transplantation"
(Total £230,000)
2014 - Barts Charity Small Project grant: "Creating human donor T cells with conditional FOXP3 expression to improve control of alloreactivity after allogeneic haematopoietic stem cell transplantation"
(£6090)
2011 - 2015 Medical Research Council, UK Clinician Scientist Award: "Generation of suppressive donor T cells to specifically control alloresponses after allogeneic stem cell transplantation"
£235,042 pa (Total £940,166)
2008 - 2010 American Society for Blood and Marrow Transplantation New Investigator Award: "The generation of alloantigen-specific CD4+CD25hi Regulatory T cells by repeat allostimulation of donor T cells alloanergized to recipient alloantigens"
£20,000 pa (Total £40,000)
2006 - 2009 Leukemia and Lymphoma Society, USA Career Development Award (Special Fellow in Clinical Research): "Optimizing Alloantigen-specific T cell Anergy in Hemopoietic Stem Cell Transplantation"
£40,000 pa (Total £120,000)
2008 - 2010 Burroughs Wellcome Fund, USA "Leukemia-specific alloantigen-anergic donor-derived T-cell therapy after umbilical cord blood transplantation-An example of disease management (therapeutic) aimed at a molecular target (CD19)"
PI: Dr Laurence Cooper (MD Anderson Cancer Center, Houston, Texas)
£15,000 pa (Total £30,000)
2008 - 2010 National Institutes of Health (NIH), USA R21 CA137645-01A1 Phase 1 Clinical Trial: "Ex Vivo Alloanergization to Improve Immunity after Haploidentical Transplant"
PI: Dr Eva Guinan (Dana-Farber Cancer, Boston, USA)
£175,000 pa (Total £300,000)

Key Publications

E Kotsiou, J Okosun, C Besley, S Iqbal, J Matthews, J Fitzgibbon, JG Gribben, JK Davies. TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses. Blood 2016. Jul 7;128(1):72-81. PMID: 27103745

Kotsiou E, Gribben JG, Davies JK. Allospecific Tregs expanded after anergization remain suppressive in inflammatory conditions but lack expression of gut-homing molecules. Molecular Therapy 2016. [Epub ahead of print] PMID: 27049761

CM Barbon*, JK Davies*, A Voskertchian, RH Kelner, L. Brennan, LM Nadler, EC Guinan. CD8+ Suppressor T Cells Contribute to Alloantigen-specific Immune Tolerance After Alloanergization. American Journal of Transplantation (2014) 14(2):305-18. PMID: 24410845
* Joint first authorship

Davies JK, Singh H, Huls H, Yuk D, Lee DA, Kebriaei P, Champlin R, Nadler LM, Guinan EC, and Cooper LJ. Combining CD19 Redirection and Alloanergization to Generate Tumor-Specific Human T Cells for Allogeneic Cell Therapy of B-Cell Malignancies. Cancer Research (2010) 70(10):3915-24. PMID: 20424114

Further Publications

For additional publications, please click here.


My clinical and research interests are allogeneic haematopoietic stem cell transplantation (HSCT); graft-versus-host disease (GvHD)/graft-versus-tumour (GvT) effects; and adoptive immunotherapy.

External Activities

  • British Society for Blood and Marrow Transplantation member
  • National Steering Committee Chair HLA-epitope matching and platelet transfusion study
  • London Cancer Pathway board for lymphoma 2015
  • Invited speaker at UK Haematology Forum 2012 and 2014

News

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Blood cancers Clinical Trials Immunology Leukaemia Lymphoma
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