Profile
Biography
Paul Kaye is Professor of Immunology and Director of the Centre for Immunology and Infection (CII). He obtained his undergraduate degree in Zoology from Imperial College in 1981 and his PhD in Immunology from University College London in 1984. At UCL, he studied the heterogeneity of antigen presenting cells, working in Prof. Sir Marc Feldmann's laboratory at the ICRF Tumor Immunology Unit. Paul then moved to the London School of Hygiene and Tropical Medicine for a post-doc with Jenefer Blackwell, examining how the macrophage natural resistance gene Nramp1 affected antigen presentation. Paul was appointed Lecturer in Immunology in 1988 and became Professor of Cellular Immunology and Head of the Immunology Unit in 1998. He joined the University of York and the Hull York Medical School (HYMS) in 2004, establishing the Immunology and Infection Unit, the predecessor to the CII. Paul is also Deputy Dean (Research) for HYMS.
Career
- Imperial College
BSc in Zoology (1981)
- University College, London
PhD in Immunology (1984)
- London School of Hygiene and Tropical Medicine
Research Fellow, Lecturer, Senior Lecturer (1985 - 1995)
Head, Biological Services Unit (1991 - 1993)
Head, Immunology and Cell Biology Unit (1993 - 1995)
Reader in Immunology (1995 - 1998)
Head of the Immunology Unit (1997 - 2000)
Professor of Cellular Immunology (1998 - 2004)
Co-Director, Wolfson Centre for Cell Biology (1999 - 2004)
- Centre for Immunology and Infection
Professor of Immunology (2004 - )
Director (2004 - )
Departmental roles
- Director of the Centre for Immunology and Infection
- Deputy Dean (Research), HYMS
- Chair, Department of Biology Ethics Committee
Research
Overview
- Antigen presentation
- Immunopathology
- Leishmaniasis
- Dendritic cells
- Imaging
- Inflammation
- Macrophages
Paul's laboratory continues to focus on antigen presenting cells (APC), with a particular emphasis on the temporal and tissue-specific changes that occur in the APC compartment during the progression of inflammatory and infectious disease. Although experimental models of visceral leishmaniasis provide the major context in which these studies are performed, the laboratory has more recently introduced other infectious and non-infectious models to complement and extend these studies. Ongoing projects span fundamental research into macrophage and dendritic cell development, heterogeneity and function, and translational projects aimed at taking this knowledge forward for the development of new therapeutic tools and vaccines.
Technologies
2-photon intravital microscopy, immuno-histochemistry, functional genomics; computational immunology; gene targeted models of chronic infection / inflammation
Current projects
- Immunopathology, stromal cell function and immune regulation
In experimental models of visceral leishmaniasis, parasites can be found in multiple systemic organs, but control of parasite burden is tissue-specific. In the liver, granulomatous inflammation provides the means for parasite containment and eventual elimination. In contrast, the spleen undergoes tremendous enlargement, accompanied by extensive remodeling of tissue architecture and parasite persistence. These diverse settings provide unique opportunities to examine how microenvironment affects APC differentiation and function. Current projects include: the function and fate of marginal zone macrophages; the role of DC cytokine production in regulatory T cell differentiation; the role of angiogenesis in splenic tissue remodeling; immunotherapeutic applications of costimulatory molecule blockade.
- Macrophage and dendritic cell heterogeneity
Macrophages and dendritic cells show considerable tissue specific diversity in form and function. Active research projects in this area include: gene expression profiling of tissue macrophage subsets and their response to Leishmania infection; the role of Irf-7 in regulating macrophage function; immunoregaultory functions of Kupffer cells; computational modeling of hepatic inflammation.
- Reproductive tract immunology
With Charles Lacey, we are conducting comparative studies of the human and rodent female genital tract, as a means to inform the development of new microbicides and vaccines for sexually transmitted infections (inc. HIV) and to develop new in vitro organotypic assays for candidate drug screening. Current laboratory projects include a study of the role of FcRn in IgG transport and research on the heterogeneity and regulation of vaginal DC. These studies complement ongoing clinical trials of new microbicides and vaccines with the HIV EUROPRISE Network.
- Development of novel immune potentiators
In collaboration with Dianna Bowles and Jack Lim in the Centre for Novel Agricultural Products, we are using a novel platform of recombinant glycosyltransferases derived from Arabidopsis thaliana to regiospecifically modify a variety of small molecule scaffolds with known activity on dendritic cells.
Using this technology, in conjunction with high content screening approaches, we aim to develop novel adjuvants and immunotherapeutics with fine-tuned activity profiles.
- Therapeutic vaccines for visceral leishmaniasis
Our studies in experimental visceral leishmaniasis indicate that (re-)activation of CD8+ T cells responses may provide synergy with chemotherapy in the treatment of human disease. With funding from a Wellcome Trust Translation Award, we are progressing these studies through their final pre-clinical stages, with the aim of conducting a first-in-man trial in UK volunteers in late 2012.
Research group(s)
Grants
- Wellcome Trust Translational Award
Co-PI, with Walden and Lacey, 'Therapeutic CD8+ T cell-biased vaccines for human visceral leishmaniasis' 01/10/08 - 30/06/13
- Wolfson Foundation
PI, with Lacey and Smith, 'Development of the Wolfson Laboratories in the Centre for Immunology and Infection'
- MRC Programme Grant
PI, "Immunology and Immunopathology of Visceral Leishmaniasis" 01/01/11 - 31/12/15
- Wellcome - Wolfson Foundation Infrastructure Award
Centre for Hyperpolarisation in MRI, co-application with Duckett & Green (PIs)
- EU FP7 Marie Curie Initial Training Network, PI, 'Stromal Cell - Immune Cell Interactions in Health and Disease', 01/01/12-31/12/15, STROMA
Available PhD research projects
New Early Stage Researcher position within the STROMA ITN (2012 - 2013)
The research project will focus on the 'Regulation of dendritic cell development and function by bone marrow stromal cells during chronic inflammation' and it is based at the Centre for Immunology and Infection at the University of York.
Bone marrow stromal cells play an important role in the regulation of hematopoiesis but how their function is affected by systemic inflammation is poorly understood. We have previously shown that during experimental leishmaniasis, there is an increase in the bone marrow output of myeloid precursor cells, and that stromal cells have the potential to direct the differentiation of these precursors into DCs with regulatory function. However, the identity of the stromal cell subpopulations affected by inflammation and the molecular changes they undergo are unknown. This project will combine a variety of state-of-the-art approaches in cellular immunology (including intra-vital imaging, flow sorting and transcriptomics) with models that allow stromal cell-specific gene targeting, to generate important new insights into how inflammation affects the bone marrow niche that supports the development of DCs and other myeloid cells.
Please visit www.stromal.org for further information and to submit your on-line application.
Please email paul.kaye@york.ac.uk for further enquiries.
Deadline: 14 September 2012
For application requirements, process, and guidelines please see the postgraduate study pages of the Department of Biology website (http://www.york.ac.uk/biology/postgraduate/). New available studentships are announced on these web pages, the Departmental site and on FindAPhD.