Professor Paul Kaye

PhD, FRCPath, FMedSci

Professor of Immunology

Biography

Paul Kaye is Professor of Immunology at the University of York. He trained in zoology (BSc) and immunology (PhD) and has worked for over 30 years on the immunology and immunopathology of the neglected tropical disease leishmaniasis. He is internationally recognised for his research on macrophages and dendritic cells, contributing to a fundamental understanding of their biology in health and disease, and for his work on lymphoid tissue remodelling and granulomatous inflammation during chronic infection. Paul is a Wellcome Trust Senior Investigator and an elected Fellow of the UK Academy of Medical Sciences. He was awarded FRCPath by publication in 2004 and has published ~150 research articles and reviews, with numerous in leading international journals (e.g. Nature Medicine, Immunity, J. Clin. Invest., PNAS). Paul’s research tackles leishmaniasis from a holistic viewpoint, rooted in the immunology of the host-parasite interaction, but employing tools and approaches taken from many disciplines, including mathematics, ecology, vector biology and neuroscience. He has extensive links with leishmaniasis-endemic countries and is currently leading a Phase II therapeutic vaccine trial in Sudan and developing a digital pathology platform to facilitate a greater understanding of disease pathogenesis through data sharing and collaboration across geographic borders.

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 - 2015)
Research

Overview

  • Antigen presentation
  • Dendritic cells
  • Imaging
  • Immunopathology
  • Inflammation
  • Leishmaniasis
  • Macrophages

Paul's laboratory continues to focus on the immunopathology of leishmaniasis, with emphasis both on exploring opportunities for developing novel host-directed therapies and also for gaining new insight into myeloid cell function. Ongoing projects span fundamental research into macrophage and dendritic cell development, heterogeneity and function, studies on the immunological determinants of transmission to sand flies, research on human immunopathology, and clinical trials of a new vaccine for leishmaniasis.  His research group has active collaborations in Brazil, India, Sri Lanka and across East Africa.

Technologies

2-photon intravital microscopy, immuno-histochemistry, functional genomics; computational immunology; gene targeted models of chronic infection / inflammation; sand fly transmission; digital pathology; early phase clinical trials.

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 Kupffer cells; lipid metabolism in DCs; regulation of microglial activation during systemic infection; monocyte subsets and their role in visceral leishmaniasis. 
  • Host determinants of infectiousness in visceral leishmaniasis 
    We have developed a new model of outward transmission of Leishmania donovani that is allowing us for the first time to determine the sites where sand flies acquire parasites during a blood meal.  Our data indicate that parasites are heterogeneously distributed within the skin, and mathematical models coupled with sand fly transmission experiments have been used to demonstrate the importance of parasite load and distribution to transmission.  
  • Immuno-pharmacology
    To better understand drug-immune interactions, we are developing computational multiscale models of immunity coupled to PK modelling.  Current research focuses on using mass spectroscopy and MS-Imaging to identify drug distribution at the sub tissue level. 
  • Towards a Molecular stratification of leishmaniasis
    To add value from clinical biopsies and encourage data sharing across leishmaniasis endemic regions, we are developing a digital pathology platform (LeishPathNet.org), and researching new methods for multidimensional and muliparameter molecular characterisation of tissue biopsies (Nanostring; RNAscope). 
  • Therapeutic vaccines for visceral leishmaniasis 
    With funding from a Wellcome Trust Translation Award, we are currently conducting a Phase IIa safety trial in Sudan of a novel third generation adenoviral vaccine for use a s a therapeutic in patients with persistent post kala-azar dermal leishmanaisis.  If this trial indicates that the vaccine is safe, we will proceed to a Phase IIb randomized control trial to assess whether it can provide clinical benefit in this difficult to treat patient group.

Grants as PI

  • MRC Global Challenges Research Fund Foundation Award: “Towards a global research network for the molecular pathological stratification of Leishmaniasis”; 01/03/17 - 28/02/19

  • Wellcome Trust Translation Award: “A Phase lla/llb clinical trial to evaluate the therapeutic efficacy of ChAd63-KH vaccine in patients with persistent PKDL”; 01/05/16 – 31/10/2020

  • Wellcome Trust Senior Investigator Award: “Determinants of host infectiousness in visceral leishmaniasis”; 01/01/16 - 31/12/20.

  • NC3Rs / SBRI CRACKIT Challenge Award: “A multiscale model to minimize animal usage in leishmaniasis drug development”; 01/01/15 -31/12/1
Teaching

Paul teaches immunology, infection and pathology in Phase 1 Medicine.

Publications

Visit Professor Paul Kaye's profile on the York Research Database to see a full list of publications, browse activities and projects, explore connections, collaborations, related work and more.