Research

Our research group, based in the Department of Surgery in Cambridge, is focused on interdisciplinary and translational research that aims to increase access to transplantation and to improve long-term transplant outcomes. We are particularly interested in the human major histocompatibility complex proteins (called Human Leukocyte Antigens or HLA) and their role in transplant allo-immunity and graft injury. Much of our efforts in this area are focused on studying the genetic and structural characteristics of HLA proteins and the functional properties of HLA-specific antibodies to assess transplant immunological risk and to improve donor-recipient tissue matching. We are also interested in big-data analysis for phenotyping and forecasting in transplantation and in applying technological innovations, such as machine perfusion, to assess the quality of donor organs and improve their function after transplantation.

We work collaboratively with colleagues in academia and industry and utilise a variety of techniques to address our research questions, including computational structural and physicochemical protein modelling, cryo-Electron microscopy, protein chemistry, molecular biology methods, microfluidics, transcriptomics and proteomics analyses. Research in the group has been licensed to industry and led to the development of widely used HLA immunogenicity analysis software.

Current Research

Human Leukocyte Antigen immunogenicity, humoral alloimmunity and immunological risk assessment in transplantation

  • Structural analysis of alloantibody-HLA interactions and of HLA B-cell epitopes - We are interested in understanding the structure of immunogenic HLA B-cell epitopes that drive humoral alloimmune responses in transplant recipients and study the molecular basis of alloantibody-HLA interactions. Read more
  • Biophysical assessment of HLA-alloantibody interactions and profiling of alloantibody function - We are interested in understanding how alloantibodies mediate their action through their Fab and Fc regions and in developing novel assays to profile their functional properties. Read more
  • HLA molecular mismatch algorithms and HLA-related immunological risk - Our lab has pioneered the development of computational algorithms (Cambridge HLA Immunogenicity algorithm and HLA Electrostatic Mismatch Score 3-Dimensional) to predict the immunogenic potential of donor HLA and provided evidence that this approach can be used as a prognostic biomarker of primary alloimmunity. Read more
  • Non-invasive assessment of the conditional state of transplant organs - We capitalise on biological samples from transplant patients and from experimental and clinical ex vivo normothermic machine perfusion studies to identify biomarkers of organ quality and to investigate mechanisms of ischaemia-reperfusion injury (IRI) and its effect on graft function.Read more
     
  • Donor organ assessment and reconditioning using ex vivo machine perfusion - Our department has pioneered the development and clinical translation of normothermic machine perfusion as a platform for assessment and reconditioning of donor organs (liver and kidney).Read more