The Division of Transplantation, directed by Professor Andrew Bradley, continues to be at the international forefront of clinical developments in organ transplantation. Our world-renowned clinical programmes in abdominal organ transplantation based at Addenbrooke’s Hospital, and thoracic organ transplantation based at Papworth Hospital, are each underpinned by well-established multidisciplinary research programmes. Research ranges from basic molecular and cellular immunology to translational research and evaluation of new technologies. The Division includes the Transplantation and Regenerative Medicine Theme of the NIHR Cambridge Biomedical Research Centre. There are strong programmes of basic research into the molecular basis of allograft rejection, with a particular focus on the role of B cells and alloantibody, acute and chronic rejection, interactions between endothelial and immune cells in allograft vasculopathy, and molecular mechanisms underlying the induction and maintenance of immunological tolerance. Our clinical interest in histocompatibility and immunogenetics is supported by collaborative research with Dr Craig Taylor, investigating KIR compatibility in transplantation and analysis of physicochemical properties determining the immunogenicity of HLA molecules. The division is undertaking a number of investigator-led single and multi-centre clinical research programmes aimed at evaluating novel immunosuppressive agents, extending donor organ use and minimising organ injury prior to transplantation. Senior investigators in the department are also working closely with scientists and statisticians at NHS Blood and Transplant to maximise the outcome of organ transplantation in the UK.
Stem Cell Medicine
Groups led by Professor Roger Pedersen and Professor Ludovic Vallier are conducting research into the early stages of embryonic stem cell differentiation and the genetic mechanisms responsible for these processes. Both mouse and human embryonic stem (hES) cells are studied, and small interfering (si)RNAs are being used to modify gene function and examine the role of specific genes, with the aim of ultimately controlling differentiation into specialised cell types for potential therapeutic use. Research is also undertaken into the mechanisms responsible for the maintenance of pluripotency in heS cells and the formation of mesodermal and endodermal cell lineages, as well as the epigenetic stability of pluripotent stem cell lines. Both groups interact extensively with other leading investigators within and outside the University; both are key contributors to the Cambridge Stem Cell Initiative, which aims at biomedical translation of stem cell and regenerative medicine research. Both Professor Pedersen and Professor Vallier are founding members of the School of Clinical Medicine’s Anne McLaren Laboratory for Regenerative Medicine (LRM). The LRM has played a key role in the Cambridge Stem Cell Initiative by serving as the Clinical School host for the MRC Centre’s Centre for Stem Cell Biology and Regenerative Medicine, which together with the Wellcome Trust Centre for Stem Cell Research on Tennis Court Road constitute the hubs of the Cambridge Stem Cell Initiative. In 2009, Professor Vallier established the human induced pluripotent stem cell Core Resource, with support from the National Institute for Health Research Cambridge University Hospitals Trust Biomedical Research Centre. During the past two years, the hiPSC Core Facility has derived more than 400 hiPSC lines from 60 patients suffering from neurodegenerative diseases, cardiovascular syndromes, metabolic and blood disorders. In parallel, the hiPSC Core Facility has become a major training centre by accommodating more than 20 visiting scientists and by supporting the development of similar platforms in several European countries.
The Division of Trauma and Orthopaedics, directed by Professor Andrew McCaskie, has a novel programme of fundamental and translational research in bone and joint repair using in vitro and in vivo approaches. The basic science programme is designed to elucidate the developmental cascade of the osteoblast and chondrocyte lineages, both from known precursors and novel sources, and to understand their interaction with normal and newly developed matrices. Understanding how local niches impinge on the developmental cascade is a new theme. In addition to investigations on the developmental cascade there is an on-going programme investigating the damage/repair response of the osteochrondral unit. In collaboration with the Departments of Materials Science and Engineering, we are evaluating the interactions of human cells and in particular mesenchymal stem cells with collagen-based materials for the regeneration of cartilage, meniscus and tendon. Within the Department of Chemistry we are using nuclear magnetic resonance spectroscopy to investigate chemical signatures within bone matrix and between the matrix and mineral phases of bone. Translational research has resulted in the CE marking and first in man trials of an osteochondrial repair product following development work carried out in the Unit. The clinical use of bone substitute materials in impaction grafting has been supported by research on the mechanical properties of mixtures of bioactive ceramic and bone.
The uro-oncology division, previously directed by Professor David Neal, is closely associated with the Departments of Oncology and Surgery. Cambridge has the largest robotic prostatectomy programme within the NHS and this, together with other clinical trials, has allowed the development of a well-annotated bio-repository. The division runs a major NIHR funded trial (ProtecT) to determine the best treatment for men with early prostate cancer and is the largest ever surgical trial in prostate cancer. Collaborative genetic research continues with Strangeways and the ICR in London. There is a large translational research programme involving Mr Vincent Gnanapragasam and experimental medicine studies including imaging led from the Cambridge Research Institute. Following studies of SNPs in prostate cancer, novel biomarkers have been developed. The majority of the work in the CRI is focused on androgen receptor signalling where we have discovered novel binding sites and functionally important therapeutic targets.