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The 5-year programme award will support research on the DNA repair mechanisms that protect cancer cells from therapy, informing the development of future treatments.
Development of the hematopoietic/ immune system in the embryo
Modelling stem cell fate and alterations due to mutations
Our group is interested in developing novel immunotherapeutic approaches for leukaemia. Clinical approaches currently used include allogeneic haematopoietic stem cell transplantation, chimeric antigen receptor T cell therapy and immune checkpoint inhibitors. While each of these approaches can be successful, they also fail in many patients as a result of tumour adaptations or diminished function of immune cells. Enhanced immunity can also lead to immune-related adverse events due to on- or off-target effects. We are exploring the mechanisms that underpin these failures and using this information to devise new strategies that can be translated into early phase clinical trials.
The Porcher lab investigates how Haematopoietic Stem Cells (HSCs, the cells with self-renewal and multilineage potentialities that give rise to the entire blood system) are produced during embryonic development. To do this, we study the developmental pathway of the blood lineage from mesoderm through to production of HSCs (see Figure) at mechanistic and functional levels. In addition to increasing our understanding of this fundamental biological process, better knowledge of how the first HSCs are generated during embryogenesis is critical to inform experiments aiming at producing HSCs in vitro for regenerative medicine purposes and to help explain how these processes, when corrupted, can lead to haematological malignancies (leukaemia) that manifest in early life.
Identification of key determinants affecting the quality of human cancer specific cytotoxic T cells
Development and Maturation of B cell Mediated Antibody Responses
De Novo Mutations and Human Disease
Using state-of-the-art laboratory and computational approaches to understand how mammalian genes are switched on and off during development and differentiation and how this goes awry in human genetic diseases.
Single Cell Genomics
Nerlov Group - Single Cell Biology of Hematopoietic Stem- and Progenitor Cells in Blood Cancer and Ageing
The focus of the Nerlov laboratory is combining single cell biology (single cell RNAseq, ATACseq and functional analysis) with advanced mouse genetics to study hematopoietic stem– and progenitor cells in normal development and during ageing.
My lab is interested in understanding how the genome functions and leveraging this to develop genome editing strategies to treat human disease.
Our focus has been on the cell biology of the T-cell surface. We developed general methods for crystallizing glycoproteins and determined the structures of key T-cell surface proteins including the first adhesion protein (CD2) and its ligand CD58, the costimulatory receptor CD28 and its ligand CD80, and the large tyrosine phosphatase CD45. We also worked out how weak, specific recognition is achieved by these types of proteins and obtained the first insights into the overall composition of the T-cell surface. Most importantly we proposed, with PA van der Merwe, one of the most complete and best-supported explanations for leukocyte receptor triggering, called the kinetic-segregation model (youtube.com/watch?v=HygSTSlycok). Please see http://davislab-oxford.org/ for more details of our lab’s activities.