Research in the department falls into three main areas with major relevance for human disease. The Haematopoiesis and Leukaemia Group are based in the Cambridge Institute for Medical Research (Professor Green, Professor Göttgens, Dr Huntly, Dr Ottersbach) and the MRC Laboratory of Molecular Biology (Professor Warren). The Structural Medicine and Thrombosis Group (Professor Read, Professor Huntington) are based in the CIMR, and the Transfusion Medicine Group (Professor Allain, Dr Lee, Professor Ouwehand, Dr Ghevaert) are based in the NHS Blood and Transplant Building.
Recent research initiatives include the establishment of a $6.0M Specialist Centre for Research, funded by the US Leukemia and Lymphoma Society, the only one in Europe. The department has also played a leading role in establishing a £5.8M European Bloodomics programme.
Haematopoiesis and leukaemia. Haematopoiesis represent the best characterised adult stem cell system and continues to provide important paradigms for understanding other stem cells as well as cancer biology. The focus of this group continues to be the transcriptional regulation of blood stem cells, and the mechanisms whereby such stem cells are subverted to form leukaemias. Current research programmes include:
1) Myeloproliferative neoplasms, JAK/STAT signalling and stem cell subversion (Professor Green).
2) Transcriptional networks regulating blood stem cells (Professor Göttgens).
3) The pathogenesis of bone marrow failure syndromes and leukaemia (Professor Warren).
4) The biology of leukaemia stem cells (Dr Huntly).
5) The developmental origin of haematopoietic stem cells (Dr Ottersbach).
Structural medicine and thrombosis. Structural biology gives an unparalleled insight into the molecular details of biological mechanisms, an insight that has the potential to lead to rationally-designed therapies. This is illustrated by some recent studies. Professor Huntington is studying the details of the delicate control of coagulation by members of the serpin family of serine protease inhibitors; over the past year, new insights have been gained into the control by serpins of factor IXa and thrombin. Dr Zhou is studying members of the serpin family adapted for non-inhibitory roles, with a series of structures of angiotensinogen and its complex with renin revealing a new mechanism by which oxidative stress modulates the control of blood pressure. The determination of such structures is heavily driven by computer methods, an area to which Professor Read’s group is making significant contributions.
Transfusion medicine. The focus of Transfusion Medicine research is in blood borne viruses, diagnostics and transfusion in resource poor areas, biology and genomics of megakaryocytes and platelets. Particular highlights include:
1) Global studies of the molecular epidemiology of Hepatitis B virus in collaboration with major blood centres around the world. The genomes of HBsAg- and HBsAg+ strains have been sequenced and analysed. (Professor J-P Allain).
2) A Genome-Wide Association Study meta-analysis which identified 15 genetic loci that regulate the volume and count of platelets and the discovery of novel genetic loci that regulate platelet function (Professor Willem H Ouwehand).
3) A rapid low cost diagnostic test for Chlamydia trachomatis has been developed and is now widely available. A test for HBsAg is being submitted for licensing (Dr H Lee).