Stem Cell Biology
Several of our team leaders have interests focussing on stem cell biology, both in health and in disease. Professor Myrtle Gordon’s current interests include the mechanisms controlling the kinetics of haemopoietic stem and progenitor cell self-renewal (including cytokines, chemokines, oncogenes, cell cycle proteins and extracellular matrix proteins). In particular her group is interested in the role of CD34, a cell surface protein expressed on primitive hemopoietic progenitor cells, in homotypic progenitor cell adhesion in the regulation of normal haemopoiesis. This results in polarisation of several molecules including sialomucins, CD34 and CD164. Work on normal progenitors is closely linked with the investigation of these characteristics in cells from patients with chronic myeloid leukemia (CML), a disease which forms a major interest of the department. A collaboration with Professor Nagy Habib (Department of Surgery) is investigating the potential of stem cells in regenerative medicine, particulary in the treatment of patients with liver insufficiency.
Dr Nicki Panoskaltsis leads a programme of research in leukaemogenesis, particularly focussed on the immune pathogenesis of acute myeloid leukaemia (AML) and the role of dendritic cells at disease presentation and in immune recovery following treatment. In studying leukaemia, she also conducts research in parallel on normal stem cells and haemopoiesis. Current projects include the study of haemopoietic stem cell “plasticity”, the expansion of cord blood stem cells in normal and bioreactor cultures and the modeling and development of a novel three-dimensional culture system that mimics the normal and leukaemic bone marrow microenvironment in collaboration with Dr Athanasios Mantalaris (Department of Chemical Engineering).
Both Professor Irene Roberts and Professor Francesco Dazzi have programmes involving exploitation of the properties of mesenchymal stem cells including their immunoregulatory capabilities (which may be valuable in alogeneic stem cell transplantation) and their capacity for multi-lineage differentiation. This part of Professor Robert’s work sits comfortably within a wider framework of the study of the ontogeny of haemopoiesis in the human fetus and the mechanism of haematological abnormalities in newborn babies. The lab has developed unique miniaturized assays for haemopoietic progenitors from early in the first trimester and has a particular interest in fetal megakaryocytopoiesis and fetal mesenchymal cells and the pathogenesis of the fetal megakaryoblastic leukaemia associated with Down syndrome (trisomy 21). Professor Dazzi is the academic leader of the stem cell transplantation programme and head of Stem Cell Biology Section at the Kennedy Institute of Rheumatology with which he holds a joint appointment. His interests are focussed on the role of mesenchymal stem cells in normal and pathological conditions. He is searching into the factors which affect stem cell recruitment and function and developing various strategies to use these cells for regenerative medicine in degenerative and inflammatory diseases and to exploit their immunosuppressive properties in transplantation and autoimmunity. He has strong collaborative links with the Departments of Pathology (Prof Terence Cook) and Renal Medicine (Prof Charles Pusey) at the Hammermith and with University College at the Royal Free Hospital (Prof Hans Stauss and Prof Stephen Mackinnon).
Paroxysmal Nocturnal Haemoglobinuria (PNH) is an acquired clonal disorder of the haemopoietic stem cell (HSC) in which a mutation affects the X-linked gene PIG-A. Dr Tassos Karadimitris is currently investigating the potential role of CD1d-restricted, GPI-specific T cells in the pathogenesis of PNH.
