B Cell Development in Health and in Disease

Dr Simon Wagner has a clinical interest in B-cell chronic lymphocytic leukaemia (CLL) which leads naturally to its laboratory focus on B-cell development. The regulation of B cell terminal differentiation is crucial to the development of a normal immune response. The transcription factor BCL-6 is essential for this process and its likely mechanism of action is to modulate the effects of the STAT family of transcription factors. The current projects of his laboratory include the identification of BCL-6 target genes, the analysis of cis-acting control regions for BCL-6 and the utilisation of a novel systematic approach to identify compounds which disrupt the effects of BCL-6 and which may form lead molecules for drug discovery.

Multiple myeloma is also a malignancy of the terminally differentiated B-cell that has devastating but largely poorly understood effects on the integrity of bone remodelling in affected patients. Dr Amin Rahemtulla and Dr Evangelos Terpos have an active research group investigating the pathogenesis of bone destruction in multiple myeloma and the role of apoptotic pathways in myeloma biology. This work is closely linked to a large and active clinical research programme in myeloma involving autologous and allo-SCT, and novel phase I/II agents.