Dr. Alan Warren

Biography

Alan Warren obtained his undergraduate degrees in Biochemistry (1983) and Medicine (1986) from the University of Glasgow. He completed his PhD in Molecular Biology in 1995 under the supervision of Dr. Terry Rabbitts at the MRC Laboratory of Molecular Biology, where he discovered the LIM-only protein Lmo2, which is required for haematopoiesis. He is currently a Professor of Haematology at the University of Cambridge, UK. His research focuses on myelodysplastic syndromes (MDS), a poorly understood group of acquired clonal stem cell disorders characterized by ineffective haematopoiesis with the propensity to progress to acute myeloid leukaemia (AML). Recent findings have linked the pathogenesis of both acquired and inherited forms of MDS to defective ribosome maturation, particularly in the context of Shwachman-Diamond syndrome (SDS), an autosomal recessive disorder caused by mutations in the highly conserved SBDS gene. This condition is associated with a substantial lifetime risk of developing MDS and/or AML, estimated at 30-40%. Warren's laboratory has solved the X-ray structure of the SBDS protein and discovered its requirement for a late cytoplasmic step in the maturation of 60S ribosomal subunits, establishing SDS as an important model for understanding the defects in ribosome maturation that impair haematopoietic stem cell function and promote the multi-step progression from MDS to AML. Future work aims to elucidate the detailed mechanism of action of SBDS and to test the hypothesis that the stem cell defects in SDS arise from p53 stabilization in response to ribosomal stress.

Research Interests

Experience