Landsteiner lecture by Alan Warren | Ribosome dysfunction in bone marrow failure and leukaemia

On 7 April 2025, Prof Alan Warren PhD (University of Cambridge, UK) will give a Landsteiner Lecture at Sanquin Research.

Title: Ribosome dysfunction in bone marrow failure and leukaemia

Host: Despoina Trasanidou

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Abstract
Ribosomes are the essential molecular nanomachines that make all cellular proteins. Pathogenic germline variants in genes encoding ribosomal proteins or ribosome assembly factors cause a group of human diseases known as ribosomopathies that are characterized by bone marrow failure and an increased risk of haematological malignancies. In this lecture, I will discuss our work in dissecting the molecular mechanisms of ribosome assembly using single particle cryo-electron microscopy. I will show how convergent somatic evolution from early in life offsets the deleterious effects of a germline ribosome defect but paradoxically, increases the risk of clonal evolution to haematological malignancy

Biography
Dr. Alan Warren is Professor of Haematology at the University of Cambridge, UK. His research laboratory is based in the Cambridge Institute for Medical Research. Warren gained his PhD in the laboratory of Dr. Terry Rabbitts at the LMB where he discovered that the LIM-only protein Lmo2 is required for haematopoiesis. In recent work, his lab has made the surprising discovery that the inherited leukaemia predisposition disorder Shwachman-Diamond syndrome (SDS) is a “ribosomopathy” that is caused by impaired maturation of the large ribosomal subunit. This work has provided fundamental new insight into the process of ribosome assembly, stimulating a new field addressing how defective ribosome biogenesis subverts haematopoietic stem cell function to cause bone marrow failure and leukaemia predisposition.