#IDIBELLseminars: Blood stem cell dysfunction and onset of marrow failure in GATA2 deficiency

Inherited bone marrow failure associated with heterozygous mutations in GATA2 predisposes individuals to haematological malignancies, but the mechanisms of disease progression remain poorly understood. Using cellular and zebrafish models, we are investigating the mechanistic basis for loss of stem cell fitness, onset of marrow failure, and disease progression in GATA2 deficiency. Through cellular models for mechanistic insights and zebrafish models for genetics and single-cell transcriptomics, we identified a role for GATA2 in preventing DNA damage and maintaining stem cell fitness. A CRISPR F0 functional screen of GATA2 targets has uncovered eight new regulators of HSPC function that may contribute to the onset of marrow failure in GATA2 deficiency. Our results establish a potential mechanism underlying bone marrow failure in GATA2 deficiency and open new avenues for intervention in this disease.

Hosted by Alessandra Giorgetti – Hematopoietic stem cell biology and leukemogenesis group

Dr Rui Monteiro is an Associate Professor at the Department of Cancer and Genomic Sciences, University of Birmingham, where he established his lab in 2018. He has a diploma in Biochemistry from the University of Lisbon and a PhD in Developmental biology from the University of Utrecht (Hubrecht Institute), The Netherlands, under the supervision of Prof Christine Mummery. His postdoc was carried out at the Weatherall Institute of Molecular Medicine in Oxford, supervised by Prof Roger Patient, where he specialized in developmental haematopoiesis using the zebrafish model. His lab is interested in blood stem cell formation in embryonic development and in understanding the defects underlying blood stem cell dysfunction in bone marrow failure syndromes, using in vitro and in vivo (zebrafish) models.