I am a postdoctoral researcher in Prof. Sten Eirik Jacobsen’s Haematopoietic Stem Cell Biology Lab, working also in collaboration with the labs of Prof. Claus Nerlov and Prof. Adam Mead. I received a MSc from the University of Lisbon in 2011 and a DPhil from the University of Oxford in 2016.
My research focuses on molecular and functional single cell analyses to study the clonal dynamics of normal murine haematopoiesis, with special focus on the differentiation pathway between haematopoietic stem cells (HSCs) and megakaryocytes/platelets.
I am also interested in stem cell research in the broader contexts of developmental biology, cell therapy, and regenerative medicine.
In my work I have used genetically altered mouse models, flow cytometry analysis, in vitro and in vivo functional assays, and molecular approaches to identify distinct subtypes of bone marrow HSCs which adopt a fate towards stable replenishment of restricted subsets of mature blood lineages, while still retaining the properties of long-term self-renewal and multipotency. Most notably, we have identified rare long-term self-renewing HSCs that adopt a fate restricted to the megakaryocyte/platelet-lineage tree. In contrast, we have not found another long-term self-renewing HSC class that contributes exclusively to any other single blood cell lineage. Platelet-biased and platelet-restricted long-term HSCs are characterized by expression of the megakaryocytic von Willebrand factor gene (Vwf), and the frequency of these HSC subtypes increases with age.
By unraveling the mechanisms underlying HSC differentiation pathways at the single cell level, we aim to pave the way for the development of therapeutic approaches that selectively target or expand distinct subtypes of HSCs with distinct functional properties.
Ezh2 and Runx1 Mutations Collaborate to Initiate Lympho-Myeloid Leukemia in Early Thymic Progenitors.
Booth CAG. et al, (2018), Cancer Cell, 33, 274 - 291.e8
Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells.
Carrelha J. et al, (2018), Nature, 554, 106 - 111
Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors.
Luis TC. et al, (2016), Nat Immunol, 17, 1424 - 1435
Primitive Embryonic Macrophages are Required for Coronary Development and Maturation.
Leid J. et al, (2016), Circ Res, 118, 1498 - 1511
Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells.
Grover A. et al, (2016), Nat Commun, 7