MRC Molecular Haematology Unit
MRC Weatherall Institute of Molecular Medicine
My research focuses on dissecting the regulation of lineage commitment of haematopoietic stem cells (HSCs). HSCs are multipotent cells that can self-renew and regenerate while producing all types of blood cells to maintain the integrity of the haemaopoietic system, though not all HSCs are identical. Based on their in vivo lineage production, HSC clones with differential lineage output have been reported – some generate progenitors and mature cells of multiple lineages, while others only produce single lineage. These HSC subtypes may play distinct roles in unperturbed and stressed haematopoiesis. One example is that aged individuals often have increased myeloid cells and decsreased lymphoid production with deficient immune response, which could be partly due to the expansion of HSC clones that are biased towards myeloid production but less efficient to generate lymphoid cells. Thus, understanding the lineage dynamics of HSCs is a key to resolving the molecular mechanism that supports normal haematopoiesis.
I received a MSc in Molecular Medicine and a PhD in Cell and Molecular Biology, both from Imperial College London. During my PhD, I studied the role of the MLL gene in the regulation of HSC activity and the development of acute leukaemia. I completed my PhD training in 2016 and moved to Oxford for a postdoctoral position. My current project is to characterise distinct HSC subtypes in mouse model to better understand how lineage commitment is (epi)genetically programmed. I use both molecular tools (e.g. high throughput sequencing) and functional approahces (e.g. in vivo transplantation) to perform bulk and single cell analysis. Hopefully, this line of work will help to identify critical molecular pathways for lineage commitment that could be genetically targeted to reprogram HSCs for regenerative haematopoiesis and other therapeutic applications.
Micro-environmental sensing by bone marrow stroma identifies IL-6 and TGFβ1 as regulators of hematopoietic ageing.
Valletta S. et al, (2020), Nat Commun, 11