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- Nerlov Group: Hematopoietic Stem Cell Genetics Research Group
Cristina Di Genua
I am a DPhil student, working under the supervision of Prof Claus Nerlov and Prof Adam Mead in the MRC Molecular Haematology Unit (MRC MHU) at the MRC Weatherall Institute of Molecular Medicine (MRC WIMM). My research project focuses on understanding how haematopoietic cells gain a clonal advantage in acute myeloid leukaemia (AML).
For AML to propagate leukaemic cells need to gain a competitive advantage over non-leukaemic cells. This is achieved by acquiring mutations that can collaborate to induce enhanced self-renewal and proliferation. Mutations in AML are acquired in a hierarchically organised fashion where pre-leukaemic mutations are acquired within haematopoietic stem cells (HSCs), whereas signalling mutations are late events acquired within downstream pre-leukaemic progenitor cells. Why certain mutations are pre-leukaemic, and acquired within the HSCs, compared to others, and the mechanism by which pre-leukaemic and secondary mutations collaborate are still poorly understood.
Utilising genetically engineered leukaemia models my aims are to:
1) Study the impact of mutations within the HSC and understand how this effects leukaemic development
2) Study mutations in combination to understand how the mutations interact, identify the key populations that propagate the disease, and characterise the cellular mechanisms of the population.
These studies could potentially identify novel mechanisms/pathways that could be exploited for targeted treatment in AML patients.
Prior to becoming a DPhil student I obtained a BSc (Hons) in Biology at the University of Nottingham. I then worked as a Research Technician at the Nuffield Department of Medicine, University of Oxford, in the Sinkins lab to facilitate the development of a Wolbachia-based control strategy for mosquito-borne diseases. I then became a Research Assistant in the Nuffield Division of Clinical Laboratory Sciences, University of Oxford, in the Boultwood lab studying the clonal evolution of myelodysplastic syndrome to AML.
Niche-mediated depletion of the normal hematopoietic stem cell reservoir by Flt3-ITD-induced myeloproliferation.
Mead AJ. et al, (2017), J Exp Med, 214, 2005 - 2021
DISRUPTION OF HAEMATOPOIETIC STEM CELL HETEROGENEITY IN A MOUSE MODEL OF MYELOPROLIFERATIVE NEOPLASM
Norfo R. et al, (2017), HAEMATOLOGICA, 102, 149 - 150
Targeted resequencing analysis of 31 genes commonly mutated in myeloid disorders in serial samples from myelodysplastic syndrome patients showing disease progression.
Pellagatti A. et al, (2016), Leukemia, 30, 247 - 250
Targeted resequencing analysis of 31 genes commonly mutated in myeloid disorders in serial samples from myelodysplastic syndrome patients showing disease progression
Pellagatti A. et al, (2016), LEUKEMIA, 30, 247 - 250
TARGETED RE-SEQUENCING ANALYSIS OF 31 GENES COMMONLY MUTATED IN MYELOID DISORDERS IN SERIAL SAMPLES FROM MYELODYSPLASTIC SYNDROME PATIENTS WITH DISEASE PROGRESSION
Pellagatti A. et al, (2015), LEUKEMIA RESEARCH, 39, S24 - S25