Kay Kendall Leukaemia Fund Intermediate Research Fellow
Haematology- Leukaemia- Ageing- Haematopoietic stem cells- Haematopoietic niche
I am a KKLF Intermediate Research Fellow based in the Professor Claus Nerlov group in the MRC Molecular Haematology Unit at the Weatherall Institute of Molecular Medicine (WIMM).
I obtained my PhD in Experimental Haematology from the University of Milan in 2014. During my PhD I worked under the supervision of Professor Carlo Gambacorti-Passerini and my research was focused on the characterization of atypical Chronic Myeloid Leukemia (aCML), a heterogeneous disorder belonging to the group of myelodysplastic/myeloproliferative (MDS/MPN) syndromes. By using exome sequencing approach, we discovered SETBP1 as a novel oncogene and identified specific mutations of this gene in patients affected by aCML.
I then moved to the University of Oxford, where I joined Professor Jacqueline Boultwood group (Bloodwise Molecular Haematology Unit/ Nuffield Division of Clinical Laboratory Sciences) as a postdoctoral scientist to elucidate the function of ASXL1, a gene commonly mutated in myeloid malignancies including CML. There, I developed a special interest in the new powerful genome editing CRISPR/Cas9 tool that I used to correct the ASXL1 homozygous nonsense mutation present in the CML cell line KBM5, resulting in protein re-expression with restored normal function.
In November 2015 I joined Professor Claus Nerlov group in the MRC Molecular Haematology Unit at the WIMM. Over the last four years, my research has been focused mainly on understanding the cellular and molecular mechanisms underlying the decline of erythropoiesis during ageing, determining the contributions to this process of both the haematopoietic and stromal component of the haematopoietic system.
In July 2019 I was awarded a prestigious Kay Kendall Leukaemia Fund Intermediate Fellowship for three years at the Weatherall Institute of Molecular Medicine. My research goal is to investigate the effects of the ageing bone marrow microevironment in the prognosis of acute myeloid leukaemia (AML). I will specifically examine how the ageing microenvironment influences Leukemic Stem Cells behaviour contributing to their increased chemo-resistance and/or disease re-initiation after therapeutic intervention in elderly.
This work will allow me to identify new drug targets that may be used to improve treatment strategies for AML in the elderly.
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
C/EBPα and GATA-2 Mutations Induce Bilineage Acute Erythroid Leukemia through Transformation of a Neomorphic Neutrophil-Erythroid Progenitor.
Di Genua C. et al, (2020), Cancer Cell, 37, 690 - 704.e8
Application of genome editing technologies to the study and treatment of hematological disease.
Pellagatti A. et al, (2016), Adv Biol Regul, 60, 122 - 134
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
ASXL1 mutation correction by CRISPR/Cas9 restores gene function in leukemia cells and increases survival in mouse xenografts.
Valletta S. et al, (2015), Oncotarget, 6, 44061 - 44071