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- Nerlov Group: Hematopoietic Stem Cell Genetics Research Group
I am a Postdoctoral Research Scientist working in the group of Professor Claus Nerlov in the MRC Molecular Haematology Unit at the Weatherall Institute of Molecular Medicine (WIMM).
I received my PhD from the University of Milano Bicocca (Italy) 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 moved to Oxford in January 2014, when 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.
I moved to the WIMM in November 2015 to join the group of Professor Claus Nerlov.
My main research interest is to determine the cellular and molecular mechanisms underlying the age-dependent decline in red blood cell formation.
The hematopoietic system has the remarkable ability to provide a lifelong supply of mature cells that make up the entire blood and immune system. However, although the blood is the definitive self-renewing tissue of the body, it does not escape the detrimental effects of the aging process, manifested in human populations in the form of an increase in myeloproliferative diseases, declining adaptive immunity, and greater propensity to anemia.
Different studies have pointed toward intrinsic deficits in HSC function as important contributing factors behind hematopoietic decline and malignancy during aging. While HSC aging has been extensively explored, the mechanisms of how aging alters the ability of the bone marrow micro- environment to support and maintain HSCs is only recently being investigated. In fact, new studies show that HSC aging is driven by both cell-intrinsic and cell-extrinsic mechanisms.
The purpose of my project is to understand the cellular and molecular mechanisms underlying the decline of erythropoiesis during ageing, determining the contributions to this process of both the hematopoietic and stromal component of the hematopoietic system.
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
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
Application of CRISPR/Cas9 genome editing to the study and treatment of disease.
Pellagatti A. et al, (2015), Arch Toxicol, 89, 1023 - 1034