University Research Lecturer
I have received my undergraduate degree from the University of Milan (Italy), and I have obtained my PhD in Oxford in 2007 on the study of myeloid disorders using microarray technology.
My research has primarily concerned the investigation of the molecular pathogenesis of the myelodysplastic syndromes (MDS), a heterogeneous group of myeloid malignancies. We have performed the largest study to date of gene expression profiling in MDS CD34+ cells and this work has resulted in the identification of key dysregulated genes and pathways in this disorder. We have also identified a gene expression profiling-based signature for assessing prognosis in MDS. More recently we have explored the interconnections among mutations, gene expression, clinical variables and patient survival in MDS, and we showed that the transcriptome was the most powerful predictor of outcome. Our study of the MDS transcriptome using RNA sequencing has identified key downstream target genes that are aberrantly spliced in association with spliceosome gene mutations in MDS. Mutation of the splicing factor SF3B1 is strongly associated with the MDS subtype MDS-RS and we have implicated aberrant splicing of the downstream target gene ABCB7 in the pathophysiology of MDS-RS. In collaborative studies, we have shown that U2AF1 and SF3B1 mutations in myeloid malignancies induce oncogenic isoforms of IRAK4 that are therapeutically targetable (using the IRAK4 inhibitor CA-4948). These data have critical implications for understanding MDS phenotypic heterogeneity and support the development of therapies targeting splicing abnormalities.
Using next-generation sequencing technology, we have illuminated the molecular landscape of MDS and we have evaluated the frequency and chronology of mutation acquisition in serial samples from MDS patients progressing to acute myeloid leukaemia (AML).
We are currently using single-cell analysis to determine the transcriptomic changes occurring in the stem cell population of splicing factor mutant MDS, and CRISPR/Cas9 genome editing to model MDS and to investigate the impact of common mutations on the MDS phenotype.
I have served on several departmental committees and on international scientific panels, including the International Working Group for the Prognosis of MDS.