BSc, MSc, PhD
Senior postdoctoral researcher
My research is focused on the role of recurrent mutations observed in myelodysplastic syndrome (MDS). MDS represents a heterogeneous group of clonal hematopoietic stem cell (HSC) malignancies characterized by ineffective haematopoiesis leading to peripheral blood cytopenias, and MDS patients show increasing bone marrow blasts.
Over the last 10 years, next generation sequencing has revolutionized our understanding of the pathogenesis of this disease, establishing that MDS arises through the sequential acquisition of somatic mutations in HSCs. A large number of driver mutations have been identified in MDS, and the affected genes can be organized into a number of categories including RNA splicing factors, epigenetic regulators, cohesion components, transcription factors, DNA damage response and signal transduction.
We are using the latest technologies to investigate the role of these mutated genes in MDS. CRISPR/Cas9, a novel genome editing tool has transformed research in molecular biology and we are currently using this technique to investigate the impact of driver mutations on the MDS phenotype. Furthermore, we are using CRISPR/Cas9 together with induced pluripotent stem cells to model MDS. These studies will allow for the determination of the impact of these mutations, both individually and in combination, on the MDS phenotype and for the identification of the critical downstream targets in the main cell lineages affected in MDS.
I am currently the departmental Deputy Biological Safety Officer and also the health and safety officer of Bloodwise Molecular Haematology Unit.
SF3B1 mutations induce R-loop accumulation and DNA damage in MDS and leukemia cells with therapeutic implications.
Singh S. et al, (2020), Leukemia
Application of induced pluripotent stem cell technology for the investigation of hematological disorders.
Dolatshad H. et al, (2019), Adv Biol Regul, 71, 19 - 33
The U2AF1S34F mutation induces lineage-specific splicing alterations in myelodysplastic syndromes.
Yip BH. et al, (2017), J Clin Invest, 127, 2206 - 2221
Cryptic splicing events in the iron transporter ABCB7 and other key target genes in SF3B1-mutant myelodysplastic syndromes.
Dolatshad H. et al, (2016), Leukemia, 30, 2322 - 2331
Application of genome editing technologies to the study and treatment of hematological disease.
Pellagatti A. et al, (2016), Adv Biol Regul, 60, 122 - 134