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Akbar Shahid

Post-doctoral Fellow

Research Interests

My research focuses on the epigenetic drivers involved in the development of secondary acute myeloid leukaemia (s-AML), which refers to a leukaemic process either resulting from prior myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), or aplastic anaemia with or without treatment, or due to previous radiation or chemotherapy exposure for another cancer.  

I am specifically focusing on the progression of MPN and MDS into s-AML, both of which are regarded to be clonal haematopoietic stem cell disorders. The lack of standard of care and effective therapies, highlighted by certain s-AML patients only surviving 4 weeks from time of progression, warrants an urgent need to better understand this disease at the molecular and cellular level.  

Briefly, by using state-of-the art genetic engineering models, including an inducible CRISP-Cas9 system, I aim to better understand how certain oncogenic mutations (including genes such as TET2, EZH2, DNMT3A and TP53) impact chromatin modifications at different stages of progression from MPN/MDS to s-AML. The impact of each knockout or mutation on haematopoietic processes such as self-renewal and differentiation will be assessed, in-conjunction with in-depth epigenetic characterisation by assessing DNA methylation (whole-genome TAPS), protein:DNA interactions (Chip-Seq) and chromatin accessibility (ATAC-seq), to which the results will be mapped with gene expression data (RNA-seq).  Results will be validated in longitudinal samples from MPN or MDS patients evolving to s-AML.

Ideally, this would allow for the potential identification of a particular network of genes associated with progression to s-AML in which promoter and/or enhancer methylation is deregulated resulting in either inappropriate activation or inhibition of the respective pathway, which could be targeted therapeutically.  

Background

I completed my PhD in Medicine in September 2022 at the University of St Andrews, School of Medicine, under supervision by Professor David Harrison. My PhD focused on understanding alternative polyadenylation (APA) and mitochondrial metabolism of de novo acute myeloid leukaemia (AML) and how these processes were altered when perturbed with a novel adenosine analogue.

Recent publications

More publications