Targeted inhibition of the NUP98-NSD1 and NUP98-KDM5A fusion oncogenes in myelodysplastic syndromes and acute myeloid leukaemia models by NSD1 and KDM5A inhibitors (WP2)
Rationale and objectives
We will analyze the efficiency of epigenetic drugs as a mechanism to decrease aberrant histone methylation activity in myelodysplastic syndrome (MDS) and secondary acute myeloid leukaemia (sAML) driven by the fusion protein of NUP98 and the histone methyltransferase NSD1 (NUP98-NSD1) as well as the fusion protein of NUP98 and the histone lysine demethylase KDM5A (NUP98-KDM5A).
Our objectives are:
• To determine the effect of NSD1 and KDM5A inhibitors in murine and human cells with NUP98-NSD1 and NUP98-KDM5A, respectively, on the level of cell biology.
• To study the genome-wide patterns of histone modifications before and after the treatment in order to identify target loci.
• To understand the impact of NSD1 and KDM5A inhibition on intercellular heterogeneity performing single-cell RNA sequencing (sc-RNAseq)
Veterinärmedizinische Universität Wien (Austria, 4 months). Depending on the project development: Aelian Bio (Austria, 1 month).
PhD in Cell Biology, Autonomous University of Barcelona (UAB), Spain.