Myelodysplastic syndromes (MDS) are a disease group characterized by clonal hematopoietic stem and progenitor cell expansion and ineffective hematopoiesis that often progress to Acute Myeloid Leukemia (AML) (Sperling et al., Nature Reviews Cancer 2017). Therapeutic interventions by chemotherapy or allogeneic stem cell transplantation fail to eradicate MDS due to persistent MDS stem and progenitor cells (Tehranchi et al NEJM 2010; Dimitriou et al., Oncotarget 2016‎; Dimitriou et al., NEJM under revision). Hence, novel approaches to understand MDS pathogenesis are important for the design of curative therapies. Interestingly, recent RNA-sequencing approaches on mutated stem and progenitor cells indicated frequent disruption in regulation of mRNA metabolism for MDS patients (Pellagati et al., Blood 2018). During the Master thesis period, the prospective Master student will use a variety of molecular (CRISPR/cas9 and shRNA, RT-PCR, droplet digital PCR, CLIP-seq) and cellular methodologies (flow cytometry including proliferation and apoptosis assays, colony forming unit assays and other hematological readouts) with the specific aim to identify novel and deregulated post-transcriptional ribonucleoprotein networks in MDS stem and progenitor cells. We envision novel solutions and tools to treat the disease (MDS and secondary AML) in its origin, by understanding and manipulating the RNA dynamics of cancer stem cells.

The applicant should preferably have some lab experience and a background in molecular biology or biomedicine. Please contact marios.dimitriou@ki.se for additional details regarding the project and attach your CV including a description of your educational/research background.