17 April 2020

Master Thesis project in the Porse Group

Cancer Stem Cell/ Translational Hematology

Characterization of aberrant hematopoietic stem cell populations in myeloid malignancies

The Porse group at DanStem (PTH) is looking for a highly motivated and enthusiastic MSc student. Any experience in flow cytometry, single cell RNA sequencing and bioinformatics data analysis will be highly appreciated but it is not mandatory. The project will be carried out in the lab of Bo Porse at the Finsen laboratory (also affiliated with the Biotech Research and Innovation center (BRIC) and the Danish Stem Cell Centre (DanStem)), located at the 3rd floor at the Biocenter.

Background: Hematopoietic stem cells (HSCs) are cells resident in the Bone Marrow (BM) and are responsible for maintaining formation of all effector cells of the blood throughout life. Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are two different hematologic disorders where we know that hematopoietic Stem cells play a key role, especially in the relapse or recurrence of the diseases. Despite their importance, these MDS-HSC and pre-leukemic HSC (pl-HSC) remain poorly characterized due to the lack of a technology that allows for their physical separation and characterization from normal HSCs.

The project: You will be joining an experienced 3rd year PhD student in the project of identification and characterization of these stem cells using state-of-the-art single-cell RNA sequencing technology established in the laboratory called TARGET-seq. This technique will allow us to describe for the 1st time the gene expression profiles of aberrant HSCs and use these to identify molecular pathways that can be targeted in disease treatments. Using this technique, we will process bone marrow samples from patients diagnosed with low risk MDS and then progressed to AML to identify the different clones that took over the BM and caused the progression. Finally, you will be able to use some of these finding to further validate potential targets in vitro understanding the molecular mechanism of these pre-leukemic mutations.

Methods used: Single Cell RNA sequencing, Target-Seq, Flow Cytometry, Handling Human Samples

Keywords: HSCs, Acute Myeloid Leukemia, myelodysplastic syndromes, single cells, mutations