Induced pluripotent stem cells (iPSCs) as model systems to study hematological malignancies


   Institute of Cancer and Genomic Sciences

   Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Myelodysplastic syndromes (MDS) are a type of blood cancer originating at the level of haematopoietic stem/progenitor cells (HSPCs) and often progress to acute myeloid leukaemia (AML). Current therapies fail in 50-60% of patients, but how patients might be stratified to identify those likely to respond from those who fail therapy is not clear.

Work from my group has been at the forefront of an emerging literature demonstrating MYBL2 as a novel tumour suppressor, lost or downregulated in as many as 50% of high-risk MDS patients. Significantly, our data shows a role for MYBL2 in supporting double-strand break (DSB) repair in HSCs and consistently, MYBL2 deficiency in MDS patients correlates with a dysfunctional DSB repair kinetics.  

Our work and the unique critical tools we have developed, including induced pluripotent stem cells (iPSCs) from patients with MDS, provide the opportunity to address how MYBL2 deficiency in the stem and progenitor compartment influences tumour development.

This project will further investigate how MYBL2 levels influence genome instability in HSPCs and define the vulnerabilities this influence brings.

Methods: iPSCs cell culture and organoids, lentivirus, microscopy, DNA replication assays, DNA repair assays, -omics.

Lab website:

https://www.birmingham.ac.uk/staff/profiles/cancer-genomic/garcia-paloma.aspx

Biological Sciences (4)

Funding Notes

In addition to the appropriate university fee (UK or international postgraduate research rate) the student will be expected to provide a bench fee of £20K approx., due to the high cost of iPSC cultures and differentiation to HSPCs. PhD projects will be of a total of 4 years, with 3.5 years in the lab and 6 months for thesis write-up. Any time in the write-up only mode will only incur a minimal tuition fee.

Register your interest for this project



Where will I study?