Identifying better therapies for patients with myelodysplastic syndromes.

Research Opportunity
Masters by Research
Department / Centre
Medicine
Location
St Vincent's Institute of Medical Research
Primary Supervisor Email Number Webpage
Professor Louise Purton lpurton@svi.edu.au 03 9231 2480 Personal web page
Co-supervisor Email Number Webpage
Dr Jessica Holien jessica.holien@rmit.edu.au 03 9925 7256

Summary In this project you will determine the effects of potential therapies for a pre-leukaemic disease called myelodysplastic syndromes. You will learn different techniques including flow cytometry, cell culture, drug studies and develop an understanding of blood cell production and blood-forming stem cells.

Project Details

We make billions of blood cells every day. In the adult, haematopoiesis (the ongoing formation of blood cells from haematopoietic stem cells (HSCs)) occurs via self-renewal vs differentiation decisions of the HSC. Deregulation of HSCs can result in blood cell diseases (including cancers).

By altering the expression of the two different protein forms of Hoxa1 in mouse bone marrow cells, we have developed two mouse models of a blood cell disease called myelodysplastic syndromes (MDS). MDS is a malignant blood cell disease that predominantly results in bone marrow failure in the patients, who die of complications of low blood cell counts. It is a very heterogeneous disease and approximately 30% of patients spontaneously progress to acute myeloid leukaemia. Aside from stem cell transplants (which the majority of patients are ineligible for due to their older age) there is no cure. The mechanisms underlying MDS are largely unknown, although recent studies have suggested that altered splicing of a gene (ie differences in the production of protein forms of the same gene) are causative of MDS. We have confirmed that the expression of the two HOXA1 transcripts are significantly deregulated in 50% of human MDS patients, making our mouse models very clinically relevant for the study of this disease.

We have recently performed an extensive drug screen using our MDS mouse cells to identify novel therapies that may benefit patients with MDS. In this Honours project some of the promising drugs that were identified as potential therapies will be tested using cells obtained from our MDS mouse models and MDS patient cells.

The studies will incorporate a range of different techniques used in HSC biology, including isolation of bone marrow cells from mice, fluorescence-based immunostaining accompanied by fluorescence activated cell sorting (FACS), molecular biology techniques, culture studies. We do not expect the student to have much (if any) background knowledge of HSC biology or stem cells.



Faculty Research Themes

School Research Themes

Cancer in Medicine



Research Opportunities

Masters by Research
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department / Centre

Medicine

Research Node

St Vincent's Institute of Medical Research

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