PhD Candidate Profile: Peter Truong

Peter Truong photo

What is your research about?

Myelodysplastic Syndromes (MDS) represents a highly heterogeneous group of haematological disorders manifested as some combination of low red blood cell production, low platelet production, low white blood cell production, and high propensity of transformation towards Acute Myeloid Leukemia (AML) due to dysfunctional bone marrow. MDS ranks as one of the most prevalent blood malignancies with current annual estimates of 10 cases per 100,000 persons. This incidence rate increases 5-fold for patients over the age of 70 and is expected to increase over time due to an aging population.

 Allogeneic bone marrow transplants remain the only curative option for MDS. However, this procedure carries the risk of graft-versus-host disease and is extremely toxic for older patients. Azacitidine (AZA), a cytidine analogue, is the most efficacious treatment option and is approved for all subtypes of MDS. AZA is not a cure for MDS but results have shown that half of the patients treated with AZA respond within 4-6 months and may not progress towards AML. However, for those patients that do respond to AZA, most relapse within two years for obscure reasons. For the other half, there are few alternatives and the molecular mechanisms underlying their resistance remains mysterious. There is currently a need to identify non-responders early on in treatment, as the logistics of AZA can further exacerbate the patient’s disease due to receiving ineffective medication for six months.

To improve upon this “wait and see” approach and to understand why patients relapse, we need to first understand why non-responders are resistant to AZA and how AZA mediates its effects in MDS patients. For my PhD, I aim to identify drug resistant signatures in MDS cells through performing a genome-wide CRISPR screen.

What is translational application of your research?

With the approval of AZA for treatment of MDS more than a decade ago, it is not well understood on how AZA mediates its effects in MDS patients. As such, this research project was commissioned to help revolutionize current MDS treatment standards. Through this genome-wide CRISPR screen, the goal is to identify molecular pathways that dysplastic and malignant haematopoietic cells use to evade drug sensitivity. By understanding the pathways that sensitize these dysplastic cells to AZA, we can leverage these molecular targets to perform data driven drug testing to identify alternative compounds that are effective in AZA resistant MDS patients. Taken together, this project will have significant translational implications on optimizing MDS treatment standards by predicting early on which patients may be resistant to AZA by evaluating gene signatures in their malignant cells, and developing combination therapies that would improve AZA sensitivity in AZA resistant patients for better clinical outcome.

How would the TCRN PhD top-up Scholarship help you succeed?

The TCRN scholarship will greatly support my PhD by providing me with additional resources to attend relevant conferences where I can present my research and network with other scientists that specialize within my line of research. Furthermore, this scholarship will provide me with networking opportunities within the TCRN network and access to professional TCRN workshops.