Breaking Through: SBI Researchers Earning the Spotlight

Research Spotlight

March 2025

At Systems Biology Ireland, our research spans multiple disciplines and cancer types, leveraging big data and advanced omics technologies, combined with computational modelling, to deepen our understanding of complex biological systems. We take pride in seeing our researchers share their findings and gain recognition at national and international events. Their innovative approaches are contributing to shaping the future of healthcare. Below are some examples of their work.

Dr Luke Jones (Postdoctoral Researcher) recently earned the Overall Best Postdoctoral Researcher Poster Prize at the 2025 Irish Association for Cancer Research (IACR) Conference where he presented research on using structure-based, dynamic modelling to identify effective drug combinations in acute myeloid leukaemia (AML). This type of modelling approach involves the use of computational models to look at the 3D shapes of molecules such as a proteins or drugs and predict how they move and interact over time. Dr Jones and colleagues founds that mutations activating RAS signalling are common in AML and are associated with poor outcome. RAS is like an "on/off switch" inside your cells that helps control how cells grow, divide, and survive. When the RAS switch is turned on at the right time, it helps your cells grow and function properly; however, when RAS is over-activated cells can grow and divide uncontrollably contributing to the development of cancer.

Using the modelling approach referenced above, Dr Jones identified synergistic combinations of RAF inhibitors that effectively reduced RAS pathway activity. RAF is a protein that is part of the same signalling pathway as RAS i.e. the RAS-RAF-MEK-ERK pathway. When RAS is “on,” it binds to and activates RAF. It’s like a molecular "domino effect" that controls cell growth, division, and survival.

The predictions from the above computational model were validated in vitro and in vivo, including patient-derived xenograft models. The study highlights the power of computational modelling in predicting effective drug combinations and underscores the potential of RAF inhibitor-based therapies for RAS-mutant AML, paving the way for improved treatment strategies with enhanced clinical relevance. It should be noted that Dr Jones also won the Irish Cancer Society Senior Researcher of the Year Award in 2024 for his work on AML.

Dr Mary O’Reilly (PhD Student & Medical Oncology Registrar) was awarded the Conquer Cancer Merit Award at the 2025 ASCO Gastrointestinal Cancer Symposium for her research on clinical management of colorectal cancer in an Irish healthcare setting, using the Oncomine targeted DNA sequencing panel.

Early-onset colorectal cancer (CRC) affects individuals under 50 and may have distinct molecular signatures compared to late-onset CRC. In this study, Dr O’Reilly and teams in St Vincent's University Hospital and Systems Biology Ireland analysed the genetic and clinical characteristics of early-onset and late-onset CRC. This study revealed that the patients with early-onset CRC have distinct mutational profiles compared with their older counterparts. Dr O’Reilly’s research highlights the significance of routine next generation sequencing mutation panel analysis in CRC management, emphasising its role in guiding personalised treatment strategies, especially for patients who experience a relapse of disease.  The findings were (opens in a new window)published as part of the ASCO Symposium proceedings in the Journal of Clinical Oncology.

Theodora-Ioana Grosu (PhD Student) was shortlisted as a finalist for the Prof. John Fitzpatrick Medal at the 2025 Irish Association for Cancer Research (IACR) Conference. Theodora studies the effects of EZH2 loss in paediatric T-cell Acute Lymphoblastic Leukemia (T-ALL), a blood cancer that affects white blood cells, i.e. T-cells, involved in the immune system.

EZH2 is a protein made from a gene called Enhancer of zeste homolog 2. Its main job is to work as part of a team called Polycomb Repressive Complex 2 (PRC2) to turn off certain genes by “packing” the DNA so only the right genes are active. This process of turning off genes is important for normal functions like cell growth and repair. But when EZH2 gets behaves abnormally, it can lead to the wrong genes being activated, helping cancer cells grow and resist treatment.

Approximately 25 percent of children who have T-ALL have alterations in the genes that make EZH2 and its partners. These changes are especially common in a more aggressive form of T-ALL, known as Early Thymic Precursor (ETP)-ALL, which is known to be more resistant to treatment. Despite this, we do not know why the changes in EZH2 and PRC2 make treatment less effective in (ETP)-ALL.

To dig deeper, Theodora and her colleagues used a technique called RNA sequencing to look at how the loss of EZH2 affects gene activity, since its main funciton is to silence genes. They were able to determine that without EZH2, cells activate genes that are typical for ETP-ALL, rather than T-ALL, which could explain the resistance to treatment seen in this group of patients. Since EZH2 normally “packs” these genes in order to keep them inactive, the team hypothesised that its absence may make the DNA more open and therefore activate the genes in the wrong ways.

The team are now working on mapping these changes in detail. Understanding how EZH2 contributes to chemoresistance in T-ALL can lead to better treatments and improved outcomes for children with this cancer.