Supervisor View Full Details 2nd

• genetics, genomics and molecular biology
• cancer/oncology
• Other

Paediatric; Haematology; Leukaemia; Epigenetics

• Medicine
• Paediatrics
• Pathology

• Adolescent medicine
• Haematology
• Oncology

Our research is co-located at Systems Biology Ireland (SBI) in UCD and Children's Health Ireland (CHI) at Crumlin. Our aim is to unravel the molecular pathogenesis of high-risk childhood and adolescent leukaemias and lymphomas using systems biology approaches. We are particularly interested in understanding how acquired somatic genetic alterations alter leukaemia biology and outcome (for recent examples see PMID 31940477, 30655366, 29950694, 28605290, 28196984).

Our main current focus is working out the downstream molecular effects of mutations and deletions in epigenetic factors, using a combination of in vitro cell line experiments and computational modelling. Co-location in the National Paediatric Haematology Oncology service at CHI means that our research is tightly tied to the clinic, helping us to ask relevant scientific questions that are important for patient care. These links also mean that we are well placed to extend our analyses to primary leukaemia samples at CHI and under the framework of international clinical trials. For example, I sit on the scientific committee and chair the Biobanking committee of the ALLTogether01 study, which will be the largest childhood leukaemia trial ever undertaken (2500 cases/year across Europe).

There is scope to accommodate a range of potential projects, but these should fulfil three criteria:
1) The project addresses an important clinical question in childhood and adolescent blood cancer.
2) The project incorporates systems biology approaches.
3) The project includes provision for in vivo confirmation of the relevance of experimental findings.

Our current research revolves around transcriptional, epigenetic and proteomic analyses of in vitro cell line models that have been generated using CRISPR/Cas9 genomic editing techniques that are up and running in the lab. These approaches are readily applicable to effectively all molecular alterations that are seen in paediatric leukaemias and lymphomas. Results of these analyses (e.g. RNA-seq, proteomics, ChIP-seq) are incorporated into computational models, and SBI’s specific expertise in this field gives an investigative advantage that is not available in the majority of leukaemia research laboratories.

In particular, we are keen that our research is heavily informed by clinical integration in a bedside-bench-bedside model. We firmly believe that advances in patient care must be driven by clinicians who fully appreciate the transformative potential of modern scientific approaches. We think our research programme would be very suitable for a prospective clinician scientist in paediatric haematology/oncology who wishes to tackle the most difficult issues in childhood and adolescent cancer.