Our Researcher in Focus for September is Professor Jonathan Bond. Jonathan is the UCD Brendan Mc Gonnell Professor of Paediatric Molecular Haemato-Oncology based at Systems Biology Ireland and an Honorary Consultant Paediatric Haematologist at Children’s Health Ireland at Crumlin where he is involved in diagnostic and clinical trial activities. He is funded through the National Children’s Research Centre Leadership Award scheme which supports his Professorship at UCD and his research programme on childhood leukaemia – Using systems biology to improve the treatment of childhood leukaemia.
“We study blood cancers called leukaemias and lymphomas. These are the most common cancers in children worldwide. In Ireland, all paediatric patients with blood cancers are treated at Children’s Health Ireland at Crumlin, where 50-60 new blood cancers are seen every year. This accounts for about 25% of all cancers in Irish children and adolescents”.
Leukaemias arise when cells in the bone marrow undergo a change or mutation that leads to the overproduction of abnormal white blood cells. This overproduction suppresses the development of normal healthy blood cells leaving patients at high risk of infections and bleeding.
Fortunately, modern treatments for paediatric leukaemia are incredibly effective. “Previously, the outlook for patients with blood cancers was very poor. If untreated, leukaemias will overwhelm normal production of blood cells, which means patients can no longer fight infection or make red blood cells. Thankfully, modern therapies for blood cancers are now very effective, and over 90% of children with the most common form of leukaemia are now completely cured”.
Although outcomes for children with leukaemia have improved enormously, a number of issues still need to be addressed, most notably, the development of treatment resistant leukaemia in some children. “Most leukaemias are now completely cured, but there is still room for improvement. Some children have relapses of leukaemias that are difficult to treat. Also, cancer therapies can have side-effects that can occasionally be severe, especially in growing children and adolescents. It’s important that we try to make this better”.
The aim of Jonathan’s research programme is to identify how leukaemia cells mutate or “rewire” to become resistant to treatment. “The best way to improve treatments is to try to understand the reasons why they sometimes don’t work. This is not straightforward, as the ‘internal wiring’ of a leukaemia cell is very complicated. In fact, the leukaemia cell is very good at ‘rewiring’ itself to keep itself alive and to escape being killed by the therapies we currently give”.
Traditionally, researchers who study the development of treatment resistant leukaemia have focussed on the role of a single protein or gene. These types of analyses are limited as they don’t factor in the complex signalling networks within leukaemia cells that involve multiple proteins and genes working in concert.
In contrast, Jonathan and his research team perform in depth proteomic and genetic profiling and generate computational models of how these different components interact within the “rewired” leukaemia cell. “A huge number of factors are involved in this rewiring, which means that it’s very difficult to analyse without the help of a computer. We use a scientific approach called ‘Systems Biology’ to try and better understand this rewiring. This involves making computer models of the pathways that keep a leukaemia cell alive”.
By comparing treatment sensitive cells and treatment resistant leukaemia cells, Jonathan and his team hope to be able to identify the changes in these complex signalling networks that lead to the development of treatment resistant leukaemia. “We think that this will identify the hidden ‘Achilles’ heels’ in leukaemias that are currently resistant to treatment. Ultimately, we hope that this will help us find more precise and effective cures for children with blood cancers”.
Find out more about Jonathan’s research through the following links:
SBI website: https://www.ucd.ie/sbi/people/groups/bondgroup/