Promising child cancer researchers supported by Balnaves Foundation
November 11, 2015
Two inspiring postdoctoral researchers from Children’s Cancer Institute, Dr Daniel Carter and Dr Duohui (Vincent) Jing, are recipients of the 2015 Balnaves Foundation Young Researcher’s Fund. The Balnaves Foundation, a private philanthropic organisation set up by Neil Balnaves AO in 2006, has awarded each researcher $100,000 to explore uncharted territory in childhood cancer.
Dr Carter will be exploiting new ‘single-cell profiling’ technology to seek out effective drug targets in neuroblastoma, the most common ‘solid tumour’ in children. Dr Jing will examine the 3D structure of DNA in white blood cells to determine which children with acute lymphoblastic leukaemia (ALL), the most common childhood cancer, will respond to standard treatment, and which children will not.
Their approaches are very different, but by describing the early stages of disease at a detailed molecular level, both researchers have the potential to uncover vital clues that could lead to more effective treatments.
Dr Carter will attempt to isolate the descendants of the very first nerve cells to become cancerous in neuroblastoma. The genetic makeup of these original cells, as yet unknown, will help explain exactly how neuroblastoma develops and how best to tackle it with drugs.
“Prior to single cell profiling technology, we had to examine the whole organ where neuroblastoma forms, and could only average the genetic profile across hundreds of millions of cells,” said Dr Carter.
“Single cell analysis now allows us to determine the exact genetic makeup of separate cells. The pressing question for me is: what differentiates a cell that may have a kind of pre-cancer characteristic – but is essentially harmless – from one that can actually transition and evolve into an advanced cancer?”
“There is one marker that appears to distinguish between the harmless cells and their more lethal counterparts – and that is what I will be examining in this project.”
“In developing new therapies against neuroblastoma, you would obviously want to target the lethal cells – clones or offspring of the original ‘pre-cancer’ cells – because they continue to drive the cancer.”
Dr Jing will be applying emerging knowledge about the structure and regulation of DNA to the treatment of acute lymphoblastic leukaemia.
There is currently a ‘standard protocol’ for treating patients with leukaemia. Every patient is treated with ‘glucocorticoids’ for one week and their response determines what the next treatment step will be. Poor response to glucocorticoids indicates a less promising outlook, and results in much more aggressive chemotherapy treatment.
Glucocorticoids have been used for decades. They target ‘glucocorticoid receptors’ in DNA, which bring about cell death, although no-one understands exactly how.
Dr Jing recently discovered that patients who respond well to glucocorticoids during the first week of treatment have an open DNA structure at a specific location, while patients resistant to chemotherapy have a closed DNA structure at the same location.
Around 2 metres of DNA is tightly folded and compacted into the nucleus of every cell in our body. Depending on how the DNA is folded, certain genes will be on the surface, allowing them to be activated – just as an open flower can be pollinated.
There are also ‘regulatory regions’ of the genome that influence the function or fate of genes – and their effect can be likened to the actions of birds or insects that aid or hinder pollination.
“In my recent study I found one region of DNA that responded to glucocorticoids, and with this Balnaves grant I intend to see how many others I can find,” said Dr Jing.
“What I hope to find is a ‘gene signature’, or cluster of genomic regions with an open configuration, that indicate sensitivity to chemotherapy.”
“I will also be looking for differences in the regulatory regions of the genome – because these can produce different outcomes even in patients whose DNA structure looks similar.”
By finding gene signatures that predict a leukaemia’s response to treatment, Dr Jing hopes to spare children the side effects of glucocorticoid chemotherapy.
Through its generous support, The Balnaves Foundation is providing the opportunity for Dr Carter and Dr Jing to progress their work to a stage where it might be published and has a reasonable chance of attracting peer-reviewed funding.
“Peer reviewed funding from various government bodies is becoming increasingly competitive each year, edging out some promising early career scientists who have not yet had time to establish the impressive track records they need,” said Hamish Balnaves, General Manager of the Balnaves Foundation.
“We are therefore delighted to be able to give at least some of these talented young people a chance to prove themselves – and potentially make a finding that will save people’s lives.”
Photograph (left to right): Dr Vincent Jing, Mr Hamish Balnaves and Dr Dan Carter
About The Balnaves Foundation
The Balnaves Foundation is a private philanthropic organisation established in 2006 by Neil Balnaves AO to provide support to charitable enterprises across Australia.
Dispersing over $2.5 million annually, the Foundation supports eligible organisations that aim to create a better Australia through education, medicine and the arts with a focus on young people, the disadvantaged and Indigenous communities.
About Children’s Cancer Institute
Originally founded by two fathers of children with cancer in 1976, Children’s Cancer Institute is the only independent medical research institute in Australia wholly dedicated to research into the causes, prevention and cure of childhood cancer. Forty years on, our vision remains unchanged – to save the lives of all children with cancer and to eliminate their suffering. The Institute has grown to now employ more than 220 researchers, operational staff and students, and has established a national and international reputation for scientific excellence.
Our focus is on translational research, and we have an integrated team of laboratory researchers and clinician scientists who work together in partnership to discover new treatments which can be progressed from the lab bench to the beds of children on wards in our hospitals as quickly as possible. These new treatments are specifically targeting childhood cancers, so we can develop safer and more effective drugs and drug combinations that will minimise side-effects and ultimately give children with cancer the best chance of a cure with the highest possible quality of life.
We are currently leading the establishment of the Zero Childhood Cancer national child cancer personalised medicine program for children with the most aggressive cancers, in partnership with the Sydney Children’s Hospitals Network. This program will revolutionise the way treatment decisions are made, with the aim of improving survivorship for those children at highest risk of treatment failure from their disease.