- About
- Strategic Plan
- Structure
- Governance
- Scientific divisions
- ACRF Cancer Biology and Stem Cells
- ACRF Chemical Biology
- Advanced Technology and Biology
- Bioinformatics
- Blood Cells and Blood Cancer
- Clinical Translation
- Epigenetics and Development
- Immunology
- Infectious Diseases and Immune Defence
- Inflammation
- Personalised Oncology
- Population Health and Immunity
- Structural Biology
- Ubiquitin Signalling
- Laboratory operations
- Funding
- Annual reports
- Human research ethics
- Scientific integrity
- Institute life
- Career opportunities
- Business Development
- Partnering opportunities
- A complete cure for HBV
- A stable efficacious Toxoplasma vaccine
- Activating SMCHD1 to treat FSHD
- Improving vision outcomes in retinal detachment
- Intercepting inflammation with RIPK2 inhibitors
- Novel inhibitors for the treatment of lupus
- Novel malaria vaccine
- Precision epigenetics silencing SMCHD1 to treat Prader Willi Syndrome
- Rethinking CD52 a therapy for autoimmune disease
- Targeting minor class splicing
- Royalties distribution
- Start-up companies
- Partnering opportunities
- Collaborators
- Publications repository
- Awards
- Discoveries
- Centenary 2015
- History
- Contact us
- Research
- Diseases
- Cancer
- Development and ageing
- Immune health and infection
- Research fields
- Research technologies
- People
- Anne-Laure Puaux
- Associate Profesor Ian Majewski
- Associate Professor Aaron Jex
- Associate Professor Alyssa Barry
- Associate Professor Andrew Webb
- Associate Professor Chris Tonkin
- Associate Professor Daniel Gray
- Associate Professor Diana Hansen
- Associate Professor Edwin Hawkins
- Associate Professor Emma Josefsson
- Associate Professor Ethan Goddard-Borger
- Associate Professor Grant Dewson
- Associate Professor Isabelle Lucet
- Associate Professor James Murphy
- Associate Professor James Vince
- Associate Professor Jason Tye-Din
- Associate Professor Jeanne Tie
- Associate Professor Jeff Babon
- Associate Professor Joan Heath
- Associate Professor Justin Boddey
- Associate Professor Kate Sutherland
- Associate Professor Leanne Robinson
- Associate Professor Marco Herold Marco Herold
- Associate Professor Marie-Liesse Asselin-Labat
- Associate Professor Matthew Ritchie
- Associate Professor Melissa Davis
- Associate Professor Misty Jenkins
- Associate Professor Nawaf Yassi
- Associate Professor Oliver Sieber
- Associate Professor Peter Czabotar
- Associate Professor Rachel Wong
- Associate Professor Rhys Allan
- Associate Professor Rosie Watson
- Associate Professor Ruth Kluck
- Associate Professor Sandra Nicholson
- Associate Professor Sant-Rayn Pasricha
- Associate Professor Seth Masters
- Associate Professor Sumitra Ananda
- Associate Professor Tim Thomas
- Associate Professor Wai-Hong Tham
- Associate Professor Wei Shi
- Catherine Parker
- Chela Niall
- Deborah Carr
- Dr Alisa Glukhova
- Dr Anna Coussens
- Dr Ashley Ng
- Dr Ben Tran
- Dr Bernhard Lechtenberg
- Dr Brad Sleebs
- Dr Drew Berry
- Dr Gemma Kelly
- Dr Gwo Yaw Ho
- Dr Hui-Li Wong
- Dr Jacqui Gulbis
- Dr Joanna Groom
- Dr John Wentworth
- Dr Kelly Rogers
- Dr Lucy Gately
- Dr Margaret Lee
- Dr Mary Ann Anderson
- Dr Maryam Rashidi
- Dr Matthew Call
- Dr Melissa Call
- Dr Philippe Bouillet
- Dr Rebecca Feltham
- Dr Samir Taoudi
- Dr Shalin Naik
- Dr Sheau Wen Lok
- Dr Simon Chatfield
- Dr Tracy Putoczki
- Guillaume Lessene
- Helene Martin
- Joh Kirby
- Kaye Wycherley
- Keely Bumsted O'Brien
- Mr Joel Chibert
- Mr Simon Monard
- Mr Steve Droste
- Ms Carolyn MacDonald
- Professor Alan Cowman
- Professor Andreas Strasser
- Professor Andrew Lew
- Professor Andrew Roberts
- Professor Anne Voss
- Professor Clare Scott
- Professor David Huang
- Professor David Komander
- Professor David Vaux
- Professor Doug Hilton
- Professor Gabrielle Belz
- Professor Geoff Lindeman
- Professor Gordon Smyth
- Professor Ian Wicks
- Professor Ivo Mueller
- Professor Jane Visvader
- Professor Jerry Adams
- Professor John Silke
- Professor Ken Shortman
- Professor Leonard C Harrison
- Professor Lynn Corcoran
- Professor Marc Pellegrini
- Professor Marnie Blewitt
- Professor Melanie Bahlo
- Professor Mike Lawrence
- Professor Nicos Nicola
- Professor Peter Colman
- Professor Peter Gibbs
- Professor Phil Hodgkin
- Professor Stephen Nutt
- Professor Suzanne Cory
- Professor Terry Speed
- Professor Tony Burgess
- Professor Tony Papenfuss
- Professor Warren Alexander
- Diseases
- Education
- PhD
- Honours
- Masters
- Undergraduate
- Student research projects
- A new regulator of stemness to create dendritic cell factories for immunotherapy
- Advanced methods for genomic rearrangement detection
- Control of cytokine signaling by SOCS1
- Defining the protein modifications associated with respiratory disease
- Delineating the pathways driving cancer development and therapy resistance
- Developing a new drug that targets plasmacytoid dendritic cells for the treatment of lupus
- Development and mechanism of action of novel antimalarials
- Development of a novel particle-based malaria vaccine
- Development of tau-specific therapeutic and diagnostic antibodies
- Discovering novel therapies for major human pathogens
- Dissecting host cell invasion by the diarrhoeal pathogen Cryptosporidium
- Epigenetic biomarkers of tuberculosis infection
- Essential role of glycobiology in malaria parasites
- Evolution of haematopoiesis in vertebrates
- Human lung protective immunity to tuberculosis
- Identifying novel treatment options for ovarian carcinosarcoma
- Interaction with Toxoplasma parasites and the brain
- Interactions between tumour cells and their microenvironment in non-small cell lung cancer
- Investigating the role of mutant p53 in cancer
- Microbiome strain-level analysis using long read sequencing
- Minimising rheumatic adverse events of checkpoint inhibitor cancer therapy
- Modelling spatial and demographic heterogeneity of malaria transmission risk
- Naturally acquired immune response to malaria parasites
- Predicting the effect of non-coding structural variants in cancer
- Structural basis of catenin-independent Wnt signalling
- Structure and biology of proteins essential for Toxoplasma parasite invasion
- T lymphocytes: how memories are made
- TICKER: A cell history recorder for longitudinal patient monitoring
- Targeting host pathways to develop new broad-spectrum antiviral drugs
- Targeting post-translational modifications to disrupting the function of secreted proteins
- Targeting the epigenome to rewire pro-allergic T cells
- Targeting the immune microenvironment to treat KRAS-mutant adenocarcinoma
- The E3 ubiquitin ligase Parkin and mitophagy in Parkinson’s disease
- The molecular controls on dendritic cell development
- Understanding malaria infection dynamics
- Understanding the genetics of neutrophil maturation
- Understanding the neuroimmune regulation of innate immunity
- Understanding the proteins that regulate programmed cell death at the molecular level
- Using cutting-edge single cell tools to understand the origins of cancer
- When healthy cells turn bad: how immune responses can transition to lymphoma
- School resources
- Frequently asked questions
- Student profiles
- Abebe Fola
- Andrew Baldi
- Anna Gabrielyan
- Bridget Dorizzi
- Casey Ah-Cann
- Catia Pierotti
- Emma Nolan
- Huon Wong
- Jing Deng
- Joy Liu
- Kaiseal Sarson-Lawrence
- Komal Patel
- Lilly Backshell
- Megan Kent
- Naomi Jones
- Rebecca Delconte
- Roberto Bonelli
- Rune Larsen
- Runyu Mao
- Sarah Garner
- Simona Seizova
- Wayne Cawthorne
- Wil Lehmann
- Miles Horton
- Alexandra Gurzau
- Student achievements
- Student association
- News
- Donate
- Online donation
- Ways to support
- Support outcomes
- Supporter stories
- Rotarians against breast cancer
- A partnership to improve treatments for cancer patients
- 20 years of cancer research support from the Helpman family
- A generous gift from a cancer survivor
- A gift to support excellence in Australian medical research
- An enduring friendship
- Anonymous donor helps bridge the 'valley of death'
- Renewed support for HIV eradication project
- Searching for solutions to muscular dystrophy
- Supporting research into better treatments for colon cancer
- Taking a single cell focus with the DROP-seq
- WEHI.TV
New clues about how our body guards against cancer
5 October 2018
Walter and Eliza Hall Institute researchers have uncovered a key factor protecting against age-related DNA damage, providing important clues about how our body guards against cancer.
research revealing new clues about how our body
guards against cancer.
The discovery was made by identifying a rare genetic mutation in three patients with an unusual, early-onset form of acute myeloid leukaemia (AML). The patients all lacked a DNA repair protein called MBD4, which led to them accumulating DNA damage at a higher rate than normal – as though they were ageing prematurely.
The research, led by Dr Edward Chew and Dr Ian Majewski in collaboration with Dr Mathijs Sanders and Dr Peter Valk at Erasmus University Medical Center, Netherlands, highlights the importance of DNA damage in driving cancer development. The study was published in the journal Blood today.
At a glance
- As we age, our DNA accumulates damage, which can increase our risk of developing cancer
- Our researchers identified accelerated DNA damage in rare cases of acute myeloid leukaemia, and linked this to loss of a DNA repair protein called MBD4
- This is the first time MBD4 has been implicated in blood cancer development, and provides important clues about why cancer becomes more common as we age
DNA damage drives cancer
All cancers are caused by changes to a cell’s genome, and many cancers become more common with age, said Dr Chew, who is a clinician PhD student at the Institute and a haematologist at The Royal Melbourne Hospital, a partner of the Victorian Comprehensive Cancer Centre.
“In this study, we identified AML samples from three patients that showed unusually high rates of ‘methylation damage’ to the DNA,” Dr Chew said. “DNA methylation has a role in fine tuning gene activity – but it also makes DNA more susceptible to damage.
“DNA damage occurs constantly and our cells have ways to correct this damage. This is how we safeguard our genome from accumulating damage that puts our cells at risk of cancerous changes.
“When we sequenced the patients’ genomes, we discovered they all carried changes in the same gene, called MBD4. This gene encodes a protein that repairs methylation damage. The loss of MBD4 in these patients explained why their cells had not repaired the damage,” he said.
AML is typically a disease of older adults, with the majority of patients aged more than 70.
“The three patients who lacked MBD4 were predisposed to accumulating high rates of methylation damage – which we believe led to them developing AML as young adults (around 30 years old),” said Dr Chew
New insights into DNA repair
that uncovered uncovered a key factor protecting against
age-related DNA damage. (L-R) Dr Zhen Xu,
Dr Edward Chew, Dr Rebecca Bilardi, Dr Christoffer
Flensburg, Ms Sarah Miller and Dr Ian Majewski
Methylation damage accumulates as part of normal ageing, but this study highlighted a particularly strong link with blood cancers, Dr Majewski said.
“We were looking at extreme cases where young individuals had accumulated abnormally high levels of methylation damage, driving the development of AML unusually early in life – it was as though their cells were ageing prematurely,” he said.
“Our research pinpoints methylation damage more generally – even at lower levels – being an important contributor to the development of cancers. An important next step is to understand precisely why blood cells are at risk from this form of DNA damage.”
The research discovery relied on recent advances in the fields of genomics and computational biology.
“One of the three AML samples we studied was collected in the 1990s,” said Dr Majewski. “At that time, DNA sequencing was still cumbersome and expensive, and we still hadn’t completed the first human genome sequence. We were lucky that our colleagues in the Netherlands had the foresight to store this sample for future analysis.
“It’s exciting that we’ve now been able to use modern technologies to unravel this mystery, and in the process we’ve gained important new insights into how the ageing process shapes the development of cancers,” Dr Majewski said.
The research was supported by generous donations from the Alfred Felton Bequest, Mr Malcolm Broomhead, and BHP Billiton, as well as grants from the Australian National Health and Medical Research Council, the Leukaemia Foundation of Australia, the Sultanate of Oman, the Bellberry-Viertel Fellowship, the Netherlands Organisation for Scientific Research, Center for Translational Molecular Medicine (Netherlands), the Victorian Cancer Agency, and the Victorian Government.
Media enquiries
Super Content:
Want to hear about our latest discoveries? Subscribe to our supporter newsletter, Illuminate.