Download Partnering with QIMR Berghofer

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QIMR Berghofer is a fully
integrated biomedical research
and development centre
CONTENTS
RESEARCH WITH CONSEQUENCES..................................................4
QIMR BERGHOFER HISTORY..............................................................5
QIMR BERGHOFER: YOUR DEVELOPMENT PARTNER.......................6
RESEARCH PROGRAMS.....................................................................9
Cancer Program..........................................................................10
Infectious Diseases......................................................................32
Mental Health/Complex Disorders ...............................................48
RESEARCH AND TECHNOLOGY PLATFORMS.................................61
TISSUE BANKS..................................................................................63
YOUR PARTNER IN Q-GEN...............................................................65
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RESEARCH WITH
CONSEQUENCES
QIMR Berghofer is dedicated to discovering and translating
research to the clinic locally and internationally.
Some of the Institute’s research with consequence has included:
• establishing a system to test antimalarial drugs
in humans infected with malaria parasites and
began clinical trials testing effectiveness of drug
therapies for malaria;
• carrying out collaborative research activities with
institutes in China, India, Hong Kong, Vietnam,
UK, USA, European Union and New Zealand;
• attracting researchers from over 20 countries and
is actively recruiting worldwide for new talent to
occupy the expanded QIMR Berghofer;
• embarking on QSkin, the largest skin cancer
research study ever conducted in Australia;
• identifying a new target for treating aggressive
brain tumours, which will commence clinical trials
shortly;
• participating in a pilot study, releasing Wolbachia
infected mosquitoes in Cairns to test the
effectiveness against the spread of dengue fever;
• developing a simple blood test to monitor the risk
of contracting cytomegalovirus, a virus that often
infects the lungs and gastrointestinal tract after
transplantation;
• heading up the largest Australian study of asthma
genetics, and based on this, launched a two-year
trial of the use of a new medication in treating
asthma;
• using brain imaging to develop a stress test for
dementia, to predict the function of patients for
up to two years;
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• discovering a way to use insights to the way HIV
replicates to beat HIV, with a view to starting
animal trials shortly;
• supporting research, particularly in the area of
infectious diseases, of relevance to the Aboriginal
and Torres Strait Islander communities in its
research programs;
• identifying several new genes that increase
the risk and hence provide entry points to
understanding how pathologies occur in breast,
ovarian, prostate and bowel cancer, bowel
disease, melanoma, endometriosis, and myopia;
• launching Australia’s first study into lifestyle
factors that may improve outcomes for ovarian
cancer patients;
• playing a key role in the research behind a new
skin cancer drug now on the market;
• confirming new research linking non-melanoma
skin cancers to the use of sun beds;
• showing for the first time that heavy alcohol
consumption more than doubles the risk of a type
of oesophageal cancer;
• developing a new way to monitor the liver health
of cystic fibrosis patients;
• launching the QIMR Berghofer Melanoma and
Skin Cancer Research Centre; and
• launching the QIMR Berghofer Centre for
Immunotherapy and Vaccine Development.
QIMR BERGHOFER
HISTORY
QIMR Berghofer was the brainchild of Dr Edward Derrick, an
early Director of the Queensland State Health Department
Laboratory of Microbiology and Pathology.
Derrick’s work on Q fever, scrub typhus and
leptospirosis made him aware of the need for an
institute devoted to full-time research into infectious
diseases of northern Australia. It was largely through
Derrick’s persistence that the Queensland Institute
of Medical Research Act was passed by the
Queensland Government in 1945.
The Institute has grown steadily to embrace cancer
research and clinical sciences with over 600
scientists, students and support staff, now housed in
the Bancroft Centre, the Clive Berghofer Cancer
Research Centre and the recently opened research
facility.
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QIMR BERGHOFER: YOUR
DEVELOPMENT PARTNER
QIMR Berghofer is one of Australia’s largest and most
successful medical research institutes and the highest
ranked medical research institute in the Asia-Pacific region
according to the Nature Publishing Index.
Our 700 full time researchers, visiting scientists
and students are investigating the genetic and
environmental causes of nearly 40 diseases as well
as developing new diagnostics, better treatments,
and prevention strategies such as antibodies
and vaccines.
The Institute offers a wealth of partnership,
collaborative and commercial opportunities for
industry and governments. QIMR Berghofer has
the capacity to translate basic research from the
discovery phase, through product development,
scale-up, manufacture through to Phase I and II
clinical trials.
We have strategic alliances with research
institutes, hospitals, universities, not-for-profits
and commercial partners, including Australian and
international biotechnology and pharmaceutical
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companies. In particular, QIMR Berghofer is
interested in commercial partnerships to further
early stage technologies which have the potential to
rapidly develop into successful technologies.
Opportunities include:
• Collaborative and contract research
• Development and manufacture of novel
therapeutics
• Clinical trials
• Consulting
• Technology licences
• Start-up companies
• Business partnerships
DISCOVERY
CLINICAL TRIALS
QIMR Berghofer has world class research facilities
and laboratories including:
Q-Pharm Pty Ltd conducts:
• The Drug Discovery Group
• The Queensland Protein Discovery Centre
• The Centre for Immunotherapy and Vaccine
Development
DEVELOPMENT
QIMR Berghofer has the capability and resources to
carry out product development, including:
• Research models and cell banks
• State-of-the-art technologies and equipment
• Scientists with commercial experience
MANUFACTURING
Q-Gen is a cGMP facility that offers clean room
facilities, state-of-the-art equipment, experienced
service and support.
• Phase I and II clinical trials,
• Pharmacokinetic studies,
• Bioequivalence studies, and drug analysis.
In order to facilitate the translation of QIMR
Berghofer’s research into clinical practice, Q-Pharm
is a related entity with QIMR holding a 24.5%
share. Q-Pharm is a specialist contract research
organisation that conducts early phase clinical trials
of pharmaceutical and biotechnology products
spanning the areas of therapeutic, diagnostic and
disease prevention agents.
The company offers the best appointed early
phase clinical trials facilities in Australasia, including
recruitment and outpatient clinics, a specialised
18-bed clinic for the conduct of the most medically
demanding trials and an open plan 24 bed facility
for larger healthy volunteer trials.
Q-Gen is licensed by the Therapeutic Goods
Administration (TGA) for the maintenance and
storage of working cell banks, the storage on site
of cellular products and the management and
release of cellular therapies for humans. The TGA
license makes Q-Gen one of a very small number of
organisations in Australia able to store human and
nonhuman samples under GMP conditions.
Q-Gen is one of the largest GMP facilities in
Australia, with 13 ISO Class 7 clean rooms. Each
clean room is fully equipped for the manufacture of
clinical therapies.
Q-Gen provides QIMR Berghofer with a unique
facility to conduct its translational research and
processes for clinical therapies and is currently
utilised in the manufacture of a number of
QIMR Berghofer sponsored developmental
immunotherapies and the production of material for
malaria trials.
Further information about Q-Gen can be found at
the end of this brochure.
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RESEARCH PROGRAMS
QIMR Berghofer is expanding our understanding, diagnosis and
treatment of some of the world’s most devastating diseases.
QIMR Berghofer’s research programs range from
identifying the environmental risks and genetic
basis of cancers as well as new therapeutics; to
developing better diagnostics and vaccines for
infectious diseases; to trialling biological controls for
mosquitoes to reduce the incidence of debilitating
diseases such as malaria and dengue fever.
The Institute takes a multi-faceted approach to
medical research. We have a strong international
reputation for our investigations into disease
genetics and epigenetics, immunology,
epidemiology, cellular function and infection. Our
use of immunotherapy, vaccines, protein and drug
discovery to develop new diagnostics and better
treatments is widely respected by the medical
community and industry.
FACILITIES:
Key research areas:
Cancer
Infectious diseases
• Genomics research
• Microarray and mass array analysis
• Transgenic and gene knockout mice
• Cancer and infectious disease mouse models
• Confocal and laser dissection microscopy
• FACS and cell sorting facilities
Mental health and
complex disorders
• PC2 animal facilities
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CANCER
PROGRAM
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Coordinator: Professor Georgia Chenevix-Trench
The Cancer Program looks closely at skin cancers, including melanoma;
hormone-related cancers, such as those of the breast, prostate, ovary
and endometrium; leukaemia and lymphoma, including exploring the
complications that can arise after transplantation; brain tumours; and
tumours of the gastrointestinal tract. A widely based interest in metastases is
found in many of the cancer research groups.
Laboratories within the Cancer Program work on identifying the genetic,
epigenetic and environmental risk factors underlying an individual’s cancer
risk; studying the molecular changes that occur in precursor lesions that can
give rise to cancer and those that occur during the formation of a tumour
and its subsequent metastasis; and developing and testing novel therapies
for cancer in the laboratory and clinical trials.
By working with clinical oncologists, pathologists and biobanks, members of
the Cancer Program are leading or part of large international consortia and
making great advances into the understanding of the genes that predispose
individuals to many types of cancer.
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Antigen Presentation and Immunoregulation
Group Leader: Dr Kelli MacDonald
The Antigen Presentation and Immunoregulation Laboratory aims to investigate how donor and host antigen
presenting cells (APCs) respond following bone marrow stem cell transplantation (SCT). Basic research in
immunology using pre-clinical models follows three streams: APC development, antigen presentation, and
APC induced T cell responses and their regulation. Importantly, these studies should lead to the development
of new therapeutic protocols that can be translated to clinical practice to improve transplant outcome.
CONDITIONS RESEARCHED
• Graft-versus-host disease
• Chronic liver disease
• Leukaemia, lymphomas and myelomas
CURRENT RESEARCH
• Contribution of donor dendritic cells to
immunosuppression which occurs following
haematopoeitic stem cell transplantation
• Development of DC immunotherapy protocols
for the attenuation of graft versus host
disease (GVHD)
• Role of IL-17 and related family members in
chronic GVHD
• Role of macrophages in GVHD
• Contribution of regulatory T cells to the
development of chronic GVHD
RECENT HIGHLIGHTS:
• Received NHMRC Project grant funding to study
the role of MMP-9-expressing macrophages in
chronic liver disease
• Identified for the first time a CD8+FoxP3+
regulatory T cell (Treg) population that develops
following stem cell transplantation and is highly
effective in suppressing graft-versus-host disease.
Furthermore, the group has developed strategies
to specifically expand this population in vivo,
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highlighting the capacity to manipulate this
population to control graft-versus-host disease
post transplant.
• Demonstrated that immune-suppression in
graft-versus-host-disease results from corrupted
antigen presentation post transplant.
• Identified non-haematopoietic APC responsible
for the induction of graft-versus-host disease
post transplant.
Bone Marrow Transplantation
Senior Scientist: Professor Geoff Hill, Department Coordinator: Immunology
The Bone Marrow Transplantation Laboratory uses pre-clinical transplant models to dissect the immunological
mechanisms of transplant rejection and aims to improve patient outcome through new therapies to prevent
and treat graft-versus-host disease. Research focuses on pathways of alloreactivity leading to graft-versushost disease and graft-versus-leukaemia (GVL) effects. The ultimate aim is to generate testable therapeutic
interventions that attenuate graft-versus-host disease and improve GVL.
CONDITIONS RESEARCHED
• Graft-versus-host disease
• Leukaemia, lymphoma and myeloma
CURRENT RESEARCH
• The interleukin-17 family of cytokines as
mediators of transplant outcome
• The treatment of steroid refractory acute GVHD
with CD52 targeted Ab and TNF antagonists
• Mechanisms of antigen presentation after
transplantation
• The use of type I interferons in preclinical and
clinical BMT to improve the eradication of
leukaemia.
• Immunological mechanisms of leukaemia and
myeloma eradication after transplantation
• Administration of an IL-6R antibody to prevent
GVHD in clinical bone marrow transplant
(BMT) recipients
• The use of suicide gene-transfected effector after
clinical haplo-identical BMT
• The use of induced regulatory T cells to treat
clinical chronic GVHD
RECENT HIGHLIGHTS:
• Defined the type of cells involved in antigen
presentation after bone marrow transplantation.
• Defined IL-6 as a major pathological cytokine
during graft-versus-host disease.
• Characterised a new regulatory T cell subset.
• Characterised type I interferon as the major
cytokine controlling anti-leukaemia effects after
BMT.
• Characterised defects in immune function
induced by graft-versus-host disease.
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Cancer Aetiology and Prevention
Team Head: Associate Professor Rachel Neale
The Cancer Aetiology and Prevention team covers three broad research areas: causes and management
of pancreatic cancer; role of vitamin D in human health; and causes and management of non-melanoma
skin cancer.
CONDITIONS RESEARCHED
• Pancreatic cancer
CURRENT RESEARCH
• D-Health - vitamin D clinical trial
• QPCS - Queensland pancreatic cancer study
RECENT HIGHLIGHTS:
• Awarded a grant to conduct trial of vitamin D
supplementation in 25,000 Australian adults.
• Published a paper showing that we can predict
vitamin D deficiency with reasonable accuracy.
This has led to a new grant application to validate
this tool.
• Published for the first time an association
between human papilloma viral load and risk of
cutaneous squamous cell carcinoma.
Cancer and Population Studies
Senior Scientist: Professor Adele Green AC
The Cancer and Population Studies Group aims to understand the causes of cancer and how to better
prevent and manage cancer. The group investigates the roles of environmental and personal factors in the
causation of cancer and its precursors, and in cancer prognosis. The group collaborates with clinicians,
statisticians and behavioural scientists and also with laboratory scientists to better understand the underlying
mechanisms of carcinogenesis. Particular focuses currently are cancers of the skin and of the colon.
The group aims to assess the contributions of personal factors (including psychological and social needs) and
environmental factors to quality of life, disease prognosis and survival in patients with early stage, invasive
cutaneous melanoma in Queensland, Australia.
CONDITIONS RESEARCHED
• Bowel (colorectal) cancer
• Melanoma
• Pancreatic cancer
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• Skin cancer (basal cell carcinoma and squamous
cell carcinoma)
CURRENT RESEARCH
• Primary Melanoma Project - Quality of Life Study
• Dietary Factors and Actinic Skin Damage
• Association between human papilloma virus and
squamous cell carcinoma (SCC) of the skin
• Study of genetic and environmental risk factors
for pancreatic cancer
• Exploring the causal pathways to cutaneous
melanoma
• 20 year follow-up study of the Nambour Skin
Cancer Project
• Working after Cancer Study - Quality of Life Study
RECENT HIGHLIGHTS:
• Showed that people with naevi (moles) on
the arms are more likely to develop basal cell
carcinomas than those without.
• Published a chapter on the epidemiology
of melanoma in the major US textbook on
women’s health.
• Contributed insights into the role of nutrients
in the causation of basal cell carcinoma and
squamous cell carcinoma.
• Showed that the prevalence of weekend sunburn
is still high in Queensland especially in young
male adults.
• Validated the use of skin surface microtopography
as a measure of skin photoaging in people aged
40 and over, though not past age 70 years.
• Published evidence from a randomised trial
that sunscreen can slow the prevention of skin
photoaging changes.
Cancer Control
Group Leader: Professor David Whiteman, Department Coordinator: Population Health
The Cancer Control Group has two major areas of research focus: melanoma and skin cancer; and upper
gastrointestinal neoplasia. In addition, the Group Leader is also a co-investigator on projects investigating
pancreatic, thyroid, cervical and liver cancer.
The group has primary strength in epidemiological approaches to the study of cancer. Historically, the focus
has been directed towards cancers of two main organ systems: the skin, and the gastro-intestinal tract.
The group’s largest enterprise currently is the QSkin study, a prospective cohort study of more than 43,000
Queenslanders to be followed up for the next 10 years. In 2012-13, the group completed the first data
linkages to external health registers to capture skin cancer events in the QSkin population.
CONDITIONS RESEARCHED
• Melanoma
• Pancreatic cancer
• Oesophageal cancer and Barrett’s oesophagus
• Skin cancers
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CURRENT RESEARCH
• QSkin - the world’s largest study of melanoma
and skin cancer
• InterSCOPE - the International Collaboration on
HPV and Oesophageal Cancer
• PROBE-Net - the Progression of Barrett’s
Esophagus Network
• BEACON: The Barrett’s Oesophagus and
Adenocarcinoma Consortium
RECENT HIGHLIGHTS:
• Awarded $2.5 million for a NHMRC Centre of
Research Excellence.
• Completed data linkage for the QSkin study.
• Developed models to describe the incidence
of oesophageal adenocarcinoma in the
Australian population.
• Published more than 10 publications in the
past year.
Cancer Drug Mechanism
Team Head: Dr Glen Boyle
The recently formed Cancer Drug Mechanisms Group combines expertise in cancer biology with drug studies.
The group’s work on cancer biology currently focuses on understanding the development and progression of
cancers of the skin and oral cavity. Specifically, the group is investigating the molecular mechanisms involved
in the progression and metastasis of melanoma, head and neck cancer, as well as cutaneous squamous cell
carcinoma. These molecular mechanisms also impact on drug resistance of cancers. The identification and
understanding of aberrantly regulated pathways in these cancers is crucial prior to the design or identification
of suitable agents to treat these diseases.
CONDITIONS RESEARCHED
• Melanoma
• Oral cancer
• Head and neck cancer
• Cutaneous squamous cell carcinoma
CURRENT RESEARCH
• Activities of specific melanoma transcription
factors that impact on drug resistance.
• Molecular profiling and biomarker identification in
head and neck cancers (including squamous cell
carcinoma with perineural invasion).
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Cancer Genetics
Group Leader: Professor Georgia Chenevix-Trench
The Cancer Genetics Laboratory investigates why some people get cancer, and how these cancers,
particularly those of the breast, ovary and stomach, develop from a normal cell. The laboratory also looks at
why these cancers are often found together in the same families and share many similar characteristics.
CONDITIONS RESEARCHED
• Breast cancer
• Gastric cancer
• Ovarian cancer
CURRENT RESEARCH
• Understanding germline variation underlying
individual differences in risk of breast and
ovarian cancer
• Genes involved in response to chemotherapy in
patients with ovarian cancer
• Evaluation of the role of the telomerase
gene, TERT, in susceptibility to breast and
ovarian cancer
• Next generation sequencing approaches to
finding novel breast cancer susceptibility genes
• Somatic mutations in basal-like breast tumour,
and in brain metastases
• Identification of the gene for gastric
adenocarcinoma and proximal polyposis of the
stomach (GAPPS syndrome) by exome and
genome sequencing
RECENT HIGHLIGHTS:
• Completed the first analyses of the largest cancer
genetics experiment ever undertaken.
• Identified nine new ovarian cancer risk loci.
• Shown that women from breast cancer families
who do not carry mutations in BRCA1 or BRCA2,
but instead are in the top quartile of polygenic
risk, have a risk of developing contralateral breast
cancer that is similar to that of a BRCA2 mutation
carrier.
• Demonstrated that the polymorphisms at the
TERT gene that underlie breast and ovarian
cancer risk are usually distinct from those
associated with telomere length.
• Developed mouse models of breast-to-brain
metastasis and shown that an activating mutation
in the EGFR gene can render a tumorigenic
breast line capable of colonising the brain.
• Identified 49 genetic polymorphisms associated
with risk of breast cancer.
• Demonstrated in mouse models of the efficacy
of anti-EGFR directed radioimmunotherapy
combined with radio-sensitising chemotherapy
and PARP inhibitor for the treatment of triple
negative breast cancer.
• Demonstrated the value of restoring DNA from
archival formalin fixed paraffin embedded tissues
for genomic profiling by SNP-CGH analysis.
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Cancer Immunoregulation
and Immunotherapy
Team Head: Dr Michele Teng
The Cancer Immunoregulation and Immunotherapy Group looks at tumour induced immune suppression,
Tregs, IL-23 and checkpoint receptors (PD-1/TIM-3/LAG-3).
CURRENT RESEARCH
• Inflammation-induced cancer and cancer
immunoediting
• The role of IL-23 family cytokines in tumor
immunity
• Tumor-induced immunosuppression
RECENT HIGHLIGHTS:
• Demonstrated that Tim-3 positive Tregs are
selectively enriched in tumours but not in the
periphery and therefore represent a novel target
for depletion.
• Demonstrated that skewing the balance between
IL-12/IL-23 can resolve nascent tumour in a de
novo mouse model of cancer.
Conjoint Gastroenterology
Laboratory Head: Professor Barbara Leggett
The main focus of the Conjoint Gastroenterology Laboratory is in understanding the molecular, histological,
clinical and epidemiological features of a particular class of polyps called serrated polyps, as well as the
cancers they may develop into. The group is studying a large series of colorectal polyps and cancers using
technologies to examine genome-wide changes in DNA methylation, gene expression and copy number
variation. The laboratory aims to identify molecular changes associated with high risk of polyp progression,
and to identify key pathways altered in colorectal cancer subgroups.
CONDITIONS RESEARCHED
• Colorectal cancer
CURRENT RESEARCH
• The role of the serrated polyp in colorectal cancer
• Existence of the serrated pathway of cancer
development by showing it is strongly associated
with activating mutations of the ontogeny BRAF
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• Discovering further genetic changes underlying
different subtypes of colorectal cancer
RECENT HIGHLIGHTS:
• Completed a proof of principle pilot DNA
methylation microarray project that identified
cancer subgroups based on BRAF and KRAS
mutation status, as well as identifying genes
hyper ethylated in these cancer subgroups.
• Described a new type of chromosomal instability
associated with BRAF mutation that is defined by
regional copy number variation.
• Reviewed over 6,000 bowel polyps to establish
the frequency of different polyp types and
identified a study population to examine the
molecular features of polyps at different stages
of progression.
• Commenced collaboration with QIMR Berghofer’s
Cancer and Population Studies Group to examine
epidemiological aspects of serrated polyp
development.
• Demonstrated that expression of the BRAF
V600E mutation in the adult mouse intestine
leads to hyperplasia, which likely equates to early
serrated polyp development.
Control of Gene Expression
Laboratory Head: Professor Frank Gannon, CEO and Director
The Control of Gene Expression laboratory has recently started at QIMR Berghofer, focussing on the control
of gene expression. The leader of the laboratory, Frank Gannon, has been active in this area of research for
many years, but had interrupted his research career when he took a position as Director General of Science
Foundation Ireland, the national funding agency in Ireland. He moved to Brisbane as the Director and CEO of
QIMR Berghofer in 2011 and now has established a research activity there.
The research of the group is designed to achieve a better understanding of the specifics of the control of
gene expression. The most recent research on which the current projects are built was the demonstration
of transient cyclical DNA methylation and demethylation (Kangaspeska et al., Nature 452, 2008). This work
followed from earlier detailed analysis of the processes by which the estrogen receptor recruited the RNA
polymerase and initiated transcription (Métivier et al., Cell 115, 2003; Métivier et al., EMBO reports 7, 2006).
A focus on histone modifications that occur in conjunction with the onset and silencing of transcription has
been the focus of the work of Dr Jason Lee who has joined the laboratory. His research activities grow from
the histone modification aspects through to the effects of modifying enzymes on other cellular targets and
their consequences in cellular physiology.
Whereas the focus of the group radiates from the estrogen receptor, the general questions of epigenetic
control of gene expression will be examined in diverse systems. In all cases the aim is to develop insights that
can be translated to different disease settings.
CONDITIONS RESEARCHED
• Breast cancer
• Endometrial cancer
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CURRENT RESEARCH
• Control of gene expression by ER in breast
cancer
• Impact of hypoxic environment on cancer
metastasis
• Epigenetic modification of DNA, histones and
other proteins
• The role of EphA3 methylation in glioblastoma
Drug Discovery
Group Leader: Professor Peter Parsons
The Drug Discovery Group combines expertise in cancer biology with genomics and drug discovery. Cell
communication networks in serious cancers reveal responses that provide opportunities for prevention
and treatment.
CONDITIONS RESEARCHED
• Head and neck cancers
• Oral cancer
• Melanoma
• Cutaneous squamous cell carcinoma
CURRENT RESEARCH
• Development of the novel anticancer
drug EBC-46
• Activities of specific melanoma
transcription factors
• Identifying plant compounds with potential for
addressing health problems other than cancer
• Molecular profiling and biomarker identification in
head and neck cancers (including squamous cell
carcinoma with perineural invasion)
RECENT HIGHLIGHTS:
• Confirmed that the efficacy of EBC-46 is due to
haemorrhagic necrosis.
• Discovered EBC-46-like molecules in other
plant species.
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• Noted first indications that the efficacy
of EBC-46 in vivo can be inhibited by
pharmacological agents.
Functional Cancer Genomics
Team Head: Dr Stacey Edwards
The Functional Cancer Genomics team is focused on post-GWAS (genome-wide association studies)
functional characterisation of breast and ovarian cancer genetics.
More than 60 different breast cancer risk loci and nine ovarian cancer loci have now been discovered via
GWAS, but until recently it has not been possible to identify the variants that are directly responsible for the
increased risk. Importantly, the majority of variants lie within non-coding regions of the genome and appear
to act as enhancers of genes through long-range interactions mediated by the formation of chromatin loops.
Over the last year, the team have developed a successful strategy for analysing these regulatory regions to
narrow down the candidate causative variants at each area and describe their likely actions in breast cancer.
CONDITIONS RESEARCHED
• Breast cancer
• Ovarian cancer
CURRENT RESEARCH
• Functional evaluation of novel long-range DNA
sequence elements that regulate the major breast
cancer genes, BRCA1 and BRCA2.
• Understanding how germline DNA variation
contributes to the risk of developing breast and
ovarian cancer.
• Genome-wide chromatin approaches to identify
novel target genes and the relevant changes in
their regulation that confer an increased risk of
cancer.
RECENT HIGHLIGHTS:
• Published paper in the American Journal of
Human Genetics; Functional Variants at the
11q13 Breast Cancer Risk Loci Regulate Cyclin
D1 Expression through Long-Range Enhancers.
• Published in Nature Genetics; Multiple
independent variants at the TERT locus are
associated with telomere length and risks of
breast and ovarian cancer.
• Authored paper in Nature Genetics; DNaseIhypersensitive exons co-localize with promoters
and distal regulatory elements.
• Published senior author review in Genes,
Chromosomes and Cancer.
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Functional Genetics
Team Head: Dr Juliet French
The Function Genetics Group is focused on the post-GWAS functional characterisation of breast and ovarian
cancer loci. In collaboration with geneticists at Cambridge and QIMR Berghofer the Group is fine-mapping
breast cancer loci to pinpoint the likely causal variants. The majority of variants fall in non-coding regions
of the genome suggesting the regulatory elements and non-coding RNAs are likely mechanisms of the
associated risk.
CONDITIONS RESEARCHED
• Breast cancer
• Ovarian cancer
CURRENT RESEARCH
• Understanding how genetic variants cause an
increase in risk of breast and ovarian cancer.
• Exploring the function of breast cancerassociated variants in long non-coding RNAs
• Understanding how the breast cancer
susceptibility gene, BRCA1 is regulated
RECENT HIGHLIGHTS:
• Authored a paper in Nature Genetics describing
the fine-mapping of the TERT locus for breast
cancer risk and functional follow-up.
• Published in American Journal of Human
Genetics describing the fine-mapping of the
genetic association at 11q13 and functional
follow-up.
Genomic Biology
Team Head: Dr Nicole Cloonan
Choice of chemotherapy has relied on data from populations rather than individuals, but the recently available
cancer genomic data shows that every cancer is different. To personalise therapy, doctors need to move
away from treating cancers based on where they develop in the body, and instead move towards treating
what has gone wrong in the cells of the individual patient.
Our current research focus is determining the relationship between miRNAs and drug sensitivity, with the short
term aim of using these as markers in personalised therapy, and the long term aim of using these as adjunct
chemosensitisers.
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CONDITIONS RESEARCHED
• Breast cancer
• Ovarian cancer
• Endometriosis
• Pancreatic cancer
• Lung cancer
• Schizophrenia
• Melanoma
CURRENT RESEARCH
• Decoding susceptibility to breast cancer
• Decoding miRNA regulated genetic circuits
• The role of BRCA non-coding mutations in breast
cancer susceptibility
RECENT HIGHLIGHTS:
• Identified the relationship between miRNAs and
EGRF inhibitor sensitivity.
• Identified novel biology behind miR-139’s link to
metastasis and migration function.
Gynaecological Cancers
Group Leader: Associate Professor Penny Webb
The Gynaecological Cancers Group investigates all aspects of cancer, particularly gynaecological cancer,
from aetiology to diagnosis, patterns of care, quality of life and survival. A particular focus is on the role of
environmental (non-genetic) factors and the interaction between genetic and environmental factors in the
causation of gynaecological cancer. More recently, this has extended to assessing how gynaecological
cancers are managed in Australia and investigating the role of lifestyle in determining quality of life and survival
after a diagnosis of cancer. Much of this work is conducted within three national population-based studies:
the Australian Ovarian Cancer Study (AOCS), the Ovarian Cancer Patterns of Care Study (POCS) and the
Australian National Endometrial Cancer Study (ANECS).
CONDITIONS RESEARCHED
• Endometrial cancer
• Ovarian cancer
CURRENT RESEARCH
• Improving Outcomes for Women with Endometrial
Cancer: Follow-up, Survival and Quality of Life
• Patterns of Care Study for Ovarian Cancer
• Molecular epidemiology of endometrial cancer:
the Australian National Endometrial Cancer Study
• Comparison of quality of life and standard endpoints of chemotherapy in advanced ovarian
cancer
• Quality of life and psychosocial predictors of
outcome in a population based study of ovarian
cancer
• Molecular epidemiology of ovarian cancer: The
Australian Ovarian Cancer Study (AOCS)
23
RECENT HIGHLIGHTS:
• Conducted an international pooled analysis
showing that obesity is associated with increased
risks of non-serous ovarian cancer, but does not
appear to increase risk of the most common and
most aggressive high-grade serous subtype.
• Observed that aspirin use may be associated with
a reduced risk of endometrial cancer, particularly
among obese women.
• Observed that only about one third of women
with ovarian cancer complete the recommended
six cycles of combination chemotherapy.
• Published a paper suggesting that although
obese women are at greatly increased risk of
endometrial cancer, if they lose weight their risk is
reduced again.
• Contributed to international pooled analyses
showing that tubal sterilization reduces risk of
ovarian cancer but smoking increases risk of the
mucinous subtype.
• Showed women with ovarian cancer report
needing ongoing assistance to deal with
psychological and physical needs over the first
two years after first-line treatment. Risk factors
for unmet needs included older age, advanced
disease, anxiety, depression, insomnia and lower
social support.
Immunology in Cancer and Infection
Senior Scientist: Professor Mark Smyth
The Immunology in Cancer and Infection Group study the immune reaction to cancer in mouse models and
cancer patients (most notably in multiple myeloma).
CURRENT RESEARCH
• Inflammation-induced cancer and cancer
immunoediting
• NK cell recognition of cancer and metastases
• Tumor-induced immunosuppression
• The role of IL-23 family cytokines in
tumor immunity
• Immunogenic cell death
• T and NKT cells in infection and cancer
• Combination immunotherapies for solid and
haematological malignancies
RECENT HIGHLIGHTS:
• Showed that CD73-deficient mice are resistant to
carcinogenesis.
• Demonstrated that NLRP3 promotes skin cancer
in mice.
• Identified that radiotherapy combines with
antibody-based immunotherapy in mouse models
of breast cancer.
• Showed that non classical MHC H2-M3
recognizes Ly-49A.
• Demonstrated that NK cells contribute to the premetastatic niche.
• Showed that IL-12 and IL-23 have opposing roles
in immune-mediated tumour dormancy.
24
• Showed that host immunity contributes to antimelanoma activity of Braf inhibitors.
Leukaemia Foundation of
Queensland Laboratory
Group Leader: Professor Andrew Boyd
The Leukaemia Foundation Group are investigating tumour-associated genes in cancer, in particular Eph,
ephrin and Nfib in leukaemia, sarcomas and brain tumours. The group’s research includes basic cancer
biology and development of targeted therapies.
CONDITIONS RESEARCHED
• Leukaemia
• Prostate cancer
• Spinal cord injuries
• Colorectal cancer
• Brain tumours (glioma, blastoma)
CURRENT RESEARCH
• Investigating the role of Eph and ephrin
membrane proteins in cancer
• Exploring the protein Fat1 as a candidate target
for new therapeutics
• Exploring the use of EphA4 inhibitors in spinal
cord injury
RECENT HIGHLIGHTS:
• Discovered the role of EphA3 in glioma.
• Identified EphA4 as a target in motor nerve injury
and disease.
Molecular Cancer Epidemiology
Group Leader: Associate Professor Amanda Spurdle
The Molecular Cancer Epidemiology Laboratory studies breast, ovarian, endometrial, colon and prostate
cancer, with a focus on identifying molecular signatures of normal and tumour tissue that can point to the
genetic and environmental causes of these cancers. The laboratory covers a range of projects with the
themes of cancer epidemiology and molecular pathology.
CONDITIONS RESEARCHED
• Breast cancer
• Colorectal cancer
• Ovarian cancer
• Prostate cancer
• Endometrial cancer
25
CURRENT RESEARCH
• The Australian National Endometrial Cancer
Study (ANECS)
• Breast and ovarian cancer predisposition and
prognosis and modifier genes
• Clinical classification of Mismatch Repair
gene variants
• Prostate cancer predisposition and
prognosis genes
• Clinical classification of BRCA1 and BRCA2
gene variants
• Breast and ovarian cancer predisposition and
prognosis and modifier genes
RECENT HIGHLIGHTS:
• Demonstrated that a BRCA1 variant with
intermediate functional activity are associated with
moderate risk of cancer.
• Applied five tier quantitative and qualitative
classification system to an international database
of MMR gene variants.
• Published a statistical model for classification of
variants in MMR genes.
• Investigated endometrial tumour features as
positive and negative predictors of germline MMR
gene mutation status.
• Demonstrated inadequacy of collection of family
history data in the clinical setting, and poor
referral of patients for genetic testing.
Oncogenomics
Senior Scientist: Professor Nick Hayward
The Oncogenomics Laboratory researches the genetics and genomics of melanoma, mouse models of
multiple endocrine neoplasia type 1 and the molecular genetics of Barrett’s oesophagus and oesophageal
cancer.
The laboratory is interested in investigating the process of cancer development at the level of individual cancer
predisposition genes, and by looking at the whole genome scale. Better understanding the genetic events
that cause cancer is hoped to lead to better ways of diagnosing or treating cancers in the future.
CONDITIONS RESEARCHED
• Melanoma
• Multiple endocrine neoplasia type 1
• Oesophageal cancer and Barrett’s oesophagus
CURRENT RESEARCH
• Studying melanoma susceptibility genes
• Studying the molecular genetics of MEN 1
(multiple endocrine neoplasia type 1)
• Identifying environmental and genetic risk factors
for oesophageal cancer and Barrett’s oesophagus
26
• Cellular and molecular changes that occur
in the progression of normal oesophageal
epithelium, through Barrett’s oesophagus, to
oesophageal cancer
RECENT HIGHLIGHTS:
• Helped identify a variant in the FTO gene
associated with melanoma risk in the
general population.
• Helped identify a recurrent activating ‘drug
targetable’ mutation in RAC1 that occurs in 5% of
sun exposed melanomas.
• Completed the largest and most comprehensive
genetic analysis of melanomas of unknown
primary, revealing insights into the origin of this
rare subset of tumours.
• Completed the first population-based
study of germline BAP1 mutations in uveal
melanoma cases.
• Helped show that a germline BAP1 splice
mutation in a family with uveal and cutaneous
melanoma also confers predisposition
to paraganglioma.
Radiation Biology and Oncology
Group Leader: Professor Martin Lavin
The Radiation Biology and Oncology Group is focuses on:
• Investigating the molecular basis of autosomal
recessive ataxias including ataxia-telangiectasia
(A-T) and ataxia oculomotor apraxia type 2
(AOA2);
• Early detection of prostate cancer; and
• Venomics-developing a serum tube for analyte
determination.
CONDITIONS RESEARCHED
• Ataxia-telangiectasia
• Blood cancers (leukaemia, lymphoma)
• Ataxia with oculomotor apraxia type 1 or 2
• Prostate cancer
CURRENT RESEARCH
The major area of research interest is centred on the genetics and biology of the human genetic disorder
ataxia-telangiectasia (A-T). Research areas include:
• Characterise rat models of ataxia-telangiectasia
(A-T)
• Complete the characterisation of the Setx-/mouse model and the role of senataxin in meiosis
• Investigate neurodegeneration in the rat models
• Investigate the role of senataxin in the cerebellum
• Generate induced pluripotent stem cells
(iPSC) from all patients attending the A-T clinic
in Brisbane
• Further characterise the role of SMG-1 protein in
inflammation and tumour development.
• Generate olfactory neuronal progenitor cells from
these A-T patients in collaboration with Professor
Alan Mackay-Sim, Griffith University
• Develop biomarkers for diagnosis and prognosis
in prostate cancer
• Complete work on the development of the
Q-Sera tube
• Investigate the role of ATM in DNA damage
response and in oxidative stress
27
RECENT HIGHLIGHTS:
• Generated the first stem cells from patients
with A-T.
• Produced two rat models for A-T.
• Generated first mouse model for ataxia
oculomotor apraxia type 2.
• Identified new autophosphorylation sites during
ATM activation.
• Demonstrated that ATM-dependent Rad50
phosphorylation is important in DNA repair and
cell cycle control.
• Demonstrated a novel role for SMG-1 protein in
stress granule formation.
• Cloned and characterised genes from a snake
venom gland.
Signal Transduction
Group Leader: Professor Kum Kum Khanna
The Signal Transduction Group’s major focus of research is on signalling pathways that maintain genome
stability during normal cell division cycle and in the face of DNA damage. The group seek to exploit
dysregulation of these pathways in breast cancer to develop new targeted therapeutic approaches.
CONDITIONS RESEARCHED
• Breast cancer
CURRENT RESEARCH
• To understand the role of Cep55 in cancer
initiation and progression using overexpression
mouse models
• To elucidate the pathophysiological role SSB1
and SSB2 using knockout mouse models
• To functionally characterise SSB1 and SSB2
interacting proteins
• To understand the role of Centrobin in the
regulation of microtubule dynamics
• To perform pathway profiling in breast cancer for
development of targeted therapies
• Development of novel combination treatments
against cancer in animal models including specific
pathway inhibitors and targeted drug delivery
• Understanding the cellular and molecular factors
which determine the extent of tumour response
to therapy including proliferation, apoptosis,
DNA-repair, and cell cycle.
RECENT HIGHLIGHTS:
28
• Developed a novel combination therapy
that prevents breast cancer recurrence in
preclinical models.
• Generated a mouse model of SSB1 and
uncovered its essential developmental role in the
regulation of skeletogenesis.
• Provided a mechanistic explanation as to
how KAP1 phosphorylation might regulate
heterochromatin repair.
• Contributed significantly to the development of
a therapeutic approach against glioblastoma;
radioimmunotherapy using anti-EphA3 antibody.
Tumour Micro-environment
Team Head: Dr Andreas Moller
The Tumour Microenvironment Team investigates how epithelial cancer cells interact with surrounding nontumour stromal cells to enable tumour progression and metastatic spread to distant tissues.
Work in the laboratory focuses on how low oxygen (hypoxic) environments and other stress conditions
experienced by tumours change the interaction and communication between the tumour cells and fibroblasts,
immune and endothelial cells, with a focus on three main processes crucial to tumour progression. Firstly, the
group is interested how tumour cells initiate new blood vessel formation (neo-angiogenesis) under hypoxia
and ways to prevent or alter these processes. Secondly, the laboratory investigates the mechanisms that
control epithelial to mesenchymal transition (EMT), an essential process for tumour cells to invade the stroma,
enter the vascular system and metastasise to distant tissues.
The third research topic of the laboratory centres around investigating how a hypoxic tumour can alter the
tissue of distant organs by modifying cell differentiation and behaviours to generate permissive environments
(pre-metastatic niches) at these sites. These pre-metastatic niches promote metastatic growth of
subsequently arriving tumour cells, and the aim is to translate findings into prognostic, diagnostic and curative
treatment options for cancer patients.
CONDITIONS RESEARCHED
• Breast cancer
• Lung cancer
CURRENT RESEARCH
• How do cancer-derived factors initiate and
maintain the pre-metastatic niche at distant sites?
• Can tumour-derived factors, which initiate the
pre-metastatic niche, be predictive or diagnostic
markers in breast or lung cancer?
• What is the role of Siah ubiquitin ligases (hypoxiainduced signalling mediators) in endothelial
cell function and blood vessel formation (neoangiogenesis).
RECENT HIGHLIGHTS:
• Investigated pre-metastatic niche induced by
tumour cell hypoxia.
• Found neo-angiogenesis is controlled by Siah
ubiquitin ligases.
• Determined the underlying mechanisms of premetastatic niche formation.
• Determined that the hypoxic response pathway in
breast cancer cells mediates pre-metastatic niche
formation in distant tissues.
• Identified that the hypoxia-regulator Siah controls
neo-angiogenesis in breast cancer.
29
Translational Leukaemia Research
Team Head: Dr Steven Lane
The Translational Leukaemia Research Team is researching myeloid blood cancers such as acute myeloid
leukaemia (AML), myelodysplastic syndrome (MDS) and the myeloproliferative neoplasms (MPN). These are
very aggressive and rapidly fatal blood cancers that are among the most common types of cancer affecting
Australians. The laboratory’s efforts are concentrated on understanding how leukaemia stem cells in AML and
MPN are able to regenerate leukaemia (or cause relapse in patients), even after cytotoxic chemotherapy. To
achieve this, research has focused on generating robust models of leukaemia and dissecting the pathways of
self-renewal in leukaemia stem cells and normal blood stem cells.
CONDITIONS RESEARCHED
• Blood cancers, including:
• Acute myeloid leukaemia
• Myeloproliferative neoplasm (polycythemia vera,
myelofibrosis, essential thrombocythemia)
• Myelodysplastic syndrome
CURRENT RESEARCH
Myeloproliferative neoplasms (MPN)
• Targeting disease-initiating stem cell populations
through targeted inhibitors of Jak2 signalling or
through inhibition of self-renewal pathways within
stem cell populations
Acute myeloid leukaemia
• Examining the effect of inhibitors used alone,
or in combination with chemotherapy on
the preferential dependency of AML stem
cells (compared to normal bone marrow) on
pathways regulating DNA damage response and
chromosomal stability
• Identifying novel LSC-specific targets that may be
of broader interest
Normal blood development
• Novel pathways that regulate blood stem cell
development
• Cytokine mobilisation of stem cells for use in
transplantation medicine
RECENT HIGHLIGHTS:
• Identified novel pathways of stem cell
mobilisation.
• Identified genetic susceptibilities of leukaemia
stem cells.
30
• Targeted disease-initiating stem cell populations
through targeted inhibitors of Jak2 signalling or
through inhibition of self-renewal pathways within
stem cell populations.
INFECTIOUS
DISEASES
32
Coordinator: Professor James Mccarthy
QIMR Berghofer’s Infectious Diseases Program studies how a range of
important pathogenic organisms cause illness, investigates improved
diagnosis and treatment techniques and develops vaccines to prevent
infections. The Program focuses its work on conditions that have major
impacts in the developing world and tropical regions.
The Program researches HIV, cytomegalovirus (CMV), Epstein-Barr virus
(EBV), mosquito-borne viruses; bacteria such as streptococci; and parasites
such as malaria, intestinal protozoa, worms and scabies.
Working closely with clinicians, other research institutes, and pharmaceutical
companies, the Infectious Disease Program aims to use strong
collaborations to improve the health of many.
QIMR Berghofer is a founding member of the Queensland Tropical
Health Alliance (QTHA), which is designed to enhance collaborations and
networking in tropical health issues, and the Australian Infectious Diseases
Research Centre (AID), which supports research into diseases such as
malaria, dengue fever and schistosomiasis. QIMR Berghofer’s collaboration
with James Cook University, Griffith University, QUT, and The University of
Queensland through the QTHA and again with the University of Queensland
though AID brings strength and focus for plans to address serious tropical
and infectious disease issues through Queensland, across Australia, and in
the Asia-Pacific region.
33
Bacterial Pathogenesis
Group Leader: Professor Sri Sriprakash
The Bacterial Pathogenesis Laboratory undertakes research into the two human pathogens Streptococcus
pyogenes and Streptococcus dysgalactiae subsp equisimilis. S. pyogenes is a leading cause of bacterial
related death in humans. Streptococcus dysgalactiae subsp equisimilis is a related species whose
contribution to disease is only now being understood. These two bacterial species cause a number of
diseases that target different organs in the body. The laboratory’s research is aimed at understanding the
pathogenic processes associated with infection by these organisms, and developing novel strategies to
prevent streptococcal disease.
The group also has a research interest in bacterial colonisation of medical devices. The insertion of a catheter
into a vein provides a portal by which bacteria can cross the skin and enter normally sterile body sites, thereby
causing disease. The group in interested in characterising the pathogenic and non-pathogenic species that
colonise these devices, identifying the sources of bacterial contamination, and ultimately developing novel
technologies or practices that reduce device colonisation.
CONDITIONS RESEARCHED
• Streptococcal disease (rheumatic fever,
rheumatic heart diseases, invasive diseases,
glomerulonephritis)
• Scabies
CURRENT RESEARCH
Bacterial Pathogenesis
• Molecular epidemiology and population genetics
of streptococci
• Development of novel group A streptococcal
vaccines
• Pathogenesis of streptococcal infections
• Characterisation of bacterial colonisation of
medical devices
Scabies
• Genes for SMIPP-Ss amplified in the scabies mite
genome to overcome host defence strategies
• The mechanism which protects the scabies mite
from complement-mediated gut damage
34
• Inhibition of host defences in mite burrows utilised
by bacterial pathogens such as GAS
RECENT HIGHLIGHTS:
• Found the population endemic for Streptococcus
pyogenes and S. dysgalactiae subsp equisimilis
colonisation exhibit increased recovery of novel
recombinants with possible increased pathogenic
potential.
• Designed and demonstrated the efficacy
against S. pyogenes infection of recombinant
vaccine candidate representing variants from
the conserved regions of the M protein. By this
design, the group have eliminated the need for
using extraneous sequences for maintaining the
conformation of the vaccine candidate.
• Showed that past infection with SIC-positive
group A streptococcus is a risk factor for chronic
kidney disease and that SIC seropositivity is
predictive of poor prognosis of CKD patients.
Bioinformatics
Team Head: Dr Lutz Krause
The Bioinformatics Team develops and applies bioinformatics methods in the context of biomedical research.
It specialises in biomarker discovery, infectious diseases and genetics and epigenetics of complex disorders.
The Team’s research focus is on investigating the role of the human microbiota in health and disease,
revealing the role of epigenetics in depression and the discovery of biomarkers for progression, personalised
treatment and prognosis of oesophageal adenocarcinoma.
CONDITIONS RESEARCHED
• Cancers
• Metabolic disorders
• Cystic fibrosis liver disease
• Obesity
• Depression
• Oesophageal cancer
• Diabetes
• Psychiatric disorders
• Endometriosis
• Schistosomiasis
• Inflammatory bowel diseases
• Streptococcal-related infections
CURRENT RESEARCH
• Comparative genomics of human parasites,
identification of vaccine and drug targets
• Discovery of biomarkers for prognosis,
progression and personalised treatment in cancer
• Epigenetics in complex disorders
• Role of the human microbiota and viruses in
health and disease
• Genome-wide association studies of genetic
disorders
• Development of methods for integrating, mining
and visualising heterogeneous datasets, including
genomic variations, gene expression and
epigenetic modifications
• Development of data-mining methods, machine
learning techniques and algorithms for the
analysis of microbial and viral metagenomes,
epigenetic samples, whole genome association
studies, next-generation sequence data
35
RECENT HIGHLIGHTS:
• Identified potential biomarkers for prognosis
and personalised treatment in oesophageal
adenocarcinoma.
• Published a genome-wide epigenetic association
study in the context of major depressive disorder.
• Started de novo sequencing of Schistosoma
bovis genome.
• Established several bioinformatics pipelines for
analysing next-generation sequencing data, which
are widely used for calling SNPs and analysing
RNAseq, MeDIP-seq and Chip-seq data.
• Identified mutations and rearrangements
important for cancer initiation and progression
using whole-genome and exome sequencing
of oesophageal adenocarcinoma samples in
collaboration with Princess Alexandra Hospital
and the Institute for Molecular Bioscience.
• Conducted a genome-wide epigenetic
association study in oesophageal
adenocarcinoma and Barrett’s oesophagus.
• Investigated the role of human microbiota in
various diseases and disorders including cystic
fibrosis, diabetes and parasite-bacteria coinfections.
Biomarkers and Biology of
Infection Related Cancers
Team Head: Dr Jason Mulvenna
RECENT HIGHLIGHTS:
• Characterised structure of TSP-2, a vaccine
antigen for schistosomiasis.
• Discovered potential miRNA markers for
nasopharyngeal carcinoma.
• Characterised proteomics of Necator americanus
for hookworm genome project.
Cellular Immunology
Group Leader: Associate Professor Scott Burrows
The Cellular Immunology Group focuses on the T cell immune response to viral infection, particularly EpsteinBarr virus which causes glandular fever and is associated with various malignancies and autoimmunity. The
molecular interactions that control the specificity of T cells recognition of virus-infected cells are complex and
could hold the key to preventing Epstein-Barr virus associated diseases.
CONDITIONS RESEARCHED
36
• Glandular fever
• Burkitt’s lymphoma
• Hodgkin’s lymphoma
• Nasopharyngeal carcinoma (nose and
throat cancer)
CURRENT RESEARCH
• Sequencing EBV genes from individuals in
different countries with different EBV-related
diseases helps to identify important EBV strains
• Helping to understand how our immune system
detects viruses in our body at the highest
possible resolution
RECENT HIGHLIGHTS:
• Showed that the dominant T cells of the immune
system remain stable throughout life.
• Showed that individual T cells of the immune
system are programmed to recognise peptides of
a particular size.
• Showed that very minor genetic differences
between people can have a major influence on
their immune response to pathogens.
Clinical Tropical Medicine
Senior Scientist: Professor James McCarthy
The Clinical Tropical Medicine Laboratory investigates how parasites such as the malaria parasite, hookworm,
threadworm and scabies cause disease and how they become resistant to drugs used to treat them. The
group also identifies new drugs and drug targets, and develops novel diagnostic techniques.
The focus of this laboratory is to apply modern techniques in microbiology, molecular biology and immunology
to study clinical problems associated with infectious diseases in tropical environments.
A particular interest in this laboratory is the study of drug resistance in a range of parasites, and the
development of novel diagnostic techniques.
CONDITIONS RESEARCHED
• Malaria
• Scabies
• Intestinal worms, including hookworm and
strongyloides
CURRENT RESEARCH
• Using experimental human malaria infection to
improve the understanding of the pathogenesis
of malaria and to develop new diagnostics, drugs
and vaccines.
• Improving the diagnosis and treatment of scabies
and intestinal helminth infections.
• Clinical trials of new drugs and vaccines for
infectious diseases.
RECENT HIGHLIGHTS:
• Defined the effectiveness of the experimental
antimalarial OZ439.
• Developed a system to undertake experimental
blood stage Plasmodium vivax malaria infections.
• Developed tests to measure the prevalence and
intensity of parasite infections in East Timor.
• Begun a Phase I study of a new vaccine for group
A streptococcus.
37
HIV Molecular Virology
Group Leader: Associate Professor David Harrich
The HIV Molecular Virology Group investigates fundamental mechanisms of virus replication with an overall
goal to identify key virus and host interactions required to support optimal virus replication. A main research
direction is analysis of a HIV-1 specific process called reverse transcription by which the viral RNA genome
is converted into DNA that can be inserted into human chromosomes, a permanent and irreversible event.
Using biochemical assays developed at QIMR Berghofer, the Molecular Virology Group identified human
proteins subverted by HIV to complete reverse transcription.
CONDITIONS RESEARCHED
• HIV/AIDS
• Hendra virus
• Respiratory syncytial virus (RSV)
CURRENT RESEARCH
• Analysis of HIV host dependency factors required
for early steps of HIV replication
• Analysis of cellular proteins regulating HIV Rev
protein function and trafficking in the cell
• Regulation of HIV replication by RNA and
ribonucleoprotein complexes
• Investigation of how cellular proteins facilitate
replication of RSV and Hendra virus.
• Development of potent antiviral proteins based on
the viral Tat protein
RECENT HIGHLIGHTS:
• Showed a novel protein inhibitor of HIV called
Nullbasic provided excellent protection from
infection in human cells in vitro.
• Discovered two unidentified host proteins
controlling the function of an important HIV-1
regulatory protein called Rev.
• Identified two cellular proteins that enable early
steps of HIV-1 infection.
• Challenged the role of a host protein called
PRMT6 as an HIV-1 restriction factors. A role for
PRTM6 in regulating a critical HIV-1 protein called
Tat, other than on increased protein stability,
remains unclear.
Human Immunity
Team Head: Dr John Miles
The Human Immunity Laboratory studies the immune processes which determine the host’s response to
infectious disease, cancer and innocuous agents. The team’s research focuses on T cells and their ligands,
exploring receptor genetics, biology, engagement and molecular structure across a number of human
disease systems. The team used information from these basic studies to modify T cell interactions and T cell
repertoires for use in rational vaccine design and therapeutic interventions.
38
CONDITIONS RESEARCHED
• Epstein-Barr virus (EBV)
• Burkitt’s lymphoma
• Nasopharyngeal carcinoma (NPC) (nose and
throat cancer)
• Hodgkin lymphoma
• Human cytomegalovirus (HCMV)
• Glandular fever
CURRENT RESEARCH
• Determining the biological relevance of T cell
receptor diversity in disease pathogenesis
• Determining the immunological consequences of
genetic diversity on pathogen defence
• Determining fundamental rules of engagement
between T cell receptors and their ligands
• Engineering affinity-enhanced T cell receptors and
ligands for new cancer therapeutics
RECENT HIGHLIGHTS:
• Deconstructed the proliferating neonate T cell
repertoire.
• Authored two reviews on manipulating the
immune system for therapeutic purposes.
• Led the first study to deep sequence the human
alpha/beta T cell repertoire over decades of life.
• Involved in studies revealing the basic
mechanisms behind human T cell function.
• Described the antigen recognition
compartmentalisation of the human T cell
repertoire.
Immunology and Infection
Group Leader: Dr Christian Engwerda
The Immunology and Infection Laboratory continues to try and understand why some immune responses
safely control parasite growth and protect against re-infection, whereas others cause disease during malaria
and leishmaniasis. The research has moved from a primary focus on studying immune regulation during
parasite infections in pre-clinical models of disease to validating our findings from these models using samples
from patients and volunteers deliberately infected with the parasites that the laboratory works on.
CONDITIONS RESEARCHED
• Malaria
• Visceral leishmaniasis (VL)
CURRENT RESEARCH
• Understanding how T cells behave during malaria
and leishmania.
• Investigating novel immune pathways activated
during malaria and leishmania.
• Identifying how T cells are regulated during
malaria and leishmania.
39
RECENT HIGHLIGHTS:
• Identified Blimp-1 as an important T cell
transcription factor for inducing immunoregulatory
IL-10 during malaria and leishmania.
• Showed that CTLA-4 blocks anti-malaria immune
responses.
• Discovered that a specialised T cell population
produces IL-17 very early during leishmania
infection and suppresses the ability of monocytes
to kill parasites.
• Identified new and critical roles for monocytes in
visceral leishmaniasis.
• Discovered that type I interferons suppress antiparasitic T cell responses in a pre-clinical model
of visceral leishmaniasis, as well as in clinical
samples from leishmania patients.
Inflammation Biology
Group Leader: Professor Andreas Suhrbier
The Inflammation Biology Laboratory is developing and exploiting knowledge about interactions between
viruses and the immune system to develop new anti-cancer, antiviral and anti-inflammation strategies.
CONDITIONS RESEARCHED
• HIV
• Pancreatic cancer
• Inflammatory diseases
• Skin cancers (including squamous cell carcinoma
and actinic keratosis)
• Mosquito-borne viruses (Ross River, chikungunya)
CURRENT RESEARCH
• Investigating the role of SerpinB2 (Plasminogen
Activator Inhibitor Type-2) during inflammation
and its potential role in regulating the adaptive
immune responses
• Investigating chikungunya virus and Ross
River virus disease – utilising mouse models to
understand how these virus causes arthritis.
Evidence suggests that the disease is caused
by the persistent productive infection of
macrophages in the joints and the release of proinflammatory mediators
• Investigating the mechanisms of action of Cpn10,
a proprietary drug being developed by Invion
limited as an immunomodulator for inflammatory
conditions such as rheumatoid arthritis and lupus
• Investigation the mechanisms of action of topical
ingenol mebutate / Picato a recently approved
drug for treatment of actinic keratoses (sun spots)
• Pancreatic cancer and Sin1
RECENT HIGHLIGHTS:
40
• Illustrated the utility of ingenol mebutate for fielddirected therapy of actinic keratoses to prevent
future development of skin cancers.
developed for rheumatoid arthritis may find utility
in the treatment of alphaviral diseases such as
Ross River virus and chikungunya disease.
• Uncovered the similarity in the inflammatory
disease seen in chikungunya virus and
rheumatoid arthritis, which suggests drugs being
• Showed that deficiency in interferon responses in
alphaviral infections is sufficient for haemorrhagic
fever and shock.
Malaria Immunology
Team Head: Dr Ashraful Haque
The Malaria Immunology Team use state of the art in vivo techniques to assess the immune response to
Plasmodium infection. The Team’s aim is to modulate the immune system to improve control of parasites.
CONDITIONS RESEARCHED
• Malaria
CURRENT RESEARCH
• Defining the role of type I interferon-associated
immune responses during Plasmodium infection.
• Discovering novel host genes that contribute
to pathogenesis during severe Plasmodium
infection.
RECENT HIGHLIGHTS:
sequestration in peripheral tissues drives large
increases in parasite biomass during severe
malaria.
• Demonstrated that CD8- dendritic cells are
suppressed via type I interferon signalling during
experimental malaria.
• Used mathematical and in vivo modelling
techniques to determine that parasite
• Demonstrated the role of IRF7 in suppressing T
cell immunity to Plasmodium.
Molecular Immunology
Team Head: Dr Michelle Wykes
The Molecular Immunology Team focuses on three areas:
• Identifying the role of PD-1 in malaria;
• Exploring their role of synthetically generated
immunological proteins as novel therapies for
malaria; and
• Investigating the kinetics of red cell clearance
during malaria.
CONDITIONS RESEARCHED
• Malaria
41
CURRENT RESEARCH
The major area of research interest is centred on understanding immunology of malaria and using this
knowledge to address fundamental questions in immunology. Research areas include:
• Identification of host molecular pathways
or immunological signals that contribute to
protection against malaria
• Using experimental rodent malaria infection to
understand the pathogenesis of malaria
• Identifying the role of dendritic cells in the life
cycle of the malaria parasite, Plasmodium spp.
• Development of novel efficacious long term
treatments for malaria.
RECENT HIGHLIGHTS:
• European Journal of Immunology commissioned
a commentary on the group’s publication showing
why antibody-based malaria vaccines may
not work.
Molecular Parasitology
Senior Scientist: Professor Don McManus
The Molecular Parasitology Laboratory researches the biology, pathogenesis and epidemiology of parasitic
worms that cause major clinical disease (schistosomiasis, echinococcosis (hydatid disease), soil transmitted
helminthiases), with the aim of developing new public health interventions, including vaccines, and diagnostic
procedures that will lead to their elimination through integrated control.
CONDITIONS RESEARCHED
• Schistosomiasis (Bilharzia)
• Hydatid disease
CURRENT RESEARCH
• Extensive human schistosome field studies in
Hunan Province (Dongting Lake region), Jiangxi
Province (Poyang Lake) and other provinces in
China.
• Characterising nuclear and mitochondrial
genomes and investigating molecular variation
both in the genomes and in key molecules that
may be the targets of new anti-schistosome and
anti-Echinococcus vaccines.
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• Dissecting the molecular and immunological
mechanisms involved in human disease caused
by schistosomes and Echinococcus.
• Identifying novel drugs and vaccine targets for
schistosomiasi.
• Development of new diagnosis methods for
hydatid diseas.
• Development of a vaccine against Echinococcus
for use in dog hosts.
RECENT HIGHLIGHTS:
• Determined the diagnostic value of non-invasive
biomarkers for stage-specific diagnosis of hepatic
fibrosis in patients with advanced schistosomiasis
japonica.
• Identified signalling pathways as putative targets
for control interventions against schistosomiasis.
• Completed a five year longitudinal study of
schistosomiasis transmission in an endemic area
in Schuan Province, China.
• Undertook an extensive proteomic
characterisation of Echinococcus granulosus
hydatid cyst fluid from sheep, cattle and humans.
• Defined a role for peroxisome proliferatoractivated receptors in the immunopathology of
schistosomiasis.
• Showed the value of schistosomiasis research in
the Dongting Lake region and its impact on local
and national control strategies in China.
• Defined the risk factors for helminth infections in
a rural and a peri-urban setting of the Dongting
Lake area, China.
• Completed a five-year longitudinal assessment
of the downstream impact on schistosomiasis
transmission in China following closure of the
Three Gorges Dam.
• Demonstrated that the insulin receptor is an
effective transmission blocking veterinary vaccine
target for zoonotic Schistosoma japonicum.
• Completed a cluster-randomised trial
demonstrating that a video-based health
education package prevents soil-transmitted
helminth infections in Chinese schoolchildren.
• Published a major article in the New England
Journal of Medicine describing the highly
successful outcome of a health education
package to prevent worm infections in Chinese
schoolchildren.
• Published a major review article in the New
England Journal of Medicine on chronic
enteropathogens in returning travellers.
• Published a major review on the structure and
function of invertebrate Kunitz serine protease
inhibitors.
• Completed a draft genomic sequence for
Echinococcus granulosus in collaboration with
Chinese colleagues.
Molecular Vaccinology
Group Leader: Professor Denise Doolan, Department Coordinator: Biology
The Molecular Vaccinology Laboratory’s research is focused on rational vaccine design, primarily for malaria,
and encompasses core themes of:
• Basic research on immune mechanisms and
adjuvant activity;
• Antigen and epitope discovery from genomic
sequence data using protein microarrays and
epitope prediction algorithms with biologically
relevant laboratory and field specimens; and
• Pre-clinical research and development of
antigen and epitope based molecular vaccine
technologies.
CONDITIONS RESEARCHED
• Malaria
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CURRENT RESEARCH
• Identifying and characterising target antigens and
epitopes for vaccine development
• Understanding mechanisms of protective
immunity and regulation of immunity
• Identifying novel adjuvants which enhance
vaccine-induced immunity, especially cell
mediated immune responses
• Evaluating novel vaccine delivery systems
RECENT HIGHLIGHTS:
• Identified four new malaria antigens as targets
of infection-blocking protective immunity against
malaria, and showed that antigen combinations
are more effective than individual antigens.
• Established that antigens that are highly reactive
for T cells are not dominant for antibodies
and are highly conserved; these data overturn
conventional dogma and suggest that new
strategies are required for T cell based vaccine
development.
• Produced protein microarrays for Plasmodium
vivax to identify excellent candidates for a malaria
vaccine or diagnostic test.
• Identified an adjuvant that activates dermal
dendritic cells, a specialised cell type shown to
be important for cross-presenting antigens and
activating CD8+ T cells.
• Developed a high throughput adjuvant screening
assay to identify novel adjuvants to enhance cell
mediated immunity.
• Showed that a natural product derived from
rainforests can protect against malaria, in a
mouse model.
• Evaluated a novel platform technology capable
of presenting multiple epitopes from a complex
pathogen in an authentic manner that maintains
the native antigenic structure.
• Evaluated the vaccine potential of a novel
bacterial platform shown to be effective for drug
delivery.
Mosquito Control
Group Leader: Greg Devine
Research in the Mosquito Control Laboratory focuses on the biology and control of mosquito-borne viruses
such as dengue, Ross River virus and Barmah Forest virus. This laboratory is designated by the World
Health Organization (WHO) as an official global Collaborating Centre for Environmental Management for
Vector Control.
The laboratory specialises in designing new mosquito surveillance and control strategies and has strong
collaborative linkages with dengue prevention research groups in Vietnam and Australia. Mosquito Control
researchers also work directly with State and local government in Queensland on mosquito control and all
mosquito-transmitted arboviruses.
HIGHLIGHTS:
• Wrote and edited a book on a world-first
eradication of the Australian southern saltmarsh
mosquito from New Zealand.
• Completed of a 5,000 household survey of
Brisbane to determine presence of exotic
mosquitoes.
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• Identified several proteins which can be used to
determine mosquito age.
• Conducted the first Wolbachia release for dengue
control in Vietnam.
Protein Discovery Centre
Group Leader: Professor Jeff Gorman
The QIMR Berghofer Protein Discovery Centre is a state-of-the-art facility recognised as a world leader in the
mass spectrometry and proteomics field and is one of the most advanced and best equipped of its kind in
Australia. The centre collaborates broadly on both national and international projects.
The centre aims to discover the identities of proteins involved in or affected by physiological and disease
processes and the ways in which these proteins function and interact and to develop techniques to observe
stimulated cells and the reaction within cell proteins.
CURRENT RESEARCH
• Viruses that cause serious respiratory diseases
of children
• Dioxin receptor – a xenobiotic regulator response
involved in cancer
• Signal-activated transcription factors involved in
cancer progression
• Cancer stem cell phenotype analysis – developing
markers for cancer stem cells
• Virally infected cells versus non-infected cells –
aimed at vaccine development
• Oxidative stress – in relation to virus infection and
mosquito age grading
• Hypoxia inducible factor which controls the
response to hypoxia – to determine if a particular
enzyme affects other proteins
RECENT HIGHLIGHTS:
• Characterised the proteomic component of A549
cells regulated by RSV infection and deduced
associated pathways.
• Developed a methodology for identifying specific
proteoforms from ambiguous protein group
database entries.
• Developed and deployed high-performance
proteomic approaches for analysing catalytic
properties and substrates of Kallikrein proteases
that putatively contribute to prostate cancer
progression.
• Developed and validated methods for production
of versatile probes of the calcitonin receptor.
• Characterised asparagine hydroxylation sites on
the TRPV3 protein.
• Developed advanced proteomic methodologies
to facilitate Rio Tinto Ride to Conquer Cancer
projects involving ephrin signalling and
cancer vaccines.
• Produced recombinant RSV-NS1 protein using
cell free and bacterial expression systems for
structural biology and protein-protein interaction
studies.
• Advanced the knowledge of protein expression in
the matrix of developing cartilage chondrocytes.
• Produced proteomic data to revolutionalise
annotation of the fungal pathogens of wheat.
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Tumour Immunology
Group Leader: Professor Rajiv Khanna
The major goal of the Tumour Immunology Laboratory is to obtain a deeper understanding of the mechanisms
by which an immune response to tumours may be generated, augmented and exploited for the treatment of
these cancers.
CONDITIONS RESEARCHED
• Epstein-Barr virus (EBV)
• Hodgkin’s lymphoma
• Nasopharyngeal carcinoma (NPC) (nose and
throat cancer)
• Human cytomegalovirus (HCMV)
CURRENT RESEARCH
• Design of recombinant therapeutic vaccines to
EBV-associated nasopharyngeal carcinoma and
Hodgkin’s lymphoma
• Developing a prophylactic vaccine for human
cytomegalovirus
• Targeting ubiquitously expressed EBV cancerassociated antigen EBNA1 for immunotherapy
RECENT HIGHLIGHTS:
• Completed Phase I clinical trial on adoptive
immunotherapy for stage IV nasopharyngeal
carcinoma (in collaboration with University of
Hong Kong).
• Developed novel T cell based therapy for the
treatment of brain cancer, glioblastoma.
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• Completed pre-clinical studies on the prophylactic
vaccine for human cytomegalovirus to prevent
birth defects.
• Completed clinical testing of a new diagnostic
test to predict cytomegalovirus-associated
complications in transplant patients.
MENTAL HEALTH/
COMPLEX DISORDERS
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Coordinator: Professor Michael Breakspear
QIMR Berghofer’s Mental Health/Complex Disorders Program combines a
number of disciplines to study the genetic and multi-factorial environmental
influences in a range of diseases from schizophrenia and depression to
haemochromatosis and migraine. These conditions hold an enormous
burden of illness and unmet research need.
QIMR Berghofer utilises imaging and gene sequencing technologies to
provide unprecedented insight into the biology of cells, animals and humans
and the genetic basis for a number of conditions.
Using brain imaging, computational modelling and epidemiological
studies, the Mental Health/Complex Disorders Program works to bring
public awareness and better understanding to mental illness and complex
disorders, while working to improve outcomes and recovery for those
suffering with these diseases.
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Asthma Genetics
Team Head: Dr Manuel Ferreira
The Asthma Genetics Team aims to identify genetic variants that influence the risk of developing asthma,
understand how genetic variants influence the risk of asthma and establish clinical trials to test new
treatments for asthma.
CONDITIONS RESEARCHED
• Asthma
CURRENT RESEARCH
• Analysis of whole-genome sequence data to
identify rare variants influencing the risk of asthma
• Characterisation of the asthma transcriptome
• Clinical trial of tocilizumab for asthma treatment
• Developing a new delivery method for
tocilizumab, so that it can be delivered directly to
the lungs
RECENT HIGHLIGHTS:
• Identified 10 loci influencing allergic sensitisation.
• Identified two new loci for asthma.
• Identified an additional regulatory variant in the
IL6R gene that associates with asthma risk.
Genetic Epidemiology
Senior Scientist: Professor Nick Martin
The Genetic Epidemiology Laboratory investigates the pattern of disease in families to assess the relative
importance of genes and environment in a variety of important health problems and to locate the genes
responsible using genome-wide association analysis.
CONDITIONS RESEARCHED
• Melanoma
• Anxiety, depression and fatigue
• Alcohol and nicotine dependence
• Osteoarthritis
• Mole development
• Asthma
• Iron absorption
• Endometriosis
• Super-fertility and twinning
• Migraine
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CURRENT RESEARCH
• Genetics of asthma
• Genetics of alcohol and nicotine dependence
• A twin study of mole development in adolescence
• A twin study of mental abilities and cognitive
performance
• A twin study of blood cell numbers
• Biology and molecular genetics of dizygotic
twinning
• The role of ADH and ALDH polymorphisms in
alcohol sensitivity in humans
• The role of HFE polymorphisms in iron
metabolism in Australian twins
• Genetic influences on endometriosis
• Asthma and allergy in Australian twins and their
families
• Osteoarthritis in ageing twins
• Psychosocial factors in cancer proneness in
ageing twins
• Genetic factors in anxiety, depression and fatigue
• Genetic analysis of migraine and comorbid
psychiatric disorders using twin families
RECENT HIGHLIGHTS:
• Played a leading role in the Enhancing
Neuroimaging Genetics through Meta-Analysis
(ENIGMA) consortium and identified the first
confirmed locus for a brain imaging phenotype,
for hippocampal volume on chromosome 12.
• Conducted the first full genome sequencing
project for a complex trait, which resulted in
finding a causal variant for melanoma in MITF.
• Discovered a new locus for melanoma on
chromosome one.
• Contributed to genome-wide association scan
(GWAS) meta-analysis, which found 65 new loci
for platelets with strong therapeutic potential.
• Contributed to GWAS meta-analysis, which
discovered six new loci for male pattern baldness
with overlap with prostate cancer and other
diseases.
• Contributed data that uncovering three new loci
for eczema.
• Contributed to discovery of a new susceptibility
locus near ODZ4 for bipolar disorder.
• Contributed to GWAS showing a tentative
association with depression on chromosome
three.
• Contributed to study finding new variants for
menopause and triple-negative breast cancer.
Hepatic Fibrosis
Group Leader: Professor Grant Ramm, Department Coordinator:
Cell and Molegular Biology
The Hepatic Fibrosis Laboratory investigates the cellular and molecular mechanisms of scar tissue formation
in the liver. This leads to fibrosis and cirrhosis in adult liver diseases, such as haemochromatosis and in
children, in diseases such as cystic fibrosis and biliary atresia.
The group is funded by the NHMRC to further investigate the role of hepatic stellate cells in human chronic
liver disease and the mechanisms associated with both their transformation into collagen-producing
myofibroblastic cells, as well as their role in wound healing in the regenerating liver following liver insult.
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CONDITIONS RESEARCHED
• Cystic fibrosis liver scarring
• Hepatitis C virus
• Biliary atresia
• Liver cancer
• Haemochromatosis
• Non-alcoholic fatty liver disease
CURRENT RESEARCH
• Role of hepatic stellate cells in fibrogenesis
associated with haemochromatosis
• Cellular and molecular mechanisms associated
with liver injury, wound healing, fibrogenesis and
tissue regeneration in chronic liver disease.
• Biomarker development for detecting, monitoring
progression and predicting clinical outcome of
chronic liver disease in children and adults
RECENT HIGHLIGHTS:
• Demonstrated a role for diabetes as a risk
factor for severe hepatic fibrosis in patients with
haemochromatosis.
Inflammatory Bowel Diseases Group
Group Leader: Dr Graham Radford-Smith
Inflammatory bowel diseases (IBD) are a group of diseases that affect the colon and small intestine, including
Crohn’s disease and ulcerative colitis. They affect up to one in every 200 Australians.
IBD is a medical condition that affects the gastrointestinal system, or gut. People with this illness often have
ongoing symptoms of tummy pain, diarrhoea, the passing of blood, and weight loss. They can also suffer
from other conditions that affect the skin, eyes and joints. Patients need medication for long periods of time
and many have bowel surgery. IBD affects both males and females, including children.
CONDITIONS RESEARCHED
• Inflammatory bowel diseases
• Ulcerative colitis
• Crohn’s disease
CURRENT RESEARCH
• Identification of genes associated with Crohn’s
disease and ulcerative colitis
• Incidence and prevalence of inflammatory bowel
disease in South-East Queensland
• The role of paneth cells in ileal Crohn’s Disease
• A research project looking into the causes of
inflammatory bowel disease
• Determination of disease-specific gene
expression signatures
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RECENT HIGHLIGHTS:
• Awarded grant for an ulcerative colitis GWAS.
• Carried out an immunochip study in collaboration
with the International IBD Genetics Consortium,
leading to a Nature publication.
• Consolidated a major collaboration with Amgen
(translational IBD research program).
• Analysed GWAS and immunochip data to identify
molecular signatures for IBD sub-phenotypes,
including acute severe colitis (and its response
to different therapies) and colorectal cancer
complicating colitis.
• Carried out parallel studies in colorectal cancer
cases complicating ulcerative colitis using exome
sequencing, to identify novel SNPs in this subgroup.
• Executed a GWAS in patients with refractory
ulcerative colitis.
• Completion of the first phase of the Crohn’s
disease PBS study – this has investigated
factors that significantly influence maintenance
of response to anti-TNF therapy across Australia
and New Zealand.
Iron Metabolism
Group Leader: Professor Greg Anderson, Deputy Director
The Iron Metabolism Laboratory focuses on understanding the homeostasis of the essential trace element
iron in the body and the natural history of disorders of iron metabolism, such as the iron loading disease
haemochromatosis. The laboratory’s work takes a broad approach from basic molecular mechanisms to
clinical applications.
CONDITIONS RESEARCHED
• Iron overload conditions (such as
haemochromatosis)
• Iron nutrition and supplementation during
pregnancy
• Iron homeostasis in neonates
• Iron loading anaemias (including thalassaemia
and haemolytic anaemias)
• Cystic fibrosis
CURRENT RESEARCH
• Mechanisms of intestinal iron absorption
• The role of iron oxidases in iron homeostasis
• Regulation of iron absorption and body iron
recycling
• Iron homeostasis in the perinatal period (in
pregnancy and newborns)
• The relationship between iron and Pseudomonas
infections in cystic fibrosis
• Population and clinical studies of
haemochromatosis
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RECENT HIGHLIGHTS:
• Showed a critical role for hephaestin and related
oxidases in iron absorption.
• Assessed the combined effects of multiple
hepatic toxins (iron, alcohol, fat) on liver disease
progression.
• Identified factors responsible for regulating
iron homeostasis in thalassaemia and other
haemolytic anaemias.
• Defined the effects of transfusion therapy on iron
and haematological parameters in patients with
beta thalassaemia.
• Identifed mutations in iron-related genes in the
Chinese population.
• Assessed the efficacy of nanoparticulate oral iron
supplements in rodent models.
Lung Inflammation and Infection
Team Head: Dr David Reid
The Lung Inflammation and Infection Team have focused on the role of iron in promoting bacterial infection
in the cystic fibrosis lung and whether this in turn is related to dysregulation of cell iron homeostasis in cystic
fibrosis. The team have spent the last year breeding the necessary mouse models and conducting preliminary
analyses of iron phenotype, while collecting samples from human subjects to conduct an epidemiological
study of gene mutations related to iron homeosatsis in CF patients. The team now has the required flow cell
bacterial biofilm models to allow testing of new therapeutic compounds.
CONDITIONS RESEARCHED
• Bronchiectasis
• Infectious diseases of the lung
• Cystic fibrosis
CURRENT RESEARCH
• Combine studies in humans, mice and
transfected cell lines to demonstrate that
abnormal iron homeostasis in CF promotes
bacterial infection with the pathogen
Pseudomonas aeruginosa and leads to worse
disease outcomes.
• Confirm the efficacy of interventions that target
bacterial iron homeostasis - particularly against
biofilm dwelling bacteria. These experiments
at present are targeting P. aeruginosa, but will
expand to antibiotic multi-resistant pathogens
such as MRSA and seek industry support as well
as generate an IP position.
• Study the microbiome of the normal human lung
and how this is affected by cigarrette smoking
and therapeutic interventions such as inhaled
54
corticosteroids. The team has spent 15 years
contributing to a very large biobank of human
lung tissues and have now completed analysis of
the lung microbiome in smokers with and without
COPD and will publish findings in 2013.
• Expand our biometal research into other chronic
respiratory diseases using a combination of
human and mouse studies with the goal of
investigating the role of metals, especially iron in
the development of COPD and lung malignancies;
lung cancer and mesothelioma.
RECENT HIGHLIGHTS:
• Developed a cystic fibrosis mouse model on a
new genetic background. This will allow novel
approaches to elucidation of the underlying
mechanisms of disease pathogenesis in this lethal
genetic disease.
• Developed methods to examine neutrophil
function in the lung and demonstration that the
oxidative burst potential of airway neutrophils from
CF patients is affected by airway environmental
conditions.
• Developed therapeutic approaches targeting
bacterial iron homeostasis, which appear very
active against bacterial biofilms.
• Commenced a new collaboration with a
bacteriophage company based in US.
Membrane Transport
Group Leader: Associate Professor Nathan Subramaniam
The major focus of the Membrane Transport Group is aimed at understanding how iron levels in the body are
regulated, the genes involved, their mechanism of action, and the role iron plays in various disorders including
liver disease and cancer.
CONDITIONS RESEARCHED
• Haemochromatosis (including juvenile
haemochromatosis)
• Atypical iron disorders
• Cancer-related proteins
• Anaemia
CURRENT RESEARCH
• Hereditary haemochromatosis caused by HFE
and non-HFE mutations
• Molecular, cellular and functional characterisation
of Transferrin Receptor 2
• Juvenile haemochromatosis
• Ferroportin disease or Type 4 haemochromatosis
clinical applications and population studies
RECENT HIGHLIGHTS:
• Showed that the presence of excess iron in
combination with a high calorie diet significantly
potentiates the progression of non-alcoholic fatty
liver disease, a relatively benign condition, to nonalcoholic steatohepatitis with fibrosis, a disorder
with significant associated morbidity and mortality.
• Demonstrated in mouse models of
haemochromatosis that, contrary to anecdotal
belief, iron accumulation in the liver does not
reflect iron loading of other organs, and is
therefore not a suitable surrogate for assessment
of disease potential in other organs in cases of
iron overload.
• Identified novel mutations in patients with atypical
iron overload through novel screening strategies.
• Developed and established novel and costeffective next-generation sequencing tools for
the rapid screening of genes involved in iron
metabolism.
• Demonstrated that in mouse studies treatment
with an antioxidant and a common spice can
reduce liver injury associated with excess iron and
a high calorie diet.
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Molecular Epidemiology
Group Leader: Professor Grant Montgomery, Department Coordinator: Genetics and
Computational Biology
The Molecular Epidemiology Laboratory seeks to identify genes and gene pathways contributing to risk
for common human diseases. The laboratory is a world leader in the genetics of endometriosis and works
on melanoma, inflammatory bowel disease and a range of other diseases including asthma, migraine,
depression, and alcohol, nicotine and drug dependence. The group maintains a large biobank supporting
projects in the laboratory and major collaborations with QIMR Berghofer’s Statistical Genetics, Genetic
Epidemiology, Oncogenomics, Asthma Genetics and Neurogenetics Laboratories.
CONDITIONS RESEARCHED
• Endometriosis
• Depression
• Melanoma
• Inflammatory bowel disease
• Alcohol, nicotine and drug dependence
• Twins and twinning
• Migraine
CURRENT RESEARCH
• Endometriosis
• Genetic Epidemiology studies
• Dizygotic twins
RECENT HIGHLIGHTS:
• Led significant advances in understanding
genes and pathways contributing to risk for
endometriosis by finding additional genomic
regions associated with risk, demonstrating
that the genetic factors underlying disease are
similar in European and Japanese populations,
and obtaining new funding to identify the specific
genes and pathways underlying increased
disease risk.
• Completed PhaseI genotyping for a genome-wide
association study (GWAS) in carefully selected
refractory and non-refractory cases to identify
specific genes that either alone or together
with key clinical variables will predict the risk of
developing medically refractory ulcerative colitis.
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• Discovered new genomic regions associated with
increased melanoma risk including discovery of
novel rare variants that predisposes to familial and
sporadic melanoma.
• Contributed to an international consortium
analysing the complex regulation of gene
expression and the role of genetic varaints
affecting complex disease.
Neurogenetics
Group Leader: Dr Dale Nyholt
The Neurogenetics Group’s focus is on the genetic analysis of migraine, endometriosis and traits comorbid
with migraine including depression and epilepsy. The primary goal of this research is to identify genetic
risk factors that lead to new knowledge of the underlying biological pathways contributing to disease
pathophysiology.
CONDITIONS RESEARCHED
• Depression
• Migraine
• Endometriosis
CURRENT RESEARCH
• Molecular genetic study of migraine
• Investigating link between endometriosis and
migraines
• Investigating links between migraine and
depression, anxiety, stroke, irritable bowel
syndrome, epilepsy and hypertension
• Identifying novel schizophrenia risk genes (1p31.1
and 1q23-25)
• Genome-wide association linking male patternbaldness and prostate cancer
RECENT HIGHLIGHTS:
• Reported six novel risk loci for androgenetic
alopecia and their association with Parkinson’s
disease and decreased fertility.
• Identified five new loci in a large endometriosis
meta-analysis.
• Reported five novel risk loci for migraine.
• Discovered four novel risk genes for migraine
without aura.
Neuroimaging Genetics
Group Leader: Dr Margie Wright
The Neuroimaging Genetics Group focuses on elucidating the neurobiological and genetic causes of major
mental illnesses through the integration of structural and functional neuroimaging, measures of cognition and
health and well being, and behavioural and molecular genetic approaches. The primary goal of this research is
the identification of the genes and pathways that influence the structure and function of the human brain, and
provide a window into the biological mechanisms leading to mental illness.
CONDITIONS RESEARCHED
• Depression
• Dementia
• Anxiety
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CURRENT RESEARCH
• Genetics of brain structure and function: The
QTIM (Queensland Twin IMaging) study
• Neurodevelopment during adolescence: a
longitudinal twin imaging study
• The Older Australian Twins Study (OATS)
of healthy brain ageing and age-related
neurocognitive disorders.
• Identifying genes for cognition.
• ENIGMA – Enhancing NeuroImaging Genetics
through Meta-Analysis
RECENT HIGHLIGHTS:
• Showed for the first time developmental changes
in structural connectivity and network efficiency.
• Identified genetic variants associated with bipolar
disorder.
• Provided evidence for a role of genetic factors in
several key brain metrics.
• Identified seven loci affecting mean telomere
length. The findings support a causal role of
telomere-length variation in some age-related
diseases.
• Identified associations between specific genes
and measures of brain structure and connectivity.
• Conducted the first GWAS meta-analysis of
childhood intelligence.
• Carried out GWAS met-analysis to identify
genetic variants associated with personality traits.
Variation in personality is predictive of many
outcomes in life, including mental health.
Quantitative Genetics
Team Head: Dr Sarah Medland
The Quantitative Genetics Team has focused on elucidating the biological pathways influencing common
psychiatric conditions including attention deficit hyperactivity disorder and substance use disorders.
CONDITIONS RESEARCHED
• Attention disorders
• Substance abuse
CURRENT RESEARCH
• Imaging and genetics
• Child and adolescent mental health issues
RECENT HIGHLIGHTS:
• Published work on the genetics of educational
attainment.
• Launched a new study on severe morning
sickness.
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• Biometrics
Statistical Genetics
Team Head: Associate Professor Stuart MacGregor
The Statistical Genetics Team studies the role that genetic variation plays in determining risk of disease and its
risk factors. The laboratory develops and applies statistical genetic methods to gene mapping studies across
a wide range of traits and diseases.
One major focus is understanding genetic and epigenetic variation in various cancers including melanoma,
ovarian cancer, and oesophageal cancer. Ultimately this work will lead to better understanding of why
particular individuals are affected by cancer or why they respond poorly to cancer treatment.
Another major interest is ophthalmological genetics, with work ongoing to identify the specific genes involved
in both eye disease and in underlying quantitative risk factors.
CONDITIONS RESEARCHED
• Breast cancer
• Melanoma
• Eye disease (myopia and glaucoma)
• Oesophageal cancer
• Endometriosis
• Ovarian cancer
CURRENT RESEARCH
• Statistical and computational methods in genetics
• Gene mapping studies in melanoma
• Epigenetic studies in ovarian and breast cancer
• Response to chemotherapy in ovarian cancer
• Genetic factors underlying esophageal cancer
and its risk factors
• Twin studies examining ophthalmogical traits
• Gene mapping studies on eye disease
RECENT HIGHLIGHTS:
• Identified a genetic variant in the obesity gene
FTO that confers risk of melanoma.
• Identified 24 new genetic variants conferring risk
of myopia.
• Identified 16 new genetic variants influencing
corneal thickness, several of which confer high
risk for the eye disease keratoconus.
• Found common genetic variants which
predispose Barrett’s oesophagus.
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System Neuroscience
Group Leader: Professor Michael Breakspear
Systems Neuroscience is an approach to brain sciences that seeks the fundamental principles of brain
organisation, dynamics and function across a hierarchy of spatial and temporal scales. It is a rapidly growing
field that differs considerably from the traditional reductionist paradigm in neuroscience that seeks purely
sufficient causes for local phenomena. In contrast, systems neuroscience seeks unifying explanations for
emergent phenomena.
CONDITIONS RESEARCHED
• Schizophrenia
• Dementia
• Depression
• Epilepsy
• Bipolar disorder
CURRENT RESEARCH
• Quantitative assessment of affect in major
depression
• Brain network mechanisms of resilience to
acquired cognitive impairment
• Psychosis and errors in perception during natural
vision.
• Fundamental mechanisms of perception and
motor control
• Cortical rhythms: The role of dynamics and noise
RECENT HIGHLIGHTS:
• Detected a biomarker for risk of bipolar disorder.
• Developed a new diagnostic test for cerebral
palsy.
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• Created an imaging test for major depression.
RESEARCH AND
TECHNOLOGY PLATFORMS
Our disease models and technologies are used globally
Oncology
• Compound screening for anti-tumour activity against a panel of human cancer
cell lines (cell growth and reporter gene assays)
• Mechanism of action of candidate anti-cancer drugs
• Mechanisms of gene regulation by agents, including use of microarray
technology
• Monoclonal antibodies for research and diagnosis
• Xenograft models
• Models investigating human cancer susceptibility
• EBV models
Cell and tissue
biology
• Confocal, electron, and laser dissection microscopy
• Signal transduction assays
• Histology and histopathology
• Cell sorting
• Fluorescence microscopy
Epidemiology
• QIMR Berghofer has access to extensive resources to facilitate nationwide
studies on important diseases. We combine classical epidemiological
methodology with genetic analysis of blood and tissue samples.
Genomics
• Mass array SNP typing facility
• Genome scans
• Zebra fish facility with many cutting edge methods for gene detection and
analysis
• Gene expression profiling of cancer cell lines and tumours
• cDNA library construction
• Information database on 30,000 twins and relatives
• DNA database of 5000 twins
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Infectious
disease
• Models for investigating the efficacy of vaccines or candidate drugs against
infectious disease, including malaria, leishmania, Group A streptococcus,
schistosomiasis and hook worms
• Viral protection assays
• Models for the effects of compounds on viruses including alphaviruses,
poxvirus (vaccinia) and herpes virus (cytomegalovirus)
• Models for evaluating drug resistance
Immunology
• Graft versus Host Disease transplantation models
• Models for evaluating anti-viral activity
• Effect of novel compounds, drugs, vaccines, immune-suppressants and
immune-stimulators on cytotoxic T lymphocytes
• In vitro and in vivo assays of activation of macrophages, NK cells, T cells, B
cells, Dendritic cells
• FACS analysis
• Multi-analyte system – multiplex for antibody and cytokine assays
Transgenic/
knockout mice
• Generation of knockout and transgenic mice
• Mouse embryo freezing
• Production of gene knockouts in specific tissues in mice
• Live animal imaging – detection of reporter gene expression
62
TISSUE BANKS
QIMR Berghofer has developed cancer tissue banks for
vital research
Samples
available
References
Tissue type
Background
Ovarian
cancer (1)
Blood, tissue and urine samples and
matching clinical data have been collected
from more than 1500 women with ovarian
cancer. Blood samples were also collected
from 1000 cancer-free control women
across Australia. Epidemiological data is
available.
Blood, urine
and tumour
tissue
Ovarian
cancer (2)
Blood samples have been collected from
200 women with ovarian cancer, 250 with
benign ovarian tumours
Blood and
tumour tissue
Breast cancer
A cohort study of multiple case breast
cancer families from whom extensive
genetic, clinical and epidemiological data is
available as well as biological specimens.
Collection is complete on more than 900
families.
Blood and
tissue samples
Kathleen Cunningham
Foundation
Consortium for
Research into Familial
Breast Cancer
Colon cancer
This bank contains over 800 fresh frozen
primary colorectal cancers. Collection
started in 1992 and is ongoing. There
are matched normal mucosa and blood
samples. Most samples have had DNA
extracted and paraffin fixed blocks and RNA
is available from selected samples.
Tissue from
primary tumours
Walter Paulsen Tumour
Bank
Melanoma and
skin cancer
Newly-diagnosed patients with melanoma
have been identified from the Queensland
Cancer Registry. Information is collected
on age, ethnicity, medical history and family
history of melanoma and skin cancer.
A brief sun exposure history has been
recorded, including details of residential
ambient solar exposure, as well as
occupational and recreational sun exposure
for each decade of life.
Paraffin sections
of tumour tissue
Australian Ovarian
Cancer Study
63
64
Samples
available
References
Tissue type
Background
Oesophageal
cancer
These samples are part of a national
population-based study of oesophageal
cancer. Blood and questionnaire data
is available for 1000 patients and 1500
cancer-free controls. Paraffin tissue blocks
are available for 800 patients.
Blood, tumour
tissue and
paraffin blocks
of tumour tissue
Australian Cancer
Study
Barrett’s
oesophagus
and reflux
conditions
Blood samples are available from 380
patients with Barrett’s oesophagus, 250
with gastro-oesophageal reflux disease and
700 controls
Blood samples
Study of Digestive
Health
YOUR PARTNER IN
- Clinical trial quality support
- Good manufacturing practice (GMP): Clean room hire;
GMP cell storage; Quality control testing
The QIMR Berghofer Medical Research Institute
(QIMR Berghofer) has been at the forefront of
medical research for the past 65 years.
• Quality control testing – sterility, Mycoplasma,
flow cytometry cell viability and identification
Initially established to meet the needs of
translational research within QIMR Berghofer,
Q-Gen has since gone on to have a strong track
record of clinical trials.
• Stock control
Q-Gen is licensed by the TGA (Licence No.
MI-11112004- LI-000153-1) for the maintenance
and storage of working cell banks, the storage
on site of cellular products. This licence makes
Q-Gen one of a very small number of organisations
in Australia able to store human samples under
GMP conditions.
The Q-Gen Facility Our GMP infrastructure,
including our TGA licensed quality system,
is designed to meet your clinical research
or start-up needs.
• ~1000m2 of dedicated floor space
• Clean rooms to meet ISO Class 7 and PC2
• Up to 13 rooms available, from 20m2 - 35m2
• Dedicated air handling units
• Swipe card access control on all rooms
THE Q-GEN SERVICE
We can offer a range of services backed by our
licensed quality system, risk based management
framework and project management policies.
A dedicated project manager is assigned to
every project to oversee all critical aspects of
your process.
• Records management
• Documentation development
• Leading clinical research, project management
and quality management advice
THE Q-GEN EQUIPMENT
Critical equipment is continuously connected to
an independent back-up power generator, with
24 hour monitoring of the equipment parameters
through our building management system. All
equipment is on a scheduled maintenance and
validation program to ensure high performance
standards are always met.
• Biological safety cabinets
• Incubators
• Centrifuges
• Liquid and vapour phase liquid nitrogen vessels
• -80°C to -20°C freezers
• Stability fridges
• Access to a wide range of general and
specialised research equipment
Please direct enquires to:
Darron Laing
Q-Gen Facility Manager
T +61 7 3845 3851
E [email protected]
300 Herston Road, Herston, Qld 4006
• Research through to GMP storage of human and
non-human cells and cellular products
• Storage temperature range of -190°C through to
ambient
65
300 Herston Road
Herston QLD 4006 Australia
Locked Bag 2000
RBH QLD 4029 Australia
T +61 7 3362 0222
1800 993 000
F +61 7 3362 0102
[email protected]
Better health through medical research | www.qimrberghofer.edu.au