Proteomics

Dr Daniel Garama is the Head of Proteomics at Hudson Institute of Medical Research. He has dedicated his career to the use of protein chemistry and proteomic approaches to elucidate and understand fundamental biological mechanisms that lead to clinical and commercial outcomes. He specialises in proteomic techniques, particularly the design and use of mass spectrometry to identify protein interactions, function and post translational modifications. Dr Garama has over 15 years of experience in this field, and has undertaken training at specialist international facilities to become an expert in both qualitative and quantitative techniques, along with specialist training in native-MS, hydrogen-deuterium exchange-MS, label free-MS, lipidomic and post translational modification analysis.

His current research interest surrounds mitochondrial proteomics, particularly those involved in mitochondrial biogenesis and the import, modification and interactions of non-MTS tagged proteins into the mitochondria. Dr Garama is an affiliate member and adviser at the Bio21 Mass Spectrometry and Proteomics Facility (MSPF), Melbourne University and also at Monash University.

Endocrine Hypertension Service

Dr Jun Yang taking patient David Dents blood pressure test
Dr Jun Yang with patient David Dent

The Endocrine Hypertension Service was established in July 2017 and operates on Thursday mornings and alternate Wednesday mornings in the Department of Endocrinology, on Level 3, Block E, Monash Medical Centre.

This clinic has been established to facilitate the diagnosis and management of endocrine causes of hypertension, with a particular focus on primary aldosteronism.

We have the capacity to review patients frequently for medication adjustments and blood pressure monitoring during the diagnostic process.

For patients who are found to have aldosterone producing adenomas, we can facilitate medical stabilisation prior to surgery.

Referrals can be faxed to Ms Elise Forbes (dedicated clinic nurse) on (03) 9594-3558

Primary Aldosteronism Centre of Excellence (PACE)

The Primary Aldosteronism Centre of Excellence (PACE) is an inter-disciplinary and trans-national collaboration established in December 2018 to build capacity in the field of primary aldosteronism (PA) research in Australia and address knowledge gaps using a systematic and evidence-based approach.

PACE is built on existing collaborations and led by internationally respected clinician-scientists in PA-related research in Australia, including Professor Peter Fuller from Hudson Institute of Medical Research/Monash Health, Professor Michael Stowasser and Dr Martin Wolley from Queensland University, who have published extensively in the field and set the standards for PA management in Australia. PACE also has the support of world leaders in cardiovascular endocrinology, resistant hypertension research and cardiovascular epidemiology, A/Professor Morag Young (Baker Institute), Professor Markus Schlaich (University of Western Australia), Professor Trevor Mori (University of Western Australia) and Professor Christopher Reid (Curtin University); primary care health services researcher, Professor Grant Russell (Monash University); health economist, A/Professor Gang Chen; and senior biostatistician, Dr StellaMay Gwini (Monash University/Barwon Health).

Our goals

  • Optimise the timely and accurate diagnosis of PA through high quality, collaborative research and transformation of clinical practice guidelines and diagnostic methods;
  • identify genetic and environmental factors, as well as novel biomarkers, that will underpin personalized diagnostic tests and therapeutics in the prevention and management of PA; and
  • create translational research environments and develop clinical trial platforms to build the capacity for world-leading PA research by Australian clinicians and scientists.

BRCA1 and BRCA2 focused breast and ovarian cancer research

BRCA1 and BRCA2 focused breast and ovarian cancer research

About the BRCA1 and BRCA2 mutation

Breast cancer is the most common cancer affecting women in Australia with 134,000 new cases diagnosed each year. On average, 37 women are diagnosed with the disease every day.  Around 12 per cent of women will develop breast cancer in their lifetime.

Ovarian cancer is the second most commonly diagnosed gynaecological cancer. The majority of the 1,500 Australian women diagnosed with ovarian cancer each year are diagnosed with advanced stage disease. On average, four Australian women are diagnosed with ovarian cancer every day.

The BRCA1 and BRCA2 genes are key tumour suppressor genes that are normally expressed in breast or ovarian tissue, where they work to repair DNA damage and prevent tumours from forming. In women with a mutation in the BRCA1 gene, this DNA damage cannot be repaired, meaning they are at a much greater risk of developing breast and ovarian cancer.

Women with a mutation in the BRCA1 gene are at a higher lifetime risk of developing breast cancer (30 – 65 per cent) and ovarian cancer (20 per cent), often at an early age. While regular screening can detect breast cancer at an early stage and survival rates for breast cancer have improved, there is still a pressing need to develop effective preventative strategies for women who are at a high risk of inherited disease.

Critically, for a fifth of women with BRCA1 or BRCA2 mutations, genetic based tests cannot currently predict if they will develop breast cancer. The mutations for this group are too rare and it is still unknown whether these mutations impact tumour development. Understanding the impact of these mutations may prevent unnecessary surgical intervention.

Research is the way to help. Better understanding of how tumours originate, grow and spread results in better ways to prevent, detect and treat breast and ovarian cancer in women with a BRCA1 mutation.

 

Our BRCA1 and BRCA2 cancer research focuses on

  • Understanding how the female hormone oestrogen contributes to BRCA1-associated breast cancer
  • How blocking the cancer-promoting effects of oestrogen could provide an alternative to mastectomy in high-risk women with a BRCA1 mutation
  • A novel screening test for ovarian cancer in women with BRCA1 and BRCA2 mutations
  • The development of new ways to characterise the impact of rare BRCA1 mutations on tumour development.

 

Key areas of investigation

1. Oestrogen metabolism and BRCA1-associated breast cancer

Women who harbour a mutation in BRCA1 have an increased risk of developing breast cancer. BRCA1 normally repairs damaged DNA but when mutated, BRCA1 loses this activity – increasing the chances that naturally-occurring DNA damage goes unrepaired, leading to cancer.

BRCA1 is present throughout the body but it is unclear why cancers related to it are largely confined to the breast. The female hormone oestrogen is thought to be involved, since breast tissue is highly sensitive to this hormone. However, once established, most BRCA1-associated breast cancers are oestrogen-independent.

Oestrogen can be converted to other compounds in the breast. Some of these compounds attach to DNA and cause damage. With no BRCA1 activity to repair this damage, this may be one reason why BRCA1 cancers are most common in the breast.

We are seeking to discover if blocking the production of these toxic oestrogen metabolites can protect against breast cancer development when BRCA1 is mutated. We are also using the Human Variome Project to determine if natural variation in genes involved in oestrogen metabolism contributes to breast cancer risk in BRCA1 mutation carriers.

Understanding pathways of oestrogen metabolism may lead to new BRCA1 prevention strategies, as an alternative to mastectomy.


Cancer Drug Discovery

Collaborations

Florey Institute, Melbourne
St Vincent’s Institute, Melbourne
Duke University, USA

Supporters

NHMRC
Cancer Council VIC

 

2. Early detection test – reducing the need for surgery

Women with hereditary mutations in the BRCA1 or BRCA2 genes have an elevated risk of developing ovarian cancers. Prophylactic surgery to remove the ovaries and fallopian tubes (salpingo-oophorectomy) can reduce the risk of developing ovarian cancer by up to eighty per cent. As a result, many women elect to have surgery as a risk-reducing strategy. However, the majority of these women do not have any evidence of cancer and surgically induced menopause increases their risk of other diseases, including osteoporosis and cardiovascular disease. A method to determine the need for surgery in this group of ‘at risk’ women is required.

We are trialling a new diagnostic test for the detection of early-stage ovarian cancers in women carrying hereditary mutations in the BRCA1 or BRCA2 genes. Unlike genetic testing, which indicates only a predisposition to develop cancer, this new test identifies biological changes associated with the early stages of cancer formation. By using this test to detect early-stage cancers, the majority of women could be spared the risks of surgery and its associated side-effects.

Our goal is to establish this test in a regular screening program. Successful implementation will greatly decrease the number of women undergoing surgical intervention, allowing the majority to lead full, healthy lives.


Ovarian Cancer Biomarkers

Collaborations

Monash Medical Centre, Melbourne
Royal Adelaide Hospital, Adelaide

Supporters

The Ovarian Cancer Research Foundation

 

3.  microRNAs – the secret weapon in BRCA1 detection

Global efforts are currently carried out through initiatives such as the Human Variome Project to increase the power of the correlations between rare BRCA mutations and cancer occurrence – but these approaches are mainly based on the more common BRCA1 or BRCA2 mutations.

microRNAs are small regulators of gene expression that play critical roles in multiple diseases including cancer and are secreted in most biofluids such as blood serum, urine and saliva. Our laboratory has discovered that molecular variations exist within microRNAs, which when analysed markedly increase their accuracy in disease prognosis.

BRCA1 directly controls the levels of select microRNAs. As such, microRNA levels can be used to identify mutations, severely impacting the function of BRCA1, even when extremely rare.

In the current project, we are analysing the impact of BRCA1 mutations on molecular variations of these microRNAs in breast cancer samples from The Cancer Genome Atlas, with the aim of defining novel biomarkers linking uncharacterised BRCA1 mutations with breast cancer development and progression.


Nucleic Acids and Innate Immunity

Collaborations

Sanger Institute, UK
University of South Australia, Adelaide

Supporters

ARC (Future Fellowship)

 

Hudson Monash Paediatric Precision Medicine Program

The Hudson Monash Paediatric Precision Medicine (HMPPM) Program hopes to significantly improve treatment for childhood cancer patients with the greatest unmet clinical need – those diagnosed with brain cancers and solid tumours. The program was established in 2017 with investment from the Children’s Cancer Foundation.

Hudson Monash Paediatric Precision Medicine Program team
Hudson Monash Paediatric Precision Medicine Program team

In a collaborative program, scientists at Hudson Institute of Medical Research have established a living biobank of paediatric brain tumours and solid cancers, to trial and develop targeted treatments and improve clinical outcomes, survival rates and quality of life (limiting side-effects) for childhood cancer patients.

Innovation in the making  

The HMPPM Program marks a significant investment in future clinical management and novel research discovery in childhood cancer. The program includes:

The development of a living tumour biobank for paediatric solid tumours

At present, very few reliable patient-derived preclinical models are available to researchers. To bridge this gap, our program establishes and banks cell lines, 2D and 3D xenograft models directly from childhood tumour tissue. The establishment of a living biobank for paediatric solid tumours provides a critical renewable resource for local, national and international researchers.

The establishment of a functional genomics pipeline

We capitalise on the living biobank tumour samples to integrate genomic data (next generation sequencing) with functional data obtained from high-throughput genetic screening (Cas9/CRISPR) and results from global pharmacological drug screens.

Multi-dimensional analyses of paediatric cancers

We will comprehensively profile paediatric cancers (both tissue and matched model) in 4 dimensions (genomic, epigenomic, transcriptomic, and proteomic) to provide both gene-specific and pathway level analyses of paediatric tumours. This work enables both a richer biological understanding of paediatric cancers and facilitates the utilisation of diverse molecular variables in cancer precision medicine.

Translation of genomic data into targeted therapy

The comprehensive molecular analysis of individual patient tumours will help identify both new and existing therapies that can be rapidly implemented in the clinic. This approach will facilitate clinical implications of data from the functional genomics pipeline for individual paediatric patients.

Molecular Tumour Board (MTB): integrating findings into clinical management

Working in collaboration with the Zero Childhood Cancer (ZCC) and PRISM program (zerochildhoodcancer.org.au), the paediatric cancer molecular MTB will integrate molecular and functional diagnostic assays into clinical management of childhood cancer patients, by providing expertise and recommendations on the clinical implications of findings that arise from molecular analyses.

Unique national and global collaborations

The establishment of a living biobank and functional genomic testing for paediatric solid tumours provides a critical resource for local, national and international researchers. Thus, a key element of the program includes national and international stakeholders’ involvement to build expertise, share resources and disseminate results that will advance the field of precision medicine for paediatric cancer patients. For more information, see the Affiliations and Partners section below.

Progress to Date

To date, we have collected tissue samples from 223 patients (including collaborator sites) and successfully established 3-dimensional cell cultures (‘organoids’) of paediatric solid tumours as well as 2-dimensional cell cultures. We have conducted over 200 high-throughput drug screens and identified a number of promising therapeutic targets for paediatric brain cancers and sarcomas.

Our scientific team has streamlined the process of drug screening (within a few weeks post sample collection), data generation and integrative analysis to efficiently identify cancer dependencies for individual patients; and have devised a functional genomics pipeline that generates CRISPR loss of function sensitivity data for patient-derived cell lines.

Other research directed at molecular and cell pathways, with investigation into pharmacogenomics, diversity of cancer genetics, pluripotent stem cells is underway, and offers excellent opportunities for young researchers.

Members

Program leadership

A/Prof Ron Firestein | Head of Research and Chief Investigator
Dr Jason Cain | Chief Investigator
Dr Daniel Gough | Chief Investigator
Prof Annie Huang | Chief Investigator
Dr Peter Downie | Head of Clinical Enterprise
Naama Neeman | Children’s Cancer Foundation Administrative Director
Prof Bryan Williams | Strategic Advisor

Research team

Dr Paul Daniel | Children’s Cancer Foundation Postdoctoral Research Fellow
Caroline Drinkwater | Australian Lions Childhood Cancer Research Foundation Senior Biobank Specialist
Rajithri (Dilru) Habarakada | Australian Lions Childhood Cancer Research Foundation Senior Biobank Specialist (maternity leave appointment)
Dr Claire Sun | Children’s Cancer Foundation Bioinformatician
Nicole Chew | Children’s Cancer Foundation Senior Organoid Specialist
Dr Nataliya Zhukova | My Room Clinical Research Fellow
Dr Paul Wood | Paediatric Oncologist
Dr Gabrielle Bradshaw | Alfie Chivers Research Fellow – funded by Robert Connor Dawes Foundation
Melissa Loi | Children’s Cancer Foundation Technical Sequencing Specialist
Hui (Claire) Shi | Children’s Cancer Foundation PhD Student
Sarah Parackal | Children’s Cancer Foundation PhD Student
Dasun Fernando | PhD Student
Motahhareh (Flora) Tourchi | PhD Student
Jay Yang | Masters Student
Mia Pörksen | Internship
Prof Roger Daly | Molecular analysis group (proteomics)
Prof Roger Reddel | Molecular analysis group (proteomics)

Administrative support

Janelle Cooke | Molecular Tumour Board Project Manager – maternity leave
Ma’ayan Geffen | Molecular Tumour Board Project Manager
Steph Forman | Personal Assistant to A/Prof Ron Firestein

Affiliations and partners

Zero Childhood Cancer (Children’s Cancer Institute)
Australian & New Zealand Children’s Haematology/Oncology Group (ANZCHOG)
Monash University
Monash Health
Monash Children’s Hospital
The Royal Children’s Hospital
Murdoch Children’s Research Institute
Queensland Institute of Medical Research Berghofer

International partnerships

Children’s Brain Tumor Tissue Consortium (CBTTC)
Hospital for Sick Children (SickKids)
Children’s Hospital of Philadelphia
University of Santa Cruz
Hubrecht Institute
KK Women’s and Children’s Hospital, VIVA Foundation for Children with Cancer
German Cancer Research Centre (DKFZ)
Beijing Genomic Institute (BGI)

Funding sources   

The Hudson Monash Paediatric Precision Medicine Program is made possible thanks to generous and exclusive funding from the Children’s Cancer Foundation.

Funder Children's Cancer Foundation

We are also thankful for the support of the Australian Lions Childhood Cancer Research Foundation (ALCCRF) and the Robert Connor Dawes (RCD) Foundation.

Funders ALCCRF

Contact

Naama Neeman
Children’s Cancer Foundation Administrative Director
Hudson Monash Paediatric Precision Medicine Program
e: naama.neeman@hudson.org.au

Paediatric Cancer Research Program

The Paediatric Cancer Research Program is a collaborative Melbourne-based initiative

Bringing together researchers and clinicians across Hudson Institute of Medical Research, Monash Children’s Hospital, Monash Children’s Cancer Centre and Monash University.

Together, our common objective is to improve outcomes in children diagnosed with cancer through innovative research into the development and progression of these diseases and identification of new and more effective therapeutic strategies.

In 2015 in Victoria alone, 156 children under the age of 14 years old and 246 adolescents and young adults between the ages of 15-24 years old were diagnosed with cancer*. Despite a >80% survival rate, many patients will suffer permanent side effects of their disease and/or treatments. The predicted increase in new cancer diagnoses (53%) and deaths (25%) in Victoria over the next 10-15 years* highlights the urgent need for researchers and clinicians to join forces to improve understanding of paediatric cancers and translate these findings into the clinic.

*Cancer Council Victoria.

The Paediatric Cancer Research Program aims to significantly contribute to the understanding of all childhood cancer. The expanding profile of research interests currently include:

‒ Atypical Teratoid Rhabdoid Tumour (AT/RT)
‒ Diffuse Intrinsic Pontine Glioma (DIPG)
‒ Ependymoma
‒ Leukaemia
‒ Malignant Rhabdoid Tumour (MRT)
‒ Medulloblastoma
‒ Neuroblastoma
‒ Sarcoma’s (including Osteosarcoma)
‒ Wilm’s tumour
‒ Paediatric Cancer Precision Medicine
‒ Paediatric Cancer Tissue Banking and Model Development
‒ Molecular Profiling of Brain and CNS Malignancies

For more information on our research, please click on the member links below.

Members

Dr Beena Kumar (Principal investigator Monash Surgical Oncology Biobank/ Monash Children’s Cancer Biobank)
Prof Bryan Williams (Emeritus Director and Distinguished Scientist, Hudson Institute; Research Group Head, Cancer and Innate Immunity; Program Director, Hudson Monash Paediatric Precision Medicine Program)
Dr Paul Wood (Group Leader, Paediatric Oncologist; Associate Investigator, Hudson Monash Paediatric Precision Medicine Program)
Caroline Drinkwater (Children’s Cancer Foundation Biobank Specialist, Hudson Monash Paediatric Precision Medicine Program)
Dr Christine White (Postdoctoral Research Fellow, Genetics and Molecular Pathology)Affiliations & Partners
Claire Shi (Children’s Cancer Foundation PhD Student, Hudson Monash Paediatric Precision Medicine Program)
Dr Daniel Gough (Research Group Head, STAT Signalling Laboratory; Principal Investigator, Hudson Monash Paediatric Precision Medicine Program)
Dasun Fernando (PhD student, Cancer and Innate Immunity)
Dr Duncan Crombie (Children’s Cancer Foundation Senior Organoid Specialist, Hudson Monash Paediatric Precision Medicine Program)
A/Prof Elizabeth Algar (Research Group Head, Genetics and Molecular Pathology; Chief Investigator, Hudson Monash Paediatric Precision Medicine Program)
Enola Roussel (Honours student, Developmental and Cancer Biology)
Dr Jason Cain (Research Group Head, Developmental and Cancer Biology; Chief Investigator, Hudson Monash Paediatric Precision Medicine Program)
Naama Neeman (Children’s Cancer Foundation Head of Operations, Hudson Monash Paediatric Precision Medicine Program)
Nataliya Zhukova/ (My Room Clinical Research Fellow, Hudson Monash Paediatric Precision Medicine Program/Developmental and Cancer Biology)
Dr Paul Wood (Group Leader, Paediatric Oncologist; Associate Investigator, Hudson Monash Paediatric Precision Medicine Program)
Dr Peter Downie (Head, Monash Children’s Cancer Centre; Head of Clinical Enterprise and Chief Investigator, Hudson Monash Paediatric Precision Medicine Program)
A/Prof Ron Firestein (Centre Head, Centre for Cancer Research; Research Group Head, Cancer Genetics and Functional Genomics; Head of Research and Chief Investigator, Hudson Monash Paediatric Precision Medicine Program)
Dr Samantha Jayasekara (Research Assistant)
Sarah Parackal (Children’s Cancer Foundation PhD Student, Hudson Monash Paediatric Precision Medicine Program/Developmental and Cancer Biology)
Dr Sara Khan (Australian Lions Childhood Cancer Research Foundation Fellow)
Dr Vijesh Vaghjiani (Postdoctoral Research Fellow, Developmental and Cancer Biology)
Wai Chin Chong (PhD student, Developmental and Cancer Biology)
Zdenka Prodanovic (Principal Advisor, Monash Children’s Cancer Biobank)

Affiliations and Partners

Centre for Cancer Research, Hudson Institute of Medical Research
Monash Children’s Hospital
Monash Children’s Cancer Centre, Monash Health
Genetics and Molecular Pathology, Monash Health
Monash Children’s Cancer Biobank, Monash Health
Monash University

Funding Sources

National Health & Medical Research Council
Monash Comprehensive Cancer Consortium
Australian Lions Childhood Cancer Research Foundation
Australasian Sarcoma Study Group
Bailey’s Day
Children’s Cancer Foundation
The Robert Connor Dawes Foundation (RCD Foundation)
The Cure Starts Now: Australia
Isabella and Marcus Foundation
Victoria Cancer Agency

In the news

Herald Sun: ‘A fight for the kids,’ 4 October 2014
Herald Sun: ‘Cancer battle can’t conquer little Zac,’ 18 October 2014
ALCCRF Newsletter: ‘ALCCRF Fellowship,’ August 2015
Herald Sun: ‘Children with common brain tumour to have routine analysis under national service,’ 27 September 2016
Ten Eyewitness NEWS: ‘Cancer Fight,’ 27 September 2016
7 NEWS: 27 September 2016
Hudson News (summer edition): ‘Australian first – crucial service to help children with brain tumours,’ 3 November 2016
ALCCRF Newsletter: ‘Appointment of ALCCRF Clinical Research Fellow at Monash
Children’s Hospital and Hudson Institute of Medical Research,’ June 2016