Cancer
See CANCER - Fertility Preservation
Examination of circulating pre-treatment biomarkers of patient response to bone marrow transplantation
Supervisors: Rachel Koldej, Joanne Davis, Eric Wong
Project Site: ACRF Translational Research Laboratory, Victorian Comprehensive Cancer Centre
Contact: Rachel Koldej E: rachel.koldej@mh.org.au
Project description: The Royal Melbourne Hospital (RMH) is one of the largest providers of allogeneic haematopoietic cell transplantation (alloHCT) in Australia. AlloHCT is a complex but potentially curative procedure for patients with haematologic malignancies or bone marrow failure syndromes. The fundamental principle of alloHCT is that a donor’s haematopoietic stem cells (or graft), when infused into the recipient, will develop into a new set of immunologically active cells that recognise tumour cells as foreign and contain or destroy them. Retrospective studies in alloHCT have been pivotal in unlocking key pieces of knowledge that have shaped and continue to shape transplant clinical practice.
The RMH Bone Marrow Transplant Service already possesses a comprehensive, HREC-approved clinical databank which contains detailed pre- and post-transplant data including crucial outcome measures and the ACRF Translational Research Laboratory (located at the Victorian Comprehensive Cancer Centre) has HREC-approved access to an existing set of archival post-transplant patient samples. We are now examining these samples for markers that predict pre-treatment how a patient will respond to alloHCT. This would allow the patients treatment to be modified to prevent adverse outcomes including acute or chronic graft-versus-host disease. Markers currently under evaluation include circulating microRNAs, cytokine levels and the presence of single nucleotide polymorphisms in either the transplant donor or recipient. The potential biomarkers to be examined in this project include the chemokine CXCL10 (Ahmed et al, 2015, Bone Marrow Transplantation) and soluble DNAM-1 (Kanaya et al, 2016, PLOS One).
This project combines both laboratory and clinical correlative research and has HREC approval. All samples and clinical data required for the successful completion of the project are available.
Psychosocial and behaviioural outcomes of women at high pedigree based risk of breast and/or ovarian cancer
Supervisors: Dr Lesley Stafford, Prof Bruce Mann, Prof Geoff Lindemann
Project Site: Centre for Women’s Mental Health, Royal Women’s Hospital
Contact: Dr Lesley Stafford. E: Lesley.Stafford@thewomens.org.au T: 61 03 8345 3909
Project description: Data has been collected from 372 women (193 affected by cancer and 178 unaffected by cancer) at high pedigree based risk for breast and/or ovarian cancer who have either had genetic testing for a deleterious gene mutation (BRCA 1 or BRCA 2) with an uninformative result, or who cannot be personally tested for a range of reasons.
It is not well understood how these women perceive their risk of cancer, manage their disease risk or adjust psychologically in the context of a lack of established risk management guidelines.
The cross-sectional data collected relate to risk management practices for breast/ovarian cancer including screening, surgery and lifestyle modification; and psychological morbidity in the form of depression, anxiety, cancer-specific distress and worry. Other psychological data collected include levels of neuroticism and cognitive representations of illness.
Glioma stem cells: biology and molecular targets
Supervisor: Dr Andrew Morokoff
Co-Supervisors: A/Prof Kate Drummnod, Prof Andrew Kaye.
Location: Department of Surgery, Royal Melbourne Hospital
Contact: Dr Andrew Morokoff (morokoff@unimelb.edu.au) T: 9035 8586
Project Description: Giomas are common malignant brain tumours with an extremely poor survival because of their highly invasive nature and high recurrence rate. Recently a subpopulation of cells with stem-cell like properties has been identified in gliomas and these cells are thought to be related to recurrence and treatment resistance. Furthermore, certain molecular pathways that lead to invasion, apoptosis and drug resistance effects may be ‘switched on’ specifically in glioma stem cells. This project involves establishing stem cell cultures directly from surgical brain tumour samples and isolating cancer stem cells in neurspher cultures in vitro. These cell lines will be assessed for alterations of molecular signalling pathways including be new techniques such as next-generation whole genome and transciptome sequencing. These celll lines and mouse xenograft models utilising bioluminescence will be used to test novel compounds targeting these pathways.
Twist as a Regulator of EMT in Gastric Cancer and its role in invasion
Supervisors: A/Professor Alex Boussioutas. Co-supervisor: Dr Rita Busuttil
Project Site: Peter MacCallum Cancer Centre
Contact: A/Professor Alex Boussioutas T: +61 03 9656 1287 E: alexb@unimelb.edu.au or alex.boussioutas@petermac.org; Dr Rita Busuttil T: +61 03 9656 1287
E: Rita.Busuttil@petermac.org
Gastric cancer (GC) is often diagnosed at advanced stages, giving patients a 5-year survival of less than 20%. Advanced stage GC is directly correlated with increased local invasion of the cancer through the gastric wall and, at more advanced stages into adjacent structures.
Epithelial Mesenchymal Transition (EMT) is one mechanism which has been proposed as a modulator of invasion in GC as well as other cancer types. This project seeks to expand on previous work in our laboratory exploring the role of TWIST, a master regulator of EMT, in gastric cancer. We have previously shown that TWIST is more highly expressed at the invasive front of the tumor compared to its core indicating that EMT is occurring in this area. It is conceivable that reducing TWIST expression could be used as a means to decrease the invasive capacity of a cancer.
This project will aim to further explore the role of TWIST in the invasion of GC and its potential utility as a therapeutic target. A broad range of techniques including bioinformatics, cell culture, shRNA lentivirus mediated gene knockdown, and molecular biology will be applied.
We are looking for motivated students (both Honours and PhD students) to strengthen our group.
Validation of candidate genes involved in the progressionof gastric cancer
Supervisors: A/Professor Alex Boussioutas. Co-supervisor: Dr Rita Busuttil
Project Site: Peter MacCallum Cancer Centre
Contact: A/Professor Alex Boussioutas T: +61 03 9656 1287 E: alexb@unimelb.edu.au;
Dr Rita Busuttil T: +61 03 9656 1287 E: Rita.Busuttil@petermac.org
Project Description: Gastric cancer (GC) is the fourth most common cancer globally and in many western countries is usually only diagnosed at advanced stage giving patients a 5-year survival rate of less than 20%. GC has distinct premalignant stages that have significant propensity to progress. The premalignant cascade consists of easily identifiable histological stages from chronic atrophic gastritis (ChG), intestinal metaplasia (IM) and dysplasia. The progression through these stages, particularly IM, takes years, offering a large window of opportunity to intervene. However not all patients with IM will progress and selection of patients for high-risk surveillance would reduce the burden of unnecessary screening, patient anxiety and improve outcomes due to early detection of disease.
Relatively little is known about the key genetic events leading to IM. Our laboratory is currently in the process of completing the first comprehensive analysis of IM in the world and seeks to identify candidate genes involved in the progression of IM to GC that can be used to reliably predict the progression to GC in humans by using a genomics based approach. Identification of such genes offers an opportunity to study the molecular mechanisms involved and pinpoint targets for prevention and therapy. The aim of this project is validate these candidate genes using an independent data set and then characterizing these genes using functional assays and animal models.
We are looking for motivated students (both Honours and PhD students) to strengthen our group. The project will use broad range techniques including bioinformatics, cell culture, animal models and molecular biology.
Role of the Tumour Microenvironment in Gastric Cancer
Supervisors: A/Professor Alex Boussioutas. Co-supervisor: Dr Rita Busuttil
Project Site: Peter MacCallum Cancer Centre
Contact: A/Professor Alex Boussioutas T: +61 03 9656 1287 E: alexb@unimelb.edu.au;
Dr Rita Busuttil T: +61 03 9656 1287 E: Rita.Busuttil@petermac.org
Project Description: Gastric cancer (GC) is the fourth most common cancer globally and 7th in incidence in Australia. It has a poor survival rate which can be attributed to the advanced stage at diagnosis in most patients. The molecular and cellular mechanisms underlying the development of GC are not well described.
Traditionally cancer research involved studying the cancer cell itself. More recently, there has been growing interest in studying the normal cells and molecules which surround the cancer cell. This tumour microenvironment consists of a variety of stromal cell types including cells such as fibroblasts. It is believed that the dynamic communication between tumour cells and the surrounding cell types may play a major role in cancer initiation, progression and establishment of metastatic disease. The aim of this project is to investigate tumour-stromal interactions in gastric cancer utilizing established and primary cell lines. Once the molecular pathways by which a tumour cell progresses has been elucidated it is possible that these processes could be exploited in the development of novel therapeutics.
This project will use a broad range of techniques such as live cell microscopy, cell culture techniques and siRNA to interrogate the function of gene products that influence tumour-stroma communication.
Our previous genomic experiments has provided us with a number of exciting candidate genes that may be involved in this interaction. This is novel research that may have a major benefit to our understanding of cancer and improve patient outcomes.
Elucidating the role of mesenchymal stem cells in promoting metastasis of ovarian cancer cells - also offered as MBiomedSc
Supervisors: Dr Bill Kalionis (Pregnancy Research Centre, RWH), Dr Nuzhat Ahmed (The Fiona Elsey Cancer Research Institute, Ballarat).
Project Site: Work will be conducted at the laboratories of the Royal Women’s Hospital
Contact: Dr Bill Kalionis, Pregnancy Research Centre, RWH. T: 8345 3748 E: bill.kalionis@thewomens.org.au
Hypothesis- Mesenchymal stem cells (MSC) residing in ovarian stroma or in non-ovarian tissues can promote ovarian cancer metastasis.
Specific aims- (i) To determine whether MSC derived from ascites of ovarian cancer patients or those derived from human placenta can alter the growth, invasive and ovcasphere forming abilities of ovarian cancer cell lines in vitro; & (ii) to determine if MSC can alter the response of ovarian cancer cell lines to chemotherapy.
Background/Rationale: MSC within tumour stroma are derived from the resident tissue or from the circulation or recruited from tissues not related to the tumour. Few recent reports have shown MSC to promote cancer metastasis by initiating paracrine signalling or through enriching the population of ‘tumour initiating cells’ commonly known as ‘cancer stem cells’. About 75% of ovarian cancer patients diagnosed at an advanced-stage have peritoneal dissemination in the form of ascites containing single cells and tumour cellular aggregates. Recent data in our laboratory suggests that MSC forms an important component of ascites of ovarian cancer patients. This warrants the need to study the biological alterations (phenotype) induced by MSC on the growth, invasiveness and response to chemotherapy in ovarian cancer cell lines in vitro.
Outcomes/Benefits: This proposal will compare the inherent traits and chemotherapy response of ovarian cancer cells in the presence and absence of MSC. MSC will be isolated from the ascites of ovarian cancer patients as well as from the placenta of women undergoing caesarean section. Differences in the biological phenotype of ovarian cancer cells in the presence and absence of MSC will be assessed by methods such as Western blot, quantitative PCR, immunofluorescence, flow cytometry, MTT and 3H-thymidine uptake assays. The identification of these changes/molecules may lead to the development of novel therapeutic targets either independently or by inhibiting the effects of MSC on ovarian cancer cells.
Human ethics application (HEC#09/09) has been approved by the Royal Women’s Hospital Human Ethics Committee.
TGF-signalling and cancer development
Supervisors: Dr. Hong-Jian Zhu, Dr. Rodney Luwor, Bo Wang, Catherine Winbanks
Project Site: Cancer Signalling Laboratory, Department of Surgery (5th Floor, Clinical Sciences Building, The Royal Melbourne Hospital)
Contact Dr Hong-Jian Zhu T: 8344 3025 E : hongjian@unimelb.edu.au;
Dr Rodney Luwor T: 8344 3027 E: rluwor@unimelb.edu.au
Project description: Traditionally, key-lock or on-off models dominate the molecular understanding of cellular signalling and disease development, with most studies focusing on linear molecular signalling cascades. With the advent of large scale molecular techniques such as proteomics and microarrays, cross-talk between signalling networks has been implicated to play critical roles in cancer development. It challenges the physiological validity of the switch on-off model. Our lab, using molecular, cellular and gene targeted animal models as well as human patient samples, has established that the moderation of signalling sensitivity by other pathways, rather than a black-white switch on-off, specifically of the TGF (Transforming Growth Factor-) signalling pathways determines cancer progression. These findings have been published in top-ranking biomedical journals including Nature Medicine (11:845-52, 2005). Given the medical significance, current works in our lab are supported by 4 NHMRC and 1 Cancer Council grants totalling more than $2 million.
This lab aims to understand the molecular fundamentals of TG signalling mis-regulation and its causation effect on early tumor development and late tumor invasion and metastasis. In particular, we focus on the few major oncogenic molecular pathways’ cross-talk with TGF signalling in various stages and types of cancer development. Concurrently, we are also devising strategies utilizing our unique molecular insights to convert tumor-causing signalling to directly tumor-killing.
The following projects are designed for students to participate in forefront cancer research and to achieve excellent novel results in a relative short time frame (9-10 months).
Project A: Converting oncogene signalling to tumor killing in brain cancer
Project B: Stat3 mediated impairment of TGF - signalling in head&neck and breast cancer
Project C: Targeting TGF - signalling expansion in brain tumor invasion
Project D: Regulation of TGF - signaling by Wnt pathway in the development of colon cancer
Techniques to be used: Cell culture, reporter assays (gene expression), adenoviral work, molecular biology, Western and Northern blotting (protein and mRNA respectively), thymidine assays (cell proliferation), real-time PCR, immunofluorescence and immunohistochemistry, siRNA (gene silencing), animal imaging.
Preferred background and quality of student: biochemistry, pathology, medical sciences; good nature as a person, passionate and dedication in research, perseverance in problem solving.
Integrated Genomics of metastatic, lethal Prostate Cancer - also offered as MBiomedSc
Supervisors: A/Prof Chris Hovens and Dr Niall Corcoran
Project Site: Department of Surgery (RMH), 5th Floor, Clinical Sciences Building and Prostate Cancer Epworth Hospital, Richmond
Contact: A/Prof Chris Hovens T: 9342 7703/4 E: cbhovens@gmail.com
Project description: With over 20,000 diagnoses per year, Australian men have the highest rate of prostate cancer in the world. Currently our research team are addressing some of the most important clinical questions today in prostate cancer management using genomics and proteomics experimental designs. We have access to human tissue samples taken from men undergoing surgery together with the clinical informatics that indicate their outcomes, therefore this project will have high clinical relevance and impact.
The aim of the project is to delve deeper into our analyses of the genomics of prostate cancers from patients who have either died or who have metastatic disease. We have identified a number of candidate regions and changes that may be key to driving prostate cancer metastasis and subsequent lethality. Projects will focus on validating these findings in independent cohorts of patients and starting to examine experimentally the biology behind the observed changes and how they impact on tumor behaviour. Research students will work within a team of experienced scientists and have access to scientific expertise and equipment through our department, associated institutions and existing collaborations with leading urologists. Our commitment to academic excellence and links with the Australasian Prostate Cancer Conference, one of the largest urology meetings in the region, ensure additional exposure to publication and presentation opportunities for the motivated researcher.
Benefits to student: Molecular and clinical research in the one, multi-collaborative project encompassing basic research and clinical interaction.
Requirements for students: Dedicated, passionate and committed. Must have done very well academically.
Double Jeopardy - dead prostate cancer cells can't recur - also offered as MBiomedSc
Supervisors: A/Prof Chris Hovens, Dr Michael Clarkson
Project Site: Department of Surgery (RMH), 5th Floor, Clinical Sciences Building
Contact: Dr Michael Clarkson E: mclarkson@unimelb.edu.au
Background/Rationale: The critical role of androgen (testosterone) signalling in Prostate cancer (CaP) is unequivocally supported by the fact that this cancer can be effectively treated by surgical castration or drugs that disrupt androgen action or production. While androgen deprivation therapy (ADT) provides significant respite from prostate cancer progression, treatment resistant tumors recur with high frequency and are generally associated with poor outcome. We hypothesise that cells are initially rendered “dormant” by ADT and in this state they accumulate mutations that allow them to escape from growth suspension to recommence proliferation. Our recent results, and some published studies, indicate that this dormant state might render cells more sensitive to killing by other agents. If this is true then ADT in combination with a complementary drug has the potential to substantially improve patient treatment and outcome by killing prostate cancer cells rather than just rendering them dormant.
Project Description: We have established cell lines that contain a newly developed marker for programmed cell death (apoptosis) that turns fluorescent red when the cell death program is initiated. We will use this line to screen a library of drugs for their ability to induce cell death in combination with ADT. Our studies with patient derived samples has also provided some clues about what pathways would be best to target. We will prioritise these pathways. In addition to cell based studies we are using an ex vivo system that allows us to culture patient tissue samples, treat them with drugs and examine response.
Skills/Techniques: Advanced cell biology techniques, high throughput semi-automated drug screening, high throughput microscopy and analysis (Operetta system), ex vivo tissue culture, immunohistochemistry, qRTPCR, western blotting.
Benefits to student: Molecular and clinical research in the one, multi-collaborative project encompassing basic research and clinical interaction.
Requirements for students: Dedicated, passionate and committed.
STAT3-mediates Resistance to EGFR targeted therapy in Cancer
Supervisors: Dr Rodney Luwor
Project Site: Dept of Surgery, Royal Melbourne Hospital
Contact: T: 8344 3027, E: rluwor@unimelb.edu.au
Project description: During physiological processes the intracellular protein Signal Transducer and Activator of Transcription 3 (STAT3) is activated by many growth factors and cytokines (e.g. EGF, IL-6, IL-11…etc) resulting in transcription of many genes involved in a multitude of cellular processes. However, uncontrolled or un-attenuated STAT3 phosphorylation and activation results in cancer initiation, progression and metastasis of many tumour types. Therefore, understanding how STAT3 is regulated or controlled within the cell is pivotal for cancer biology and may allow greater scope for therapeutic intervention into STAT3-driven tumourigenesis. Recently, we have shown that many colon cancer cell lines are resistant to a clinically approved anti-EGFR monoclonal antibody, Cetuximab. However, blocking STAT3 activation could re-sensitize these tumour cells to the growth inhibitory effects of cetuximab. Therefore we hypothesise that activation of STAT3 provides an alternative mechanism for resistance to EGFR targeted therapy and targeting IL-6, IL-11 or STAT3 can overcome this resistance. Our Honours/Masters program offers students a choice of projects within our STAT3 signalling research. This project seeks to evaluating novel regulators of STAT3 and determining whether these regulators have a role in driving STAT3-mediated resistance to anti-EGFR therapy. We will also assess the potential of delivering novel inhibitors to STAT3 to inhibit cancer growth and resistance to anti-EGFR agents. Furthermore, this project has the scope to evolve into a PhD project starting in 2018/19 pending the ability of the incumbent student.
Skills acquisition: Cell biology techniques including Cell transfections, western blotting, immunofluorescence staining and confocal microscopy, luciferase reporter assays, RT-PCR and potentially animal handling and injecting
The Molecular Determinants of BRain Tumour Progression and Resistance to Therapy
Supervisors: Dr Rodney Luwor, and Dr Theo Mantamadiotis
Project Site: Dept of Surgery, Level 5, Clinical Sciences Building, Royal Melbourne Hospital (also Dept of Dept of Pathology, University of Melbourne)
Contact: Dr Rodney Luwor; T: 8344 3027, E: rluwor@unimelb.edu.au
Project description: Glioblastoma Multiforme (GBM) is the most devastating and aggressive tumour of the central nervous system accounting for approximately 50% of all primary brain tumours. Surgery, followed by irradiation and concomitant and adjuvant temozolomide is now considered the standard of care for GBM patients. However, the overall prognosis remains abysmal for GBM patients with a median survival of only 15 months. The presence of pre-existing intrinsic resistance and the ability of GBM tumours to develop or acquire resistance represents a major challenge to successful treatment. Resistance to temozolomide is common; however the exact mechanisms and key molecules that mediate resistance are not clearly elucidated.
Our Honours/Masters program offers students a choice of projects within two major themes based on our GBM-orientated research. Firstly, projects will be designed to explore novel molecular mediators of GBM proliferation, migration and invasion and potentially evaluate treatment strategies to overcome GBM progression. Alternatively, students will perform projects that seek to explore potential molecular candidates in mediating resistance to current therapy. Both these project directions will ultilise a large set of brain tumour cell lines and human brain tumour tissue and serum archived within our department. Furthermore, this project has the scope to evolve into a PhD project starting in 2018/19 pending the ability of the incumbent student.
Skills/Techniques acquired:Cell biology techniques including Cell transfections, western blotting, immunohistochemistry, confocal microscopy, luciferase reporter assays, RT-PCR, migration and invasion assays and potentially animal handling and injecting.
Defining the Epidermal Growth Factor Receptor Signaling Network in Brain Tumour Stem Cells
Supervisors: Rodney Luwor and Dr. Theo Mantamadiotis
Location: Dept of Surgery RMH and Dept of Pathology
Contact: Dr Rodney Luwor E: rluwor@unimelb.edu.au;
Dr. Theo Mantamadiotis: theom@unimelb.edu.au;
Project description: Aberrant cell signalling underlies the loss of growth control, enhanced survival, inappropriate migration and drug resistance in tumour cells. In malignant brain tumours such as Glioblastoma Multiforme (GBM), a number of key components of signaling pathways are known to be inappropriately activated due to mutations. The epidermal growth factor receptor (EGFR) is mutated in about 30% of GBM patients. The downstream effects of the EGFRvIII mutation in brain tumour cells leads to a spectrum of cell signaling events which promote the transcription of many genes which orchestrate pro-tumorigenic cell characteristics. A key transcription factor which lies downstream of the EGFR pathway is CREB, which has recently been shown to have a role in regulating cell human brain tumour cell growth. In this project, the activation of CREB, in a variety of human tumour cell lines, including cancer stem cells which express wild-type EGFR and EGFRvIII, will be examined using cell and molecular techniques. The CREB-dependent transcriptome will also be investigated to understand whether there is a distinct set of EGFRvIII CREB-dependent target genes compared to wild-type EGFR.
Regulationof invadopodium function and involvement in cancer cell invasion
Supervisors: Dr Stanley Stylli
Project Site: Dept of Surgery, Level 5, Clinical Sciences Building, The Royal Melbourne Hospital
Contact: Dr Stanley Stylli; T: 9035 5236, E: sstylli@unimelb.edu.au
Project description: The cause of death for up to 90% of cancer patients is the metastatic spread of cancer cells from the primary tumour and the subsequent development of a secondary tumour or tumours at a distant site. Many patients normally present with symptoms relating to the localized primary disease which can be managed with a number of therapies including surgery, radiation and chemotherapy. But numerous patients return post-therapy with a developed metastatic lesion at a secondary site. The dissemination of metastatic cells involving the migration and infiltration of these invasive cells is commonly thought to require two events. This includes increased cellular motility, accompanied with the proteolytic processing of the extracellular matrix (ECM) and subsequent penetration through the surrounding tissues.
A property shared by several types of tumour cells with high invasive or metastatic potential is an ability to form structures known as invadopodia. They are dynamic actin-rich protrusions which adhere to and proteolytically degrade ECM substrates via the activities of secreted extracellular proteases. Functional (matrix-degrading) invadopodia have been observed in tumour cell lines and primary tumour cells derived from ex vivo tumour specimens from a number of cancers, primarily head and neck squamous cell carcinoma and breast cancer specimens. This suggests that there is a possible role for invadopodia in tumour cell invasion of many cancers.
Invadopodia formation and function are dependent on multiple proteins and signaling pathways. Therefore understanding how invadopodia are regulated and controlled within a tumour cell is essential and strategies aimed at disrupting invadopodia could form the basis of novel anti-invasive therapies for treating cancer patients in the future. This honours project will involve studies that explore the role of a number of invadopodia proteins in cancer cells, how they contribute to their invasive/metastatic phenotype and ultimately influence response to treatment protocols.
Skills/Techniques acquired: Cell Biology techniques including cell culture and cell transfections (overexpression and siRNA gene silencing), western blotting, zymography, immunofluorescence and immunohistochemistry, confocal microscopy, migration/invasion assays, reporter assays.
Molecular biomarkers for Human Papillomavirus-related cancer progression
Supervisors: Dr Alyssa Cornall, Professor Suzanne Garland
Project Site: Women's Centre for Infectious Diseases (RWH), Bio21 Institute
Contact: Dr Alyssa Cornall E: alyssa.cornall@mcri.edu.au
Profject description: The majority of cancers of the cervix (>99%) and the anal canal (>80%) are associated with Human Papillomavirus (HPV) infection, yet not all HPV infections lead to cancer. Cancer development is preceded by certain molecular changes; these include epigenetic modifications such as methylation of viral gene promoters, and changes to the expression of viral and cellular gene products. Using techniques such as laser capture microdissection (LCM), HPV genotype sequencing, quantitative PCR, sequencing of methylation patterns and analysis of p16 expression, this project will involve the characterization of pre-cancerous lesions based on molecular changes to viral gene regulation, in order to identify molecular markers that can more accurately predict progression to cancer.
Human Papillomavirus (HPV) prevalence in Australia following a national vaccination program
Supervisors: Dr Dorothy Machalek, Dr Alyssa Cornall, Professor Suzanne Garland
Project Site: Department of Microbiology and Infectious Diseases, RWH, Parkville Campus
Contact: Dr Dorothy Machalek: Dorothy.machalek@mcri.edu.au;
Dr Alyssa Cornall: alyssa.cornall@mcri.edu.au
Project description: Human Papillomavirus (HPV) is the causative agent for cervical and a proportion of other anogenital cancers, and of genital warts. In 2007, Australia became the first country to introduce a fully government-funded National HPV Vaccination Program and is now vaccinating boys and girls against HPV genotypes 6, 11, 16 and 18.
Following the introduction of the vaccination program, surveillance of HPV genotypes in the population is required to monitor the impact of the vaccination program in a real world setting. This project will involve genotype testing and analysis of clinical samples collected as part of the National HPV Monitoring Program (called IMPACT). Self-collected genital samples from 18 to 35 year old men and women attending IMPACT sentinel clinics will be tested for the presence of HPV DNA. Data from women will help evaluate the direct effect of the vaccine on vaccinated and unvaccinated female populations, while data from men (most of whom will not have been vaccinated) will provide valuable baseline data on HPV prevalence in men. This project will involve sample logging and processing, DNA extraction, quality control testing, PCR and genotyping, data management and epidemiological data analyses
In vitro brain tumour model - studying epileptic seizure development and sensitivity to anti-cancer therapy
Supervisors: Dr Chris French, Dr Andrew Morokoff, Dr Rodney Luwor,
Professor Terence O’Brien
Project Site: Department of Surgery, Department of Medicine RMH, Melbourne Brain Centre
Contact: Dr Chris French - frenchc@unimelb.edu.au
Project description: Malignant brain tumours are notoriously difficult to treat and are often complicated by severe epileptic seizures. Research into therapies has been hampered by a limited range of model systems to explore pathogenesis and treatment of these tumours. We have developed an in vitro model of aggressive brain tumours using a rat brain culture technique. This uses several well-characterised human tumour cell lines as well as tumour “stem-cells” available in our laboratories. These are seeded into a section of brain maintained in tissue culture. The project has two aims – to examine the effects of conventional and novel treatments on the tumours as well as the development of epileptic seizure activity in the system. Seizure development will be assayed by electrophysiological recordings.
This novel technique in this project has the potential to provide important insights into the pathophysiology and treatment of brain tumours and tumour-related epilepsy.
Priorities and needs of women living with advanced cancer - also offered as MBiomedSc
Supervisors: Dr Jennifer Marino and Dr Michelle Peate
Project Site: Royal Women’s Hospital
Contact: E: jennifer.marino@unimelb.edu.au
Project description: Although the survival of patients with cancer has improved greatly over the past 30 years, between 2008 and 2012, a third of all patients with cancer survived less than five years. Generally, cancer research tends to focus on curative therapy, but many patients die of their cancer. These patients, not only have to cope with facing an incurable condition, but are often ‘forgotten’ or become ‘invisible’ in the context of this focus on survivorship outcomes. Many people who live with advanced cancer report a feeling of being seen negatively by society, and that they suffer from psychological, physical or financial problems for which they receive little support. Despite this, we know very little about the needs and priorities of people living with advanced cancer. This information is essential to inform clinical decision-making to maximise the quality of the life these patients have left – for some this is only a short time yet others will live with their cancer for many years. To aim of this project is to gather qualitative and quantitative data from advanced cancer patients, their families, and their providers to identify their needs, with the eventual goal of establishing clinical tools, including patient-reported outcome measures and useful tools that can improve the end-of-life experience of these patients and their families.
Benefits to student: This is a multi-collaborative project, so student will gain experience working in a multidisciplinary team. They will also have the opportunity to learn develop qualitative and/or quantitative research skills, gain an understanding of ethical procedures, be trained in high quality data management, collection and analysis processes.
Requirements for students: Looking for a dedicated, passionate, sensitive and committed student with a good academic record and strong writing and communication skills.
CANCER FERTILITY PRESERVATION
Fertility Issues in children and adolescents with cancer
Supervisors: Dr Yasmin Jayasinghe, Dr Lisa Orme, Dr Leanne Super
Project site: The Royal Children’s Hospital and The Royal Women’s Hospital, Melbourne
Contact: E: yasmin.jayasinghe@unimelb.edu.au
Project description: Fertility loss is one of the side effects of cancer treatment. Advances in reproductive technologies may one day offer children and adolescents with cancer, the possibility of future fertility through ovarian or oocyte tissue retrieval and storage prior to commencement of cancer therapy. However such treatments are regarded as investigational in children due to immaturity of gonadal tissue, and also pose unique clinical and ethical dilemmas with respect to informed consent and beneficience for the young person. It is now recommended that where cancer treatment poses a fertility risk, fertility preservation should be discussed with all patients, and with parents or guardians. Long-term survivors report dissatisfaction with the quality of such discussions, or have no memory of them. Over 95% of paediatric oncologists surveyed in Australia and New Zealand believe that centre-specific clinical protocols are necessary to establish standards of care. However such guidelines rarely exist. Furthermore there is little information on recovery of gonadal function post chemotherapy in children and adolescents, to further guide discussions regarding fertility options after chemotherapy.
Several sub-studies are available which may assist with the development of Fertility Preservation guidelines and improve patient outcomes at the Royal Children’s Hospital Melbourne, which include:
- An audit of fertility preservation consultations for patients seen at The Royal Children’s Hospital between 2002 and 2014. This project is ethics approved. Specifically the audit will report the proportion of subjects who underwent such discussions, the procedures offered, barriers to uptake of the procedures, and complications. .
- Evaluation of a ‘Fertility Preservation Toolkit’. This is a recently introduced resource for health providers, patients and families which aims to improve knowledge and awareness of fertility preservation options for patients and families by providing information in a standardized manner.
- Mining the haematology oncology database at the Royal Children’s Hospital to examine recovery of gonadal function according to cancer treatment in the young.
Benefits to student: A multi-collaborative project encompassing basic research and clinical interaction. Publication.
Requirements for students: Dedicated, passionate, sensitive and committed. Has done well academically.
Fertility after cancer predictor (FoRECAsT) study - also offered as MBiomedSc
Supervisors: Dr Michelle Peate, A/Prof Shanton Chang, Prof Martha Hickey
Project Site: Royal Women’s Hospital, Parkville
Contact: Dr Michelle Peate, mpeate@unimelb.edu.au
Project description: Breast cancer is the most frequently diagnosed cancer in reproductive aged women and many women are diagnosed before they have started or completed their families. Fortunately, survival from early breast cancer is almost at 90%. These women then need to deal with the consequences of treatment, such as potential infertility. Research has shown that fertility is a priority amongst these women and concerns about how cancer treatment impacts fertility may influence cancer treatment decisions. Thus, being able to provide women with information about how their fertility will be affected by treatment is important. This can help them to make decision around fertility preservation prior to starting adjuvant treatment. Whilst there is general information about the potential effects of cancer treatments on fertility, there is no mechanism for obtaining personalised information about likely fertility outcomes. Current "calculators" consider cancer type and treatment, but do not consider this in the context of a woman’s fertility prior to cancer treatment. The aim of this study is to develop an online fertility predictor targeted at young women with breast cancer. This ‘calculator’ will take into consideration both intrinsic individual fertility-related characteristics, and the likely impact of cancer treatment to produce a risk of infertility. This tool will be available to women in order to inform decision making around breast cancer treatments.
There are a number of projects available:
- Exploring needs and potential barriers for the FoRECAsT tool amongst younger women with breast cancer.
- Exploring needs and potential barriers for the FoRECAsT tool amongst medical oncologists.
- Determine usability of the FoRECAsT tool using a series of iterated wireframes.
- Evaluate the acceptability and usability of the functional FoRECAsT tool.
Benefits to student: This is a multi-collaborative project, so student will gain experience working in a multidisciplinary team. They will also have the opportunity to learn develop qualitative and/or quantitative research skills, data collection and analysis and a goal will be to author a peer-reviewed publication.
Requirements for students: Looking for a dedicated, passionate, sensitive and committed student with a good academic record and strong writing and communication skills.