CANCER RESEARCH STUDENT PROJECTS 2020

2 FROM OUR CANCER RESEARCH EXECUTIVE DIRECTOR

For 70 years, Peter Mac has been providing high quality treatment and multidisciplinary care for cancer patients and their families. Importantly, we house Australia’s largest and most progressive cancer research group, one of only a handful of sites outside the United States where scientists and clinicians work side-by-side.

Our research covers a diversity of topics that range from laboratory-based studies into the fundamental mechanisms of cell ransformation, translational studies that rovide a pipeline to the patient, clinical trials with novel treatments, and Peter Mac is committed to continue to support and build our research aimed to improve supportive care. broad research enterprise including fundamental research, and I am in no doubt that strong discovery-based research labs The proximity and strong collaborative links of clinicians and and programs are essential for us deliver the best care for our scientists provides unique opportunities for medical advances patients. to be moved from the ‘bench to the bedside’ and for clinically orientated questions to guide our research agenda. As such, If you undertake your research at Peter Mac, you will be our research programs are having a profound impact on the supported by a pre-eminent academic program, driven by understanding of cancer biology and are leading to more internationally renowned laboratory and clinician researchers, effective and individualised patient care. with a strong focus on educating future generations of cancer clinicians and researchers. As Executive Director Cancer Research, it is my mission to strategically drive Peter Mac’s standing as one of the leading You have the opportunity to work at the forefront of cancer cancer centres in the world by enhancing our research care and make a contribution to our research advances. outputs, increasing our talent pool and enabling existing and new areas of research excellence. Welcome to Peter Mac Cancer Research.

I firmly believe that our model of research-driven cancer care is the right one and Peter Mac is uniquely positioned to expand this paradigm both internally and with our external partners. Professor Ricky Johnstone Executive Director, Cancer Research

3 CONTENTS

Peter Mac’s comprehensive and internationally renowned cancer researchers seek fundamental biological and biomedical discoveries, and aim to facilitate the development and application of these discoveries to their full therapeutic potential. Critical to this aim is our ability to recruit outstanding staff and students to drive our innovative basic and translational research. This book provides an overview of project directions available for students across different disciplines, all with a focus on cancer and changing treatment outcomes for patients.

About Our Research Laboratory Research ‘Nothing but the best Clinical Research is good enough for the Platform Technologies Research Programs treatment of cancer’ Research Education Comprehensive Cancer PhD Program Sir Peter MacCallum Becoming a Student Project descriptions (Alphabetical by Research group)

Peter MacCallum Cancer Centre 1 ABOUT OUR RESEARCH

Peter Mac is one of the world’s leading cancer research, education and treatment centres globally and is Australia’s only public hospital solely dedicated to caring for people affected by cancer. We have over 2,500 staff, including more than 600 laboratory and clinical researchers, all focused on providing better treatments, better care and potential cures for cancer.

Dedicated research is the key to better treatments, better Peter Mac is home to many large, group [cohort] studies care and cures for cancer. This is a place where normal collecting biospecimens, blood samples and survey data days are extraordinary – as are the people we care for. from people with cancer to build large open-access Each day our team strives to provide the very best in resources for innovative research projects. Some studies cancer care, better treatments and potential cures for all also collect information from people who have never had people affected by cancer. cancer. Cohort studies give our researchers, and researchers Globally, we are facing one of the most pivotal times in worldwide, access to a vast array of ethically collected the pursuit of cancer cures, and Peter Mac stands at its clinical samples and associated clinical data. Our cohort forefront. Together, we aim to lead a new era of cancer studies include: prevention, care and discovery, supported by state- • Australian Ovarian Cancer Study (AOCS) of-the-art facilities at our home within the Victorian Comprehensive Cancer Centre building, • BROCADE - BReast Origin CAncer tissue DonatEd after death LABORATORY RESEARCH • CASCADE - Cancer Tissue Collection After Death Peter Mac’s comprehensive and internationally renowned • Cancer 2015 cancer research laboratories seek fundamental biological • International Sarcoma Kindred Study and biomedical discoveries, and aim to facilitat the development and application of these discovereis to their • kConFab full therapeutic potential. • Lifepool Peter Mac is home to over 450 laboratory-based scientists • Melanoma Research Victoria (MRV) and support staff, including more than 150 higher degree (mainly PhD) and Honours students. • SUPER - Solving cnacer of unkonwn primary Supported by nine core technology platforms, our research • ViP: Variants in Practice laboratories are organized into programs of laboratory- based and translational research: CLINICAL RESEARCH • Cancer Genetics & Genomics https://www.petermac.org/research/programs/ • Cancer Immunology clinical-research-areas-programs • Cancer Metabolism Peter Mac is committed to linking patient care with cancer research. Our clinician researchers take thier observtions • Cancer Therapeutics from the clinc and plan thier research directions with • Computational Biology patients in mind. There are many specialised groups actively engaged in • Gastrointestinal Cancer clinical research. Our aim is to improve treatment, and • Organogenesis and Cancer care and experience outcomes of cancer patients and their support networks. • Prostate Cancer Our clinician researchers work across all tumour types • Translational Haematology and services: the Bone and Soft Tissue, Breast, Cancer of Unknown Primary, Colorectal, Gynae-Oncology, • Tumour Angiogenesis and Microenvironment Haematology, Head and Neck, Lung, Melanoma and Skin,

Peter MacCallum Cancer Centre 2 ABOUT OUR Treatment informed by research, and RESEARCH research informed by treatment, is the key to progressing better cancer care.

Neuro-Oncology, Paediatric and Late Effects, Upper exposure to effective therapy while reducing exposure to Gastrointestinal, and Uro-Oncology Services. normal tissue. Clinical services research includes the following areas: Radiation Oncology Research Australian Cancer Survivorship Centre (ACSC) Radiation oncology research aims to provide the most up- The ACSC aims to better understand the issues that to date and effective evidence-based treatment for patients survivors experience and their needs, and develop and test with cancer who require radiotherapy as part of their interventions that improve survivors’ well-being. treatment. Cancer Allied Health (CAH) Cancer Surgery & Anaesthesia Research CAH research is focused on delivering high-quality This clinical research group is working to improve the evidence-based services to our patients, their families and technical aspects and impact of cancer surgeries, and carers. to improve the delivery and efficacy of anaesthesia and interventional pain medicine. Cancer Experiences Research Victorian Epigenetics Group (VEG) This group develops novel, patient-centred strategies and interventions. Their research focus is on communication, The VEG supports clinical trials of “epigenetic drugs” for health literacy, emotional and physical functioning, care patients with blood cancers through pre-clinical evaluation, coordination, education information, well-being for survival novel biomarker development and early phase clinical and living well at the end of life. trials of new drugs. Familial Cancer Centre (FCC) Biostatistics and Clinical Trials (BaCT) The Parkville FCC works with families to investigate Peter Mac is the leading biostatistical centre focusing hereditary cancer syndromes and how they can better on cancer clinical trials in Australia. The centre provides manage their cancer risk. statistical expertise for national cancer trials groups Imaging and Diagnostic Research including the Trans Tasman Radiation Oncology Group (TROG) and the Australasian Leukaemia and Lymphoma Imaging and diagnostic research is conducted in Peter Study Group (ALLG). Mac’s Centre for Cancer Imaging. Our researchers image tumours to develop new therapies and improve imaging Radiation and Cancer Imaging technologies for cancer patients. State-of-the-art radiation and imaging equipment underpins Peter Mac’s efforts to enhance the delivery Infectious Diseases & Infection Control (IDIC) of radiation therapy, both as a single modality and, Peter Mac’s IDIC research group aims to improve cancer increasingly, as a combined modality therapy using novel outcomes through enhanced infection services. This group chemotherapy and targeted therapy agents. is home to the NHMRC National Centre for Infections in Cancer - an integrated health care program for reducing Clinical Trials infections in cancer. Clinical trials are central to Peter Mac’s commitment to finding more effective cancer treatments and improving ONTrac care for people with cancer, their families and carers. This multidisciplinary research group is committed to With more than 200 clinical trials active every year, improving the understanding and knowledge of the health Peter Mac has a comprehensive network of clinical trials outcomes of young people living with cancer. support in place, bringing together laboratory researchers, Pain & Palliative Care (PPC) Research medical, surgical and radiation oncologists, many of whom PPC research focuses on symptom control, end-of-life are clinician-researchers, pathologists, pharmacists, care including advance care planning, and models of geneticists and clinical trials nurses. integration of palliative and acute care. The Parkville Clinical Trials Unit (PPCTU) incorproates Physical Sciences Research the cancer clinicla trials services of Peter Mac, the Royal Melbourne Hospital, and the Royal Women’s Hospital. Physical sciences research is focused on the delivery of cancer radiotherapy treatments that increase tumour

3 PLATFORM TECHNOLOGIES grant applications and the analysis and publication of genomic and transcriptomic data. Data types analysed by Our core facilities and platform technologies are the the core include whole-exome sequencing, targeted re- backbone of our research and ensure that the researchers sequencing, RNA-sequencing, ChIP-sequencing, NanoString are outfitted with the equipment and expertise needed to and various types of microarray data. facilitate their research. https://www.petermac.org/research/core-facilities/ An important role of the core platform technologies is to bioinformatics also identify, import, and develop new technologies. Peter Mac’s core technologies and expertise are also made available to external researchers on a collaborative or cost Flow Cytometry and Cell Sorting recovery basis, thereby increasing research output in the This facility provides researchers with access to state-of- the-art equipment and expertise that enables isolation, wider bioscience community. separation and analysis of cell populations based on their biological and therapeutic properties. Flow cytometry is a powerful technique for the analysis Centre for Advanced Histology and Microscopy of individual cells within complex populations. It is used in both research and clinical settings, and has an important The Centre for Advanced Histology and Microscopy (CAHM) role in the translation of knowledge from the research underpins a multitude of cancer research projects with setting to the clinical area (translational research). four core platforms: https://www.petermac.org/research/core-facilities/flow- • Histology cytometry • Optical Microscopy: including laser scanning confocal microscopes, a multi-modal super resolution microscope and multiphoton microscope, a dual Functional Genomics laser multiphoton microscope, and a laser capture Want to work with CRISPR? Want to knock down gene microscope. expression? Interested in growing your cells in 3D? Thinking about finding the next generation drug that • Electron Microscopy, inclusive of both transmission targets your disease of interest? How about quantifying and scanning electron microscopy. that cellular phenotype you are working on or the • Image Analysis, and Histology. expression of a series of proteins? Researchers utilising CAHM receive support, training and You can do all this and more in the Victorian Centre advice from expert technical scientists. for Functional Genomics (VCFG) on Level 11 using the sophisticated liquid handling automation, high content https://www.petermac.org/research/core-facilities/centre- microscopy and specialised analysis pipelines, the world- advanced-histology-microscopy first 3D bioprinter that embeds cells in a scaffold and our Reverse Phase Protein array platform. The VCFG team Bioinformatics Consulting Core are highly experienced technical experts in the areas of high throughput RNAi, CRISPR and compound screening The Bioinformatics Consulting Core provides services and coupled with many different types of functional readouts know-how for the analyses of high-throughput genomics to represent your cell biology and disease state. They have data. Our team of bioinformaticians and postdoctoral scientists work alongside laboratory and clinical researchers and contribute to their experimental design,

Peter MacCallum Cancer Centre 4 recently installed the 3D bioprinter to grow cell lines and Tissue Bank patient derived material in 3D in high throughput allowing The Tissue bank is a member of the Victorian Cancer personalised medicine approaches to drug discovery. Biobank, providing researchers with ethically collected, The VCFG operates a ‘researcher-driven - staff assisted’ high quality human tissue, blood and data samples for their model whereby someone from the team works with you investigative projects. It also supports clinical trials at Peter through the process of your project, trains you to run Mac by processing and storing blood and tissue specimens some of the instrumentation and assists in analysis and in accordance with trial-specific protocols. interpretation. The opportunities are vast, it really just https://www.petermac.org/research/core-facilities/tissue- requires your imagination! bank https://www.petermac.org/research/core-facilities/ victorian-centre-functional-genomics Research Laboratory Support Services Research Laboratory Support Services (RLSS) provides a Molecular Genomics centralised, comprehensive range of services that support The Molecular Genomics Core facility offers researchers the researcher’s needs in a timely and cost effective access to state-of-the-art genomics technology platforms, manner. This includes Media Kitchen, Labware Services and providing service and expertise in conducting genomics Research Store. experiments. Genomics technologies are extremely powerful tools for discovering mutations in genes implicated in cancer. The facility operates three major Transgenic and SPF Facility platforms: Illumina Sequencing, Nanostring nCounter and We currently breed and maintain approximately 20,000 QX200 Droplet Digital PCR. mice, representing over 130 different strains of transgenic https://www.petermac.org/research/core-facilities/ and gene-targeted mice. molecular-genomics Peter Mac’s Animal Ethics Committee (AEC) has an important role in overseeing the ethical conduct of any work involving the use of animals for scientific purposes, Research Computing Facility conforming to the NHMRC Australian Code of Practice for The Research Computing Facility is responsible for the Care and Use of Animals for Scientific Purposes. administering Peter Mac’s Computing Cluster and Linux environment, providing leadership in the area of data governance, managing the Research Data Repository/ Archive, administering cloud computing resources, and providing specialised software solutions and/or systems to support research. The facility also provides training for the software systems they administer and general bioinformatics. https://www.petermac.org/research/core-facilities/ research-computing-facility

5 CANCER RESEARCH PROGRAMS

Organogenesis and Cancer Program https://www.petermac.org/research/programs/organogenesis-cancer

Research Labs: Despite being a fundamental part of life, we still lack a clear understanding of how individual organs know how to grow to the • Louise Cheng right size and maintain this size. The roles of stem and progenitor • Andrew Cox cells in the growth of different organs are also unclear, as is the impact of diet and nutrition on organ growth. To investigate these • Kieran Harvey questions our program leverages the unique strengths that are • Ben Hogan offered by different experimental systems including Drosophila, zebrafish, mice and organoid cultures. We also collaborate The primary focus of the Organogenesis & Cancer with clinicians from within the VCCC network to examine how program is to investigate the process of organ deregulation of organogenesis signalling networks drive cancers development and how failure of organogenesis such as melanoma, mesothelioma, glioblastoma and hepatocellular contributes to cancer. carcinoma.

Cancer Genetics and Genomics Program https://www.petermac.org/research/programs/cancer-genetics-genomics -program

Research Labs: The Cancer Genetics and Genomics program applies genomic technologies to large patient cohorts, with a particular focus on • David Bowtell breast, ovarian and prostate cancer. Familial (KConFab, ViP) and • Kara Britt population-based (Lifepool) breast and ovarian (Australian Ovarian Cancer Study) cancer cohorts are embedded in the program and are • Ian Campbell highly enabling of the research program due to the large numbers • Kylie Gorringe of patient samples with rich clinical information and associated biospecimens. Cancer is fundamentally a polygenic disorder, imparted by germline and somatic mutation. More recently the program has established CASCADE, a unique With advances in DNA sequencing and other rapid autopsy study that provides an enabling platform for a variety genomic technologies, it is feasible to obtain of solid and haematological malignancies. Sophisticated genomics, high-dimensional genomic information about an functional genetics and bioinformatics capabilities are also highly individual patient’s tumours and relate this to enabling of the program. clinical outcome.

Cancer Immunology Program https://www.petermac.org/research/programs/cancer-immunology -program

Research Labs: The Cancer Immunology Program is identifying ways in which the immune system can be harnessed to prevent and control cancer. • Paul Beavis • Jane Oliaro We are interested in the very early stages of how immune cells • Phil Darcy • Sarah Russell can pick up and respond to the presence of cancer cells. We have • Belinda Parker • Tony Tiganis demonstrated that specific toxins made by “killer T cells” can prevent the onset of certain cancers (immune surveillance), and are • Ricky Johnstone • Joe Trapani developing genetic technologies to modify and expand the activity • Paul Neeson • I lia Voskoboinik of these cells to treat established malignancies. In addition, we are defining the molecular means by which new classes of anti-cancer drugs kill cancer cells, so that rational choices can be made on the most appropriate cancer chemotherapy for a patient.

Peter MacCallum Cancer Centre 6 CANCER RESEARCH PROGRAMS

Cancer Therapeutics Program Gastrointestinal Cancer Program https://www.petermac.org/research/programs/cancer-therapeutics -program https://www.petermac.org/research/programs/gastrointestinal-cancer-program

Research Labs: available within the Peter Mac to discover, develop, characterise Research Labs: This Program has developed a world-class multi-disciplinary translational research program that responds to the needs of and refine novel cancer therapeutics for clinical use. • Wayne Phillips • Kristin Brown patients by (i) addressing critical clinical questions related to • Rob Ramsay treatment and management of gastrointestinal cancer, (ii) exploring • Charbel Darido This integrated program allows insight into fundamental aspects the cellular and molecular biology underlying the development and of cancer biology through the identification of novel tumour- • Alex Boussioutas • Sarah-Jane Dawson progression of gastrointestinal malignancies, and (iii) actively suppressor and tumour-initiating genes. We explore the • Nicholas Clemons translating laboratory findings into the clinic. • Shom Goel functional relationships between altered cancer genetics and • Rodney Hicks aberrations to the cancer epigenome, and a deeper understanding of the molecular events that drive oncogenic The program has a focus on gastric, oesophageal, colorectal, and • Sherene Loi Focussing on clinical, preclinical, and basic science signalling networks. These findings serve as a basis for anal cancers, and has strong clinical links with a surgical research research across all cancers of the gastrointestinal team led by Professor Sandy Heriot and additional surgeons and • Grant McArthur extensive translation-based studies to determine the potential tract (including oesophageal, gastric, colorectal and therapeutic benefit of interfering with, or augmenting the activity oncologists within the Victorian Comprehensive Cancer Centre • Belinda Parker anal cancers). of key proteins involved in these signalling networks through alliance, offering extensive training opportunities for postgraduate students, postdoctoral fellows and clinicians in basic, translational, • Ben Solomon pharmacological intervention. and/or clinical research. The Cancer Therapeutics Program aims to integrate various basic research activities, platform technologies, and pre-clinical model systems Tumour Angiogenesis and Microenvironment Program Translational Haematology Program https://www.petermac.org/research/programs/tumour-angiogenesis-microenvironment -program https://www.petermac.org/research/programs/translational-haematology-program Research Labs: The interaction of these cells types with tumour cells can either support or inhibit tumour progression. The spread of cancer to • Steven Stacker Research Labs: The Translational Haematology Program contains a diverse set lymph nodes and distant organs is a critical aspect of cancer of laboratories that focus on understanding the molecular • Stephen Fox progression and is facilitated by lymphatic and blood vessels. The • Mark Dawson cells that line these vessels (the endothelial cells) are the control pathogenesis of a range of haematological malignancies. • Marc Achen • Sarah-Jane Dawson points for changes to vessel structure and activity. The program is interested in understanding the key • Ricky Johnstone The program spans the breadth of basic science and The program provides broad opportunities for training of translational medicine with the goal of identifying novel role played by the non-malignant cells within the postgraduate students, postdoctoral fellows, pathology fellows and • Lev Kats therapies that will improve the outcome of patients with tumour microenvironment, which includes stromal clinically trained researchers in areas of basic scientific research, haematological cancers. cells, blood vascular endothelial cells, lymphatic translational research and molecular pathology. endothelial cells and immune cells.

Prostate Cancer Program https://www.petermac.org/research/programs/prostate-cancer -program Oncogenic Signalling and Growth Control Program Research Labs: Research in this program includes but is not limited to: https://www.petermac.org/research/programs/oncogenic-signalling-growth-controlResearch Labs: A key feature of oncogenic signalling is -program a requirement for cells to • Ygal Haupt • Which tumours are aggressive vs indolent and put men at high grow and proliferate, processes that are intimately linked to risk of progressing to aggressive disease? • Rick Pearson protein synthesis and the provision of metabolic substrates for • Gail Risbridger • What returns predict tumour progression • Grant McArthur: Molecular Oncology replication of cellular components. Specifically, increases in ribosomal assembly, mRNA translation and glycolysis are key • What treatments can prolong and improve patient survival? • Vihandha Wickramasinghe The Prostate Cancer program aims to answer downstream events in many of the most important pathways significant questions that arise at diagnosis and The group uses patient specimens and clinically relevant models of • Ygal Haupt involved in malignant transformation. It is increasingly during treatment of men with Prostate cancer. prostate cancer to provide practice changing outcomes to benefit recognised that tumour heterogeneity both between lesions and men with prostate cancer. within lesions in individual patients and the development of Despite being a fundamental part of life, we still lack The global effort to understand the molecular resistance, represent fundamental challenges to attainment of a clear understanding of how individual organs know drivers of cancer is now coming to fruition with the durable responses to targeted therapies. Unravelling the links how to grow to the right size and maintain this size. identification of specific genomic events that influence between oncogenic signalling and their influence on cell biology signalling through key oncogenic pathways. will be critical to designing new therapeutic approaches and improving patient outcomes.

7 CANCER RESEARCH PROGRAMS

Gastrointestinal Cancer Program https://www.petermac.org/research/programs/gastrointestinal-cancer-program

Research Labs: This Program has developed a world-class multi-disciplinary translational research program that responds to the needs of • Wayne Phillips patients by (i) addressing critical clinical questions related to • Rob Ramsay treatment and management of gastrointestinal cancer, (ii) exploring the cellular and molecular biology underlying the development and • Alex Boussioutas progression of gastrointestinal malignancies, and (iii) actively • Nicholas Clemons translating laboratory findings into the clinic.

The program has a focus on gastric, oesophageal, colorectal, and Focussing on clinical, preclinical, and basic science anal cancers, and has strong clinical links with a surgical research research across all cancers of the gastrointestinal team led by Professor Sandy Heriot and additional surgeons and tract (including oesophageal, gastric, colorectal and oncologists within the Victorian Comprehensive Cancer Centre anal cancers). alliance, offering extensive training opportunities for postgraduate students, postdoctoral fellows and clinicians in basic, translational, and/or clinical research.

Tumour Angiogenesis and Microenvironment Program https://www.petermac.org/research/programs/tumour-angiogenesis-microenvironment -program

Research Labs: The interaction of these cells types with tumour cells can either support or inhibit tumour progression. The spread of cancer to • Steven Stacker lymph nodes and distant organs is a critical aspect of cancer • Stephen Fox progression and is facilitated by lymphatic and blood vessels. The cells that line these vessels (the endothelial cells) are the control • Marc Achen points for changes to vessel structure and activity. The program is interested in understanding the key The program provides broad opportunities for training of role played by the non-malignant cells within the postgraduate students, postdoctoral fellows, pathology fellows and tumour microenvironment, which includes stromal clinically trained researchers in areas of basic scientific research, cells, blood vascular endothelial cells, lymphatic translational research and molecular pathology. endothelial cells and immune cells.

Prostate Cancer Program https://www.petermac.org/research/programs/prostate-cancer -program

Research Labs: Research in this program includes but is not limited to: Research Labs: A key feature of oncogenic signalling is a requirement for cells to • Ygal Haupt • Which tumours are aggressive vs indolent and put men at high grow and proliferate, processes that are intimately linked to risk of progressing to aggressive disease? • Rick Pearson protein synthesis and the provision of metabolic substrates for • Gail Risbridger • What returns predict tumour progression • Grant McArthur: Molecular Oncology replication of cellular components. Specifically, increases in ribosomal assembly, mRNA translation and glycolysis are key • What treatments can prolong and improve patient survival? • Vihandha Wickramasinghe The Prostate Cancer program aims to answer downstream events in many of the most important pathways significant questions that arise at diagnosis and The group uses patient specimens and clinically relevant models of • Ygal Haupt involved in malignant transformation. It is increasingly during treatment of men with Prostate cancer. prostate cancer to provide practice changing outcomes to benefit recognised that tumour heterogeneity both between lesions and men with prostate cancer. within lesions in individual patients and the development of Despite being a fundamental part of life, we still lack The global effort to understand the molecular resistance, represent fundamental challenges to attainment of a clear understanding of how individual organs know drivers of cancer is now coming to fruition with the durable responses to targeted therapies. Unravelling the links how to grow to the right size and maintain this size. identification of specific genomic events that influence between oncogenic signalling and their influence on cell biology signalling through key oncogenic pathways. will be critical to designing new therapeutic approaches and improving patient outcomes.

Peter MacCallum Cancer Centre 8 CANCER RESEARCH PROGRAMS

Computational Biology Program https://www.petermac.org/research/programs/organogenesis-cancer

Research Labs: Our research interests encompass: bioinformatics algorithm and methods development; computational cancer biology; • David Goode cancer evolution and genomics; software tool development; and • Tony Papenfuss personalised medicine. The program includes research laboratories, as well as the The Computational Biology Program uses Bioinformatics Consulting Core and the Research Computing Facility. mathematics, statistics and computing to generate Scientists come from a range of disciplines including biology, new discoveries in cancer. We develop new models, computer science, mathematics and statistics, as well as algorithms and software tools, and apply these to software engineering. Many researchers in the program hold joint make sense of cancer data. This includes whole appointment with other programs or institutes. genome, exome, transcriptome and epigenome sequencing data.

Cancer Metabolism Program https://www.petermac.org/research/programs/cancer-metabolism

Research Labs: Areas of interest in the program include understanding: • Kristin Brown • obesity and the metabolic syndrome increasing the risk of cancer • Louise Cheng • obesity driving tumour growth • Andrew Cox • redox balance in tumour development • Rick Pearson • nutrient availability and utilisation driving tumour growth • Tony Tiganis • metabolic heterogeneities in cancer The ability of tumour cells to reprogram key metabolic pathways to facilitate tumorigenesis • tumour metabolism altered to support cancer growth and and metastasis is now recognised as one of the spread hallmarks of cancer. • mechanisms by which oncogenic pathways reprogram tumour The Cancer Metabolism Program has been recently metabolism established at the Peter MacCallum Cancer Centre • alterations in tumour metabolism influencing the immune and aims to understand the influence of obesity response and metabolism on the development and growth of cancer. • alterations in immune cell metabolism influencing tumour growth

• tumour metabolism promoting therapy resistance • targeting tumour-specific metabolic vulnerabilities for cancer therapy

9 RESEARCH EDUCATION PROGRAM With strong links to local and international universities and research institutes, our research Computational Biology Program education program provides a training and support framework for the academic and professional development of our staff and students. https://www.petermac.org/research/programs/organogenesis-cancer Peter Mac is home to over 150 research students undertaking postgraduate and honours research programs. Most Research Labs: Our research interests encompass: bioinformatics algorithm students completing projects at Peter Mac are enrolled through The University of Melbourne. We also host students from and methods development; computational cancer biology; • David Goode all Universities throughout Australia and overseas. cancer evolution and genomics; software tool development; and • Tony Papenfuss personalised medicine. Our program provides all students with the opportunity to expand their research knowledge and skills, while also developing important transferable skills that will make an important contribution to their future career directions. The program includes research laboratories, as well as the The Computational Biology Program uses Bioinformatics Consulting Core and the Research Computing Facility. We provide a structured yet flexible program to meet the varied needs of our students. This research environment supports all students during the development of the important research and professional skills that will allow our mathematics, statistics and computing to generate Scientists come from a range of disciplines including biology, graduates to demonstrate their development as efficient researchers, and makes a significant contribution to improving new discoveries in cancer. We develop new models, computer science, mathematics and statistics, as well as the quality of research coming out of our Centre. algorithms and software tools, and apply these to software engineering. Many researchers in the program hold joint appointment with other programs or institutes. make sense of cancer data. This includes whole Sir Peter MacCallum Department of Oncology, The University of Melbourne genome, exome, transcriptome and epigenome sequencing data. The University of Melbourne’s Sir Peter MacCallum Peter Mac and the Sir Peter MacCallum Department of Department of Oncology is located within the Peter Oncology also provide research placements for medical MacCallum Cancer Centre. research programs, for international postgraduate students, for undergraduate students associated with The Sir Peter Mac Department brings to the university the the Summer Vacation Research Program, undergraduate strengths of world-class laboratory and clinical research work experience and undergraduate research projects conducted within a public cancer hospital, including: Cancer Metabolism Program undertaken in the laboratories. • the largest cancer research group in Australia, with https://www.petermac.org/research/programs/cancer-metabolism laboratory-based researchers and clinicians working Postgraduate research students based in clinical settings side-by-side; are supported by the Cancer Research Education program in addition to the support offered by their clinical service teams. Research Labs: Areas of interest in the program include understanding: • a strong academic program, driven by internationally • Kristin Brown • obesity and the metabolic syndrome increasing the risk of renowned laboratory and clinical researchers, with The co-location of research and research training capability cancer a strong focus on educating future generations of with a hospital dedicated to cancer treatment enables • Louise Cheng cancer researchers; researchers and clinicians to work side-by-side to make • obesity driving tumour growth significant contributions to basic research, translational • Andrew Cox • highly sophisticated equipment and technology, • redox balance in tumour development research and clinical trials for cancer. • Rick Pearson enabling complex research projects through access • nutrient availability and utilisation driving tumour growth to cutting-edge core research technology platforms The Peter Mac Research Education program formed the • Tony Tiganis basis of The University of Melbourne’s Comprehensive • metabolic heterogeneities in cancer • a cancer stream-based and holistic model of care Cancer PhD program, described in the following section. The ability of tumour cells to reprogram key where multi-disciplinary experts come together to metabolic pathways to facilitate tumorigenesis • tumour metabolism altered to support cancer growth and provide tailored treatment at all stages of a patient’s and metastasis is now recognised as one of the spread disease, across all common and rare cancer types. hallmarks of cancer. • mechanisms by which oncogenic pathways reprogram tumour The Cancer Metabolism Program has been recently metabolism established at the Peter MacCallum Cancer Centre • alterations in tumour metabolism influencing the immune and aims to understand the influence of obesity response and metabolism on the development and growth of cancer. • alterations in immune cell metabolism influencing tumour growth

• tumour metabolism promoting therapy resistance • targeting tumour-specific metabolic vulnerabilities for cancer therapy

Peter MacCallum Cancer Centre 10 COMPREHENSIVE CANCER PhD PROGRAM The Comprehensive Cancer PhD program (The University of Melbourne) supports the academic and professional development of students undertaking cancer-related research within the Victorian Comprehensive Cancer Centre (VCCC) Alliance.

This innovative and integrated program aims to produce The program includes: graduates ready to conduct world-class cancer research 1. Research skills development, including mastery of and set them on a path to a broad range of career options. core technologies, cancer-specific seminars and The Comprehensive Cancer PhD (CCPhD) Program is presentations and critical analysis through exposure to designed to complement existing PhD activities by journal clubs. providing eligible students with opportunities to broaden 2. Professional and career development, including the scope of their research knowledge, professional generic and transferrable skills, mentoring, networking, development and career training, and to develop research leadership, career opportunities, internships and and professional skills that will help students to fulfill their placements. career ambitions. 3. Communication skills development, including thesis and The Comprehensive Cancer PhD builds on established journal writing skills, and oral or poster presentations conventional training for cancer research students skills. providing a coordinated program of skills, research and career training in addition to usual PhD activities. 4. Optional internships/placements tailored to the student’s interests and relevance to their PhD. Tapping into the depth and breadth of knowledge and experience of the VCCC alliance partners, the program Examples of student activities in this program: provides a unique opportunity for multidisciplinary cancer- • Annual Student Symposium related PhD candidates to experience clinical and research activities across the alliance. • Annual Debate The program is managed by the Sir Peter MacCallum • Thesis Bootcamp Department of Oncology (University of Melbourne), and is • Annual Chat with a Nobel Laureate based on the gold-standard postgraduate program offered by Peter Mac. • Topics in Cancer Seminar program, with recent topic themes including: All students engaged in postgraduate research studies at Cancer Immunotherapy; Peter Mac are enrolled in the CCPhD program, regardless of which university they are enrolled through. Oncogenes and Tumour Suppression; Pillars of Cancer Care Cancer Genetics and Genomics - Workshops, including presentation skills, communication skills, candidature management, CV preparation.

For further information, email: [email protected]

The Comprehensive Cancer PhD Program is supported by academic partner the University of Melbourne, Peter MacCallum Cancer Centre and the Victorian Comprehensive Cancer Centre alliance

11 BECOMING A STUDENT AT PETER MAC

We provide a world-class research education program at a leading Australian cancer research institution for students from The University of Melbourne and other national and international universities. There are two general stages in preparing to become a Honours students student in our postgraduate and honours programs. Each year we accept students from biomedical science and Students must: science programs to undertake one-year, full time Honours 1. Find a project and supervisor for their research projects in cancer-related biomedical research. program, and Students undertake all of their scientific research work on 2. Meet the University degree eligibility and entry site at Peter Mac, while undertaking their course work at the university department through which they are enrolled. requirements. Our honours students come to us with a range of majors Postgraduate students and backgrounds including biochemistry, chemistry, biomedical science, immunology, cell biology, medicine, Applicants for postgraduate student positions at Peter Mac pharmacology, molecular biology, pathology, physiology, enrol through a university program that approves your anatomy and other similar subjects. project placement at Peter Mac. You must therefore satisfy Most of our Honours students are enrolled at The the minimum entry requirements at the university through University of Melbourne through departments of the which you plan to enrol. Faculty of Medicine, Dentistry and Health Sciences, Entry to the Peter Mac postgraduate program is based on such as: Biochemistry & Molecular Biology, Pathology, the availability of projects, student suitability and academic Microbiology & Immunology, Anatomy & Cell Biology and background. Pharmacology. To undertake a postgraduate project at Peter Mac, students Students who have completed their undergraduate degree need to: at another university in Australia or overseas are also encouraged to contact us directly for further information • Demonstrate a genuine interest in biomedical on how to apply. research. Students interested in undertaking an Honours project at • Be happy to conduct your research candidature full Peter Mac need to: time off-campus at Peter Mac. • Demonstrate a genuine interest in biomedical • Look through the available project summaries and research. contact the project supervisor directly by email. • Ensure their university/department approves them • Discuss your interest in the project with the conducting their research project full time off-campus supervisor. at Peter Mac. • Meet with potential supervisors at Peter Mac to • Look through the available project summaries and discuss the project, your interests, visit the lab and contact the project supervisor directly by email. meet others in the research group. At this meeting, supervisors will also want to view your academic • Discuss your interest in the project with the supervisor. record. International students will ‘meet’ supervisors • Meet with potential supervisors at Peter Mac to discuss via skype or similar. the project, your interests, visit the lab and meet others • Meet univeristy eligibility requirements for in the research group. At this meeting, supervisors will postgraudate degree candidature. also want to view your academic record. • Apply for candidature at The University of Melbourne • Apply for candidature at the University, meeting the or at an equivalent university when supervisor and university’s application and eligibility requirements. project are confirmed. University of Melbourne students enrol with The Sir Peter MacCallum Assistance in the application process Department of Oncology, through the Faculty of Further information about the postgraduate and Medicine, Dentistry and Health Sciences. honours projects, supervisor contact details and the • Apply for a postgraduate scholarship. Note the application process is available online at: different deadlines that apply to different scholarships, different universities, and for local versus international www.petermac.org/education/research- scholarships. education Peter Mac staff will work with students to facilitate these For application assistance, contact: processes. [email protected] Applications for candidature/scholarships for all universities are online processes, requiring a leter of supprot from the proposed supervisor.

12 WHERE DO OUR STUDENTS COME FROM TO STUDY AT PETER MAC?

We host students from countries and universities all over the world to undertake their research studies at Peter Mac. Our mulitdisciplinary and multicultural student cohort is at the heart of our research excellence.

WHERE DO ARE OUR GRADUATES GO AFTER THEY COMPLETE THEIR DEGREES? Our graduates have taken up research positions across the world at leading research institutes and universities as post-doctoral researchers and academic leaders, including:

USA: Memorial Sloan Kettering Cancer Center, Dana- EUROPE: Research Institute of Molecular Pathology, Farber Cancer Center, MD Anderson Cancer Center, Austria; University of Zurich, Switzerland; NKI, Amsterdam; Stanford University, Harvard University, University of Max Planck Institute of Immunobiology and Epigenetics, California (LA, Irvine, SF), St Jude’s Children’s Research Frieberg, Germany; Ludwig-Maximilians Universität Hospital, University of Pennsylvania, Mount Sinai Hospital, München, Germany; Institute for Molecular Medicine, University of Pittsburgh, Medical College of Wisconsin Finland; Karolinska Institute, Sweden; Stockholm Cancer Centre, University of Texas Health Science Center, University, Sweden; Gustav Roussy, France; University Brigham and Women’s Hospital, Boston; British Oregon of Paris Sud XI, France; Antoni van Leeuwenhoek, Health and Science University, NYU School of Medicine, Netherlands, Colorado Cancer Centre, John Hopkins School of Medicine, Roswell Park Cancer Institute; Northwestern University; ASIA: Center for Genome Integrity, Institute for Basic Columbia University. Science, Korea; Nanyang University Hospital, Singapore. CANADA: University of Toronto, British Columbia Cancer Agency, Vancouver. Our graduates have taken up research positions across Australia and the world at leading UK: Cambridge University; Cancer Research UK; University College London; University of Dundee; The Beatson Institute companies including: for Cancer Research, Glasgow; Nottingham University Amgen, Roche, Pionyr Immunotherapies, Comugen Hospitals NHS Trust; St Andrews University Edinburgh; Ltd, GSK, Seres Therapeutics, Genesearch, Geneworks, Sanger EBI; Medical Research Council; University of Australian Department of Health (PBS), Davies Collison Birmingham. Cave Intellectual Property, Merck, QIAGEN.

Peter MacCallum Cancer Centre 13 WHY STUDY AT PETER MAC? WORDS FROM OUR PAST RESEARCH STUDENTS

Collaborative interaction with national and international peers is a lynchpin of any vibrant program. Peter Mac is continually seeking to work with the best worldwide and the world’s best are increasingly seeking out Peter Mac researchers to interact with. In speaking to past research students, it is immediately evident that the two factors most strongly influencing their decision to join and stay at Peter Mac are firstly, the opportunity to be mentored by a strong and collegiate group of senior researchers and secondly, the well-established research infrastructure that enabled them to perform virtually any type of experiment they required at affordable cost. This is a strong vindication of our strategy of identifying, seeding and supporting the growth of an enabling environment, both in terms of talented senior personnel and a first-class research infrastructure.

“I have been incredibly fortunate to be part of a dynamic and supportive research group at The National Centre for Infections in Cancer at Peter Mac. My inspiring PhD supervisors Prof Karin Thursky and Prof Monica Slavin have taught me to think beyond the hospitals walls, to collaborate across disciplines and to translate my research into practice.”

Gabrielle’s research encompasses three domains: risk prediction, health-services utilisation and implementation. Her vision is to lead national knowledge translation studies to improve the management of infections in cancer with a focus on standardising practice, reducing unwarranted variation and improving efficiencies within the healthcare system. Results of Gabrielle’s PhD have already been implemented across Victoria and have resulted in significant reductions in hospital length of stay for children with cancer and febrile neutropenia (FN).

Dr. Gabrielle Haeusler: Infectious Diseases Physician and Clincial Researcher, Peter MacCallum Cancer Centre. Recipient: 2018 Premier’s Award for Health Service Research; 2019 Chancellor’s Award, The University of Melbourne; 2019 Peter Mac Postgraduate Research Medal.

“Doing a PhD at Peter Mac surrounded by a critical mass of world-class cancer researchers is invaluable experience for any young investigator and certainly was for me. Apart from learning an array of scientific techniques, it honed my ability to critically evaluate data, to present my own data verbally and in writing, and allowed me to get my first independent funding (a CJ Martin Fellowship) to undertake postdoctoral training at the British Columbia Cancer Agency.”

Arun is a clinician-researcher with a focus on urological cancers and especially prostate cancer. He has a key role in early- and late-phase clinical trials in prostate cancer, including investigator-sponsored studies, and leads a lab team focused on characterising circulating blood-based biomarkers in advanced prostate cancer. HIs My work is supported by research grants and fellowships from NHMRC, Victorian Cancer Agency and other funding bodies including industry partners. He is co-PI of the Upfront-PSMA Movember/Cancer Australia Prostate Cancer Research Alliance.

A/Prof. Arun Azad: Medical Oncologist and Clinician Researcher, Peter MacCallum Cancer Centre. “I was attracted by Peter Mac’s reputation as a holistic cancer centre with everyone striving towards one goal. In this supportive and collaborative environment I developed my potential towards making a significant contribution to the field of cancer research.” Nimali completed a postdoctoral position at Stanford School of Medicine. She is now a Clinical Scientist at Genentech/Roche working in Product Development Oncology, responsible for developing and executing the late stage (Phase II – IIIA) clinical strategies and plans, to help deliver novel therapies that provide significant improvement to patient health. Her goal is to translate promising, innovative scientific breakthroughs to global health that impacts patients.

Dr. Nimali Withana, Clinical Scientist, Genentech/Roche, USA

14 “Undertaking a PhD at the Peter MacCallum Cancer Centre was critical to the development of my career. Being immersed in an institute dedicated to cancer research gave me a wide and diverse exposure to different aspects of cancer biology, enabling me to tap in to different areas of expertise whenever I needed it. The PhD education program and interaction with scientists across the institute (especially other PhD students) provided me with a solid foundation across multiple areas of cancer biology from cancer genetics, metastasis, immunology and more.”

Nick’s research interests in upper GI cancers were developed during research fellowships in the Surgical Oncology Research Lab at Peter Mac and the MRC Cancer Cell Unit at the University of Cambridge. Throughout his career, collaboration with clinicians (especially surgical oncologists, medical oncologists and gastroenterologists) has been critical to his research by enhancing the relevance of his work to the most critical issues facing patients with oesophageal cancer. Nick’s research group focusses on understanding the tumourigenic process in oesophageal cancer and they use this knowledge to investigate opportunities to improve clinical management of this disease, including the identification of new therapeutic approaches.

Dr. Nicholas Clemons: Head, Tumourigenesis & Cancer Therapeutics Laboratory, Peter MacCallum Cancer Centre; Senior Honorary Fellow in the Sir Peter MacCallum Department of Oncology at The University of Melbourne.

“I was very fortunate to do my PhD doing something I was really passionate about – cancer immunotherapy. I had a wonderful time during my PhD at Peter Mac, not only because it is a great place to work in with all the amazing people and staff, but also because of all the opportunities I got as a PhD student. Peter Mac always brings in the best scientists from various fields in cancer research, and all those seminars definitely helped me learn so much about exciting current research outside of my own. All the training I had at Peter Mac definitely has helped equip me with important skills that I need here as a scientist, not only laboratory skills but also communication and presentation skills.”

Sherly’s PhD My research focused on T cell immunotherapy, in particular chimeric antigen receptor (CAR) T cell therapy which involves genetic engineering of T cells to redirect their specificity to target tumour antigen(s). Sherly made the most of the opportunties for personal development thorughout her PhD; she developed from being a timid first year student into to a mature confident scientist in her final year, presenting at international conferences and labs in the US. After these conferences and lab visits, she was offered a few post-doctoral positions in a number of institutes in Canada and the US, which then led her to her current role as a post-doctoral scientist at the University of Pennsylvania in Philadelphia.

Dr. Sherly Mardiana: Postdoctoral Scientist, University of Pennsylvania, USA.

“Attending a Peter Mac Student Open Day in the 3rd year of my undergarudate degree, I was struck by the enthusiasm and the collaborative environment at the open day, and on subsequent visits to the labs. More so than other institutes that I’d visited and work at, I didn’t really notice a clear distinction between RAs, students and post-docs. I felt that everybody had an opportunity to contribute to the discussion around the experiments.”

Don completed his Honours year at Peter Mac in 2010, following which he worked in various RA roles in the Oncologenic Signalling and Growth Control Program before commencing his PhD in 2014. He remained at Peter Mac throughout these stages of his early research career because he enjoyed the excellence of the research environment and facilities, and he was learning a lot from the people at Peter Mac. After completing his PhD, he commenced a postdoctoral position at the Karolinska Institute, Sweden, in June 2018.

Dr. Don Cameron: Postdoctoral Scientist, Karolinska Institute, Sweden

Peter MacCallum Cancer Centre 15 AVAILABLE PROJECTS BY RESEARCH GROUP

BEAVIS, PAUL therapeutic responses. The potential of radiomics has shown in several cancer types including breast, brain, head and neck, and lung. With the advancement in deep TUMOUR IMMUNOLOGY PROGRAM learning methods and availability of high computational https://www.petermac.org/research/labs/paul-beavis power, deep learning methods are successfully being used in radiomics. In this project, we aim to develop deep Enhancing lymphocyte trafficking to improve the learning models based on convolutional neural networks to Immunotherapy of Cancer quantify radiological features from pre- and post-treatment MRI/PET images to predict disease free survival (DFS) and Supervisors: Dr. Paul Beavis, Dr. Imran House, Prof. Phil Darcy loco-regional control (LRC) in cancer patients after therapy. Initially the project will focus on breast and cervical cancer Recent immunotherapy successes in the clinic have patients. highlighted the potential of harnessing the immune system to target cancer. The number of tumour-infiltrating During this project, the student will develop software to, lymphocytes (TILs) positively correlates with disease 1) automatically delineate the tumour outcome in cancer patients treated with standard chemotherapy or checkpoint inhibitor immunotherapy. 2) extract features from multiple image types In patients with low TILs, a group which constitutes 3) and automatically predict survival outcomes using pre- the majority of cancer patients, immunotherapy with treatment images checkpoint inhibitors (e.g. anti-PD-1) has been largely ineffective to date, underlining the need to develop This project will be suitable for a student with a strategies to increase the recruitment of TILs. Trafficking background in mathematics or computer science or of immune cells, including T cells, is modulated by a engineering. Prior experience in computational biology or complex network of chemokine: chemokine receptor image analysis would be beneficial. interactions. Chemokines interact with their respective Key Words: Deep Learning; Machine Learning; Radiomics; chemokine receptors and binding results in the activation MRI; Bioinformatics; Gynaecological Cancers; Breast of intracellular signalling pathways which result in the Cancer. migration of the target cells towards the source of the chemokine. Target Students: PhD/postgraduate. This project will employ state-of-the art technology to For more information about this project contact: identify novel regulators of the key chemokines involved Dr. Kaushalya Amarasinghe in this process and test the potential of targeting these to [email protected] enhance lymphocyte infiltration into tumours and therefore increase the efficacy of checkpoint immunotherapy and chimeric antigen receptor (CAR) T cells. This approach has high translational potential and has the capacity to BOUSSIOUTAS, ALEX significantly enhance the effectiveness of Immunotherapy GASTROINTESTINAL CANCER PROGRAM in cancer. Role of the tumour microenvironment in gastric cancer Key Words: Breast Cancers, Cellular Immunology, Genetic Immunology, Immunotherapy, Sarcoma, Skin Cancers (incl. Supervisors: Prof. Alex Boussioutas, Dr. Rita Busuttil Melanoma), Solid Tumours, Tumour Immunology. Gastric cancer (GC) is the fourth most common cancer Target Students: PhD/postgraduate, Honours. globally and 7th in incidence in Australia. It has a poor survival rate which can be attributed to the advanced stage For more information about this project contact: at diagnosis in most patients. The molecular and cellular Dr. Paul Beavis [email protected] mechanisms underlying the development of GC are not well described. Traditionally cancer research involved studying the cancer cell itself. More recently, there has BIOINFORMATICS CONSULTING CORE been growing interest in studying the normal cells and molecules which surround the cancer cell. This tumor https://www.petermac.org/research/core-facilities/ microenvironment consists of a variety of stromal cell bioinformatics types including cells such as fibroblasts. It is believed that the dynamic communication between tumor cells and the Deep learning methods for fast and accurate cancer surrounding cell types may play a major role in cancer prognostication using radiological images initiation, progression and establishment of metastatic Supervisors: Prof. Saman K. Halgamuge (The University of disease. Melbourne), Dr. Jason Li (Peter Mac) and Dr. Kaushalya C. The aim of this project is to investigate tumor-stromal Amarasinghe (Peter Mac) interactions in gastric cancer utilizing established and ‘Radiomics’, the field of extracting quantitative features primary cell lines. Once the molecular pathways by which from medical images to explain radiological phenotypes, a tumor cell progresses has been elucidated it is possible can be used to discriminate disease forms and to predict that these processes could be exploited in the development of novel therapeutics. Our previous genomic experiments Peter MacCallum Cancer Centre 16 AVAILABLE PROJECTS BY RESEARCH GROUP have provided a number of exciting candidate genes that Key Words: Cancer Cell Biology, Gastric Cancer; Cancer may be involved in this interaction. This is novel research Genetics; Genomics; Cancer Prevention, Organoid, Molecular that may have a major benefit to our understanding of Biomarkers, Upper Gastrointestinal Cancers. cancer and improve patient outcomes. Target Students: PhD/postgraduate, Honours. Key Words: Gastric Cancer; Tumour Microenvironment; Cancer Diagnosis; Cancer Genetics; Genomics; Upper Gastrointestinal Cancers. Investigating the innante and adaptive immune response in gastric cancer Target Students: PhD/postgraduate, Honours. Supervisors: Prof. Alex Boussioutas, Dr. Rita Busutti Cancer is a disease involving complex interactions of Twist as a regulator of EMT in gastric cancer and its role the tumor cell along with a multitude of other cell types, in invasion including immune cells, which comprise the tumor Supervisors: Prof. Alex Boussioutas, Dr. Rita Busuttil microenvironment. It is this cross-talk that promotes cancer growth, invasion and metastasis. The immune Gastric cancer (GC) is often diagnosed at advanced system consists of an integrated system with two major stages, giving patients a 5-year survival of less than 20%. components: the innate and adaptive response systems. Advanced stage GC is directly correlated with increased Our laboratory is interested in examining the role of immune local invasion of the cancer through the gastric wall and, at system in the context of gastric cancer (GC). We have more advanced stages into adjacent structures Epithelial individually characterized the spatial distribution of cells Mesenchymal Transition (EMT) is one mechanism which comprising both the innate and adaptive immune system. has been proposed as a modulator of invasion in GC as well as other cancer types. This project aims to integrate these data to help elucidate the degree of cross talk between the two systems and to validate This project seeks to expand on previous work in our the findings using in vitro and in vivo model systems with the laboratory exploring the role of TWIST, a master regulator ultimate aim of developing novel therapeutic strategies for of EMT, in gastric cancer. We have previously shown that treating GC. TWIST is more highly expressed at the invasive front of the tumor compared to its core indicating that EMT Key Words: Cancer Cell Biology, Cancer Immunology, is occurring in this area. It is conceivable that reducing Immunotherapy, Innate Immunity, Terapeutics, Upper TWIST expression could be used as a means to decrease Gastrointestinal Cancers. the invasive capacity of a cancer. This project will aim Target Students: PhD/postgraduate, Honours. to further explore the role of TWIST in the invasion of GC and its potential utility as a therapeutic target. A broad For more information about these projects contact: range of techniques including bioinformatics, cell culture, Prof. Alex Boussioutas [email protected] shRNA lentivirus mediated gene knockdown, and molecular biology will be applied. Dr. Rita Busuttil [email protected] Key Words: Gastric Cancer; Cancer Diagnosis; Cancer Genetics; Genomics; Upper Gastrointestinal Cancers. Target Students: PhD/postgraduate, Honours. BOWTELL, DAVID CANCER GENETICS AND GENOMICS PROGRAM Functional characterisation of genes involved in https://www.petermac.org/research/labs/david-bowtell progression of gastric cancer Analysis of heterogeneity and chemotherapy resistance in Supervisors: Prof. Alex Boussioutas, Dr. Rita Busutti ovarian cancer Gastric cancer (GC) is the fourth most common cancer Supervisors: Dr. Liz Christie, Prof. David Bowtell globally. It has defined premalignant stages and progresses A majority of women with high-grade serous ovarian cancer through Intestinal Metaplasia (IM) in the majority of respond well to primary treatment but eventually develop cases. GC is diagnosed at advanced stage resulting in drug resistance. We are currently performing whole genome poor prognosis. Part of this is due to no means to identify and single cell RNA sequencing of tumour samples collected and screen persons at risk of GC. Relatively little is from patients at recurrence or autopsy to further our known about the key genetic events leading to IM. Our understanding of how tumours evolve to become resistant to laboratory is currently in the process of completing the first chemotherapy. comprehensive analysis of IM in the world and we have identified a number of candidate genes which are likely This project will involve analysis of whole genome and to be involved in the progression of IM to GC. These could single cell RNA sequence data to (1) identify resistance potentially be used to reliably predict the progression to mechanisms, (2) understand their heterogeneity within and GC in humans enabling clinical stratification of individuals between patients, and (3) examine how tumour subclones into high-risk groups. This project would involve functional interact and evolve over time in response to chemotherapy. validation of these candidates using cell culture and A broad range of techniques including bioinformatics, cell organoid model systems culture and molecular biology will be applied. 17 AVAILABLE PROJECTS BY RESEARCH GROUP

Key words: Bioinformatics, Cancre Cell Biology, Cancer Key words: Cancer Cell Biology, Cancer Genetics, Genomics, Genetics, Genomics, Gynaecological Cancers, Molecualr Ovarian Cancer, Molecular Biomarkers, Tumour Immunology Biomarkers, Therapeutics Target Students: PhD/postgraduate Target Students: Masters, PhD/postgraduate For more information about this project contact: For more information about this project contact: Dr. Dale Garsed [email protected] Dr. Liz Christie [email protected] Prof. David Bowtell [email protected] Prof. David Bowtell [email protected]

Examining cell fitness in chemotherapy resistant ovarian BRITT, KARA cancer CANCER GENETICS AND GENOMICS PROGRAM Supervisors: Dr. Liz Christie, Prof. David Bowtell https://www.petermac.org/research/labs/kara-britt Despite aggressive surgery and chemotherapy, a majority Developing breast cancer preventatives by mimicking of women with high-grade serous ovarian cancer develop parity’s protective role drug resistance. We have identified a number of acquired drug resistance mechanisms, including chromosomal Supervisor: Dr. Kara Britt rearrangements that lead to overexpression of the Women who have children (parous) have a reduced risk multidrug resistance pump P-glycoprotein. P-glycoprotein of breast cancer and this protection is strongest for those requires ATP to efflux drugs; therefore, its overexpression bearing children early. Women having children later in life places an energetic penalty on cells with the mutation. are not protected against breast cancer, but instead at The aim of this project is to determine if there is a fitness an increased risk. We have developed a mouse model to disadvantage to cells with P-glycoprotein overexpression, determine the role of mammary stem cells and stromal and to determine whether this can be exploited to fibroblasts in parity-induced protection and will now test overcome drug resistance. therapies aimed at modulating these cells. Key words: Cancer Cell Biology, Gynaecological Cancers, Finding a therapy for triple negative breast cancer patients Therapeutics Supervisors: Dr. Kara Britt, Prof. Robin Anderson, Prof. Kelly Target Students: PhD/postgraduate, Honours Phillips For more information about this project contact: Triple negative breast cancers are a poor prognosis breast cancer with limited therapeutic options as they do not Dr. Liz Christie [email protected] express estrogen receptors, progesterone receptors or Her2. Prof. David Bowtell [email protected] Recent clinical studies have shown that women who have triple negative breast cancers, but also express the alternate estrogen receptor, ERB respond well to Tamoxifen. We Genomic determinants of long-term survival in ovarian will use our mouse model of triple negative breast cancer, cancer engineered to express ERB, to determine how Tamoxifen Supervisors: Prof. David Bowtell, Dr. Dale Garsed, Dr. exerts is benefits to these patients. This project will involve Jessica Beach RNA sequencing of tumours.

High-grade serous ovarian cancer is an aggressive disease The role of the immune system in early breast cancer in which only ~30% of women survive 5 years or more. Supervisors: Dr. Kara Britt, Prof. Phil Darcy Despite a poor prognosis, a subset of patients are highly responsive to chemotherapy, and some become long-term Breast cancer is not considered immunogenic, as its survivors (>10 years survival). This spectrum of treatment incidence is not increased in immune suppressed patients responses suggests fundamental differences in tumour (transplant patients and HIV patients). However, irrefutable biology that are not yet understood. In collaboration with data now show that the immune cell infiltrate of a breast the Australian Ovarian Cancer Study, our laboratory cancer affects its growth and metastasis. Only limited data is currently performing whole-genome sequencing, exist on the role of immune cells in the early stages of BCa. transcriptome sequencing and immune profiling of high- This project will determine whether immune changes occur grade serous ovarian cancer in long-term survivors. We early in the tumorigenic process of and whether this can be have identified a number of candidate genomic alterations treated with immunotherapy to inhibit cancer development. that may be associated with exceptional outcomes. Key Words: Breast Cancers, Cancer Cell Biology, This project will involve verification of candidates using Immunotherapy, Tumour Immunology. DNA sequencing, and functional validation using pre- Target Students: PhD/postgraduate. clinical models of ovarian cancer. Students will gain experience in human tissue culture, tumour biology and For more information about these projects contact: immunology, molecular biology techniques, genomics and Dr. Kara Britt [email protected] bioinformatics.

Peter MacCallum Cancer Centre 18 AVAILABLE PROJECTS BY RESEARCH GROUP

BROWN, KRISTIN for cancer therapy. Although most work has focused on the Akt kinase family as major downstream effectors of PI3K, CANCER THERAPEUTICS PROGRAM, & the closely related serum- and glucocorticoid-regulated kinase (SGK) family of serine/threonine kinases has by CANCER METABOLISM PROGRAM comparison received little attention. https://www.petermac.org/research/labs/kristin-brown Recently, SGK1 has been shown to play a critical role Fueling chemotherapy resistance in triple-negative in driving the expansion of tumour cells and promoting breast cancer resistance to conventional chemotherapy and targeted therapy agents. However, the molecular mechanisms Supervisor: Dr. Kristin Brown underlying the oncogenic activities of SGK1 are poorly Triple-negative breast cancer (TNBC) is a molecularly characterised. In this project, we will identify SGK1 heterogeneous group of diseases defined by the lack of substrates and interacting proteins using the proximity- estrogen receptor (ER), progesterone receptor (PR) and dependent biotin identification (BioID) method. Students absence of human epidermal growth factor receptor-2 will gain experience in mammalian cell culture and (HER2) amplification. Consequently, TNBCs are impervious proteomics (mass spectrometry) techniques. Targets to therapies commonly used in other breast cancer identified in the BioID screen will be validated using a subtypes and treatment options are largely limited to variety of biochemical and molecular biology techniques. conventional chemotherapy agents. Approximately 30% of Key Words: Breast Cancers, Cancer Therapy, Molecular TNBC patients respond to chemotherapy. Unfortunately, Biomarkers, Molecular Targets. the long-term prognosis for the majority of patients with residual disease after chemotherapy is poor. Target Students: PhD/postgraduate, Honours. Identification of novel and actionable strategies to sensitize For more information about these projects contact: cancer cells to chemotherapy would represent a major Dr. Kristin Brown [email protected] advance for the management of TNBC. Cancer cells exhibit dramatic alterations in cell metabolism, which support cell growth, proliferation and survival. Indeed, metabolic Cutting off the Fuel Supply to Starve Cancer: Identifying reprogramming is a recognized hallmark of cancer induced metabolic vulnerabilities in cancer by numerous genetic or epigenetic alterations. Our recent studies suggest that reprogramming of cellular metabolism Supervisors: Dr. Kristin Brown, Dr. Andrew Cox is also a component of the highly coordinated response to A universal characteristic of all cancer cells is the chemotherapy exposure. The aims of this project will be to: reprogramming of cell metabolism to provide the energy 1) identify adaptive metabolic reprograming events and building blocks necessary to support proliferation and triggered upon chemotherapy exposure, and survival. Reprogramming of cell metabolism occurs as a consequence of oncogenic mutations and renders cancer 2) identify novel therapeutic approaches to exploit adaptive cells dependent on a unique set of nutrients. It is now metabolic reprogramming events and sensitize TNBC cells widely recognized that the altered metabolic activity of to chemotherapy. cancer cells provides a window of opportunity to develop This research will lead to the identification of critical tumour-specific anticancer therapies. mechanisms driving chemotherapy resistance in TNBC and Using transcriptomic and metabolomic approaches, the establish combination therapy strategies with potential to aims of this project will be to: (1) compare and contrast have a major impact on patient survival. Students will gain metabolic reprogramming induced by well-described experience in mammalian cell culture, molecular biology oncogenes; (2) compare and contrast the nutrient techniques, metabolomics and stable-isotope labelling requirements of cancer cells dependent on well-described techniques. oncogenes and (3) identify and validate key metabolic Key Words: Breast Cancers, Cancer Therapy, Molecular vulnerabilities that can be targeted for the preclinical Biomarkers, Molecular Targets. development of novel anticancer strategies. Students will gain experience in mammalian cell culture, molecular Target Students: PhD/postgraduate, Honours. biology techniques, metabolomics and stable-isotope labelling techniques. Unravelling the oncogenic activities of serum- and Key Words: Breast Cancers, Cancer Therapy, Molecular glucocorticoid-regulated kinase 1 (SGK1) Biomarkers, Molecular Targets. Supervisor: Dr. Kristin Brown Target Students: PhD/postgraduate, Honours. The phosphoinositide 3-kinase (PI3K) pathway is a master For more information about this project contact: regulator of numerous cellular phenotypes associated with Dr. Kristin Brown [email protected] cancer including cell survival, proliferation, growth, altered metabolism and malignant transformation. Deregulation Dr. Andrew Cox [email protected] of the PI3K pathway is implicated in virtually all human cancers and the pathway has been aggressively targeted

19 AVAILABLE PROJECTS BY RESEARCH GROUP

CHENG, LOUISE How does amino acid metabolism affect tumour growth? ORGANOGENESIS AND CANCER PROGRAM, & Supervisors: Dr. Francesca Froldi, Dr. Louise Cheng CANCER METABOLISM PROGRAM The effect of diet on tumour growth is hotly debated but poorly characterized. Due to the heterogeneous nature of the tumours, https://www.petermac.org/research/labs/louise-cheng dietary studies in patients with varied genetic background often led to inconclusive outcome. Dedifferentiation is a cellular How do tumours grow at the expense of other tissues? process by which a partially or terminally differentiated cell Supervisors: Dr. Francesca Froldi, Dr. Louise Cheng reverts to a less differentiated, more multipotent state. The bidirectional conversion between differentiated cells and Cancer cells are known to drive altered metabolic circuits to stem cells often underlies carcinogenesis. Cancer such as meet the bioenergetic and biosynthetic demands of increased glioblastoma, the most aggressive subtype of the gliomas are cell growth and proliferation. Under nutrient restriction, when thought to originate from terminally differentiated cortical growth of most organs shut down, cancer cells can bypass astrocytes and neurons. Similarly, through expressing the right these brakes imposed on cellular growth, thus gaining a combination of transcription factors, non-cancer stem cells can growth advantage under these conditions. Furthermore, also convert to highly proliferative cancer stem cells found in during calchexia, which causes more than one third of cancer intestinal tumours. death, tumour derived factors can also induce the break down of fat and skeletal muscles, in order to generate metabolic Using a combination of genetics, metabolic and genomic intermediates necessary for the preferential tumour growth. techniques, the student will address the knowledge gap of how The signalling between tumours and other tissues is highly diet, in particular amino acid metabolism, impacts on cellular complex, and the adaptations that allow cancer cells to dedifferentiation, and tumour growth. These studies will allow preferentially activate growth are largely unknown. us to quickly and systematically identify tumour metabolic dependencies, and shed light on important metabolic targets, The student will: utilise a brain tumour model to study how which can be assessed in other stem cell and tumour settings. tumour cells communicate with other tissues to gain a growth advantage; and utilise Drosophila genetics, transplantation The student will use a combination of Drosophila genetics, assays, confocal microscopy, FACS analysis and molecular confocal microscopy, FACS analysis and molecular biology techniques to address this question. techniques to address this question. Key Words: Cancer Cell Biology, Cell Metabolism, Key Words: Cancer Cell Biology, Cell Metabolism, Differentiation, Molecular Imaging, Stem Cells. Differentiation, Molecular Imaging, Stem Cells. Target Students: PhD/postgrduate, Honours. Target Students: Honours.

Identification of factors mediating dedifferentiation in How does nutrition affect stem cell proliferation? regeneration Supervisors: Dr. Louise Cheng, Dr. Francesca Froldi, Dr. Christen Supervisors: Dr. Louise Cheng, Dr. Patricia Jusef Mirth (Monash) Dedifferentiation is a fundamental process, which allows The evolutionary size of animals and plants is determined by post-mitotic (non-dividing, mature) cells to revert to a stem cell intrinsic regulation and constrained by nutrient availability, cell-like state. It is an important mechanism, which allows and brain size is perhaps the most profound example of this. mature cells to re-enter the cell cycle to generate additional Understanding at the molecular level how stem cells respond to stem cells, and the regulation of this process has important nutrients will provide foundation for the understanding of how implications for regenerative medicine, where it is not well nutrient availability impacts on size and growth in multicellular understood how stem cells can be activated upon injury (in organisms. Once thought to be a mere consequence of the order to carry out repair). Deregulation of dedifferentiation state of a cell, metabolism is now known to play a pivotal role in also has important implications for tumour formation, as dictating whether a cell proliferates, differentiates or remains generation of ectopic stem cells can cause uncontrolled quiescent. proliferation and cancer. This project will investigate how metabolic rewiring operates We have so far identified a number of transcription factors in the neural stem cells using Drosophila as a model organism; important for dedifferentiation in the developing Drosophila and more specifically how metabolic pathways can influence CNS, and in this project, the student will test the idea that body size, organ shape and whether neural stem cell these dedifferentiation regulators are also involved in neural proliferates or remain quiescent. The techniques will involve: regeneration using the Drosophila adult CNS. The candidate immunohistochemistry, tissue microdissection, metabolite genes identified in the Drosophila will then be tested for their measurements. significance in a neural regeneration model mediated by Key Words: Cell Growth, Cell Signalling, Stem Cells. Muller glia stem cells in the zebrafish vertebrate. Target Students: PhD/postgraduate. Key Words: Cancer Cell Biology, Differentiation, Stem Cells For more information about these projects contact: Target Students: PhD/postgraduate, Honours. Dr. Louise Cheng [email protected]

Peter MacCallum Cancer Centre 20 AVAILABLE PROJECTS BY RESEARCH GROUP

CLEMONS, NICHOLAS of regeneration and cancer. The students will use a combination of innovative GASTROINTESTINAL CANCER PROGRAM biochemical, genetic and imaging approaches in zebrafish to identify the metabolic dependencies of tissue growth https://www.petermac.org/research/labs/nicholas-clemons during regeneration and cancer. Supervisor: Dr. Nicholas Clemons Key Words: Cancer Cell Biology, Cancer Therapy, Cell The Clemons Laboratory incorporates fundamental cancer Growth, Cell Metabolism, Gene Expression, Solid Tumours, biology research, pre-clinical development of innovative Stem Cells. therapeutic strategies and translational research, with a Target Students: PhD/Postgraduate, Honours. focus on upper gastrointestinal cancers. Our research integrates novel in vitro and in vivo models to functionally characterise drivers of tumour development Metabolic rewiring in liver cancer: Role of oxidative and progression, and identify and test new therapeutic stress and the Nrf2 pathway approaches for these cancers. Supervisor: Dr. Andrew Cox Current research topics we are focusing on include: Many of the major risks factors for developing liver cancer • Developing therapeutic strategies for targeting mutant such as alcohol, obesity, smoking and toxin exposure p53 cancers including understanding the effect of share in common a role for oxidative stress. Nrf2 is a mutant p53 on oxidative stress and metabolism transcription factor activated by oxidative stress that orchestrates an adaptive response remodeling metabolism • Understanding mechanisms that regulate a form of cell and promoting cytoprotection. Recent studies have death called “ferropotosis” for exploitation as a process identified that the Nrf2 pathway is frequently mutated to kill cancer cells in liver cancer (~12% tumors), causing activation of the • Performing in vitro and in vivo genome wide CRISPR- pathway in the absence of oxidative stress. We have used Cas9 screens in models of oesophageal cancer to transcriptomic and metabolic profiling in Nrf2-/- zebrafish identify drivers of the disease and novel therapeutic to examine the role Nrf2 plays in remodeling metabolism targets. during liver development and regeneration. For more information about these research directions Building on these preliminary studies, we currently have contact: research projects that aim to 1) Generate a gain of function Nrf2 mutant (Nrf2D29H), frequently recovered in cancer, Dr. Nick Clemons [email protected] and characterize the effect the mutation has on metabolic reprogramming. 2) Examine how deregulation of Nrf2 remodels metabolism to stimulate liver tumorigenesis. COX, ANDREW The students will use a combination of innovative biochemical, genetic and imaging approaches in zebrafish ORGANOGENESIS AND CANCER PROGRAM, & to identify the metabolic dependencies of tissue growth in CANCER METABOLISM PROGRAM liver regeneration and cancer. https://www.petermac.org/research/labs/andrew-cox Key Words: Cancer Cell Biology, Cancer Therapy, Cell Growth, Cell Metabolism, Gene Expression, Solid Tumours, Fishing for metabolic clues: Role of the Hippo/Yap Stem Cells. pathway in reprogramming metabolism in liver cancer Target Students: PhD/Postgraduate, Honours. Supervisor: Dr. Andrew Cox For more information about these projects contact: The Hippo/Yap pathway is an evolutionarily conserved cascade that plays a fundamental role in governing organ Dr. Andrew Cox [email protected] size control, stem cell homeostasis and cancer. The Hippo/ Yap pathway is regulated by a range of environmental cues including nutrient status. Although many of the inputs into the Hippo pathway have been identified, less is known about the Yap target genes responsible for tissue growth. Using a combination of metabolomic and transcriptomic approaches in zebrafish, we have discovered that Yap reprograms glutamine metabolism in vivo to stimulate nucleotide biosynthesis and fuel premalignant liver growth. Building on this initial investigation, we currently have research projects that aim to 1) Examine how Yap coordinates nutrient sensing to metabolic output in the liver. 2) Elucidate the mechanisms by which Yap reprograms metabolism to fuel liver growth in the context

21 AVAILABLE PROJECTS BY RESEARCH GROUP

DARIDO, CHARBEL Cancer, Inflammation, Signalling Pathways, Skin. Target Students: PhD/Postgraduate, Honours/Masters CANCER THERAPEUTICS PROGRAM https://www.petermac.org/research/labs/charbel-darido Identification of biomarkers of response to therapies against head & neck cancer Investigating the requirements of pro-inflammatory signaling in skin and head & neck Squamous Cell Supervisor: Dr. Charbel Darido, Dr. Bryce van Denderen Carcinomas Human head and neck cancer is a devastating disease with Supervisor: Dr. Charbel Darido, Ms Yuchen Bai poor survival rates. Inter-patients, intra-patients as well as intra-tumour heterogeneity limit the response to advanced Squamous cell carcinomas (SCC) are amongst the most therapies resulting in mortality and morbidity. Using a common cancer types afflicting man. SCCs most frequently combined approach of molecular profiling, proteomics, arise from stratified squamous epithelia such as the bioinformatics, drug sensitivity to inhibitors of oncogenic epidermis or the mucosae of the head and neck. We have pathways, and mutational analysis, we identified potential recently identified two novel microRNA-21 (miR-21)- biomarkers of response to treatment. This proejct aims to: dependent proto-oncogenic networks that underpin SCC in skin and head & neck in both mice and humans. - assess potential biomarkers related to resistance or response using in vitro and in vivo laboratory systems and We hypothesize that inflammation in SCC occurs in a tissue- animal models that are designed specifically to investigate specific manner leading to miR-21 induction. The project is heterogeneous head & neck cancer. designed to investigate which upstream pro-inflammatory pathways promote dysregulation of miR-21 in skin versus - understand why some patients respond well to targeted head & neck. Successful completion of this project will therapies and other patients, who clinically appear to have pioneer novel therapeutic approaches and will determine the same type of cancer, respond poorly or not at all. the merit to explore tissue-specific targeted therapies of Successful completion of this project will pioneer novel human SCC to improve clinical outcomes in this disease. therapeutic approaches and will determine the merit to Skills to be taught include molecular biology, biochemistry, explore genomic biomarkers paired with targeted therapies cell culture and knockout mice. to improve clinical outcomes in this disease. Key Words: Cancer, Treatment, Head and Neck Cancer, This research will benefit from collaborative research Inflammation, Signalling Pathways, Skin. across several members of the VCCC alliance including Peter MacCallum Cancer Centre; Royal Melbourne Hospital; Target Students: Honours/Masters University of Melbourne, and the Walter and Eliza Hall Institute, and will contribute to the growing knowledge of response and resistance to targeted therapies. Predicting the development of oral cancer Skills to be taught include drug assays, biochemistry, Supervisor: Dr. Charbel Darido, Dr. Bryce van Denderen molecular biology, cell culture and muse models. Human head and neck cancer is a devastating disease Key Words: Cancer, Treatment, Head and Neck Cancer, with poor survival rates. Oral cancer (OC) is the most Inflammation, Signalling Pathways, Mouse Models. common type of head and neck cancer affecting the oral cavity where it is driven by the continuous exposure to Target Students: Honours. risk factors including tobacco use, alcohol abuse, infection For more information about these projects contact: with high-risk human papilloma viruses (HPV) and genetic pre-disposition. Over the last thirty years, improvements Dr. Charbel Darido [email protected] in survival rates of oral cancer patients have remained modest, hampered by the late diagnosis of the disease. In this project, we will use mouse models of OC that mirror the human malignancy to identify initial molecular changes that predict cancer development. We expect that analysing the tissue integrity in these models of the OC risk factors will provide a window for disease initiation. Discoveries in these models will lead to identification of biomarkers for early diagnosis and disease progression in OC patients. A wide range of skills will be taught including biochemistry, molecular biology, cell culture and knockout mice. This is an ideal project for a student who wishes to pursue higher studies in cancer research. Skills to be taught include biochemistry, molecular biology, cell culture and knockout mice. This is an ideal project for a student who wishes to pursue higher studies in cancer research.Key Words: Cancer, Treatment, Head and Neck

Peter MacCallum Cancer Centre 22 AVAILABLE PROJECTS BY RESEARCH GROUP

DAWSON, MARK investigate how loss of PAR3 and/or SCRIB impact steady-state blood production and leukemia. Cutting edge technologies are employed to determine the intracellular TRANSLATIONAL HAEMATOLOGY PROGRAM signaling pathways that are deregulated upon loss of one https://www.petermac.org/research/labs/mark-dawson or both of these polarity proteins. Depending upon the length of candidature, techniques will include RNAseq, Investigating regulators of anti-tumour immunity quantitative reverse transcription PCR (RT-qPCR), multi- Supervisors: Dr. Brian Liddicoat, Dr. Ewa Michalak, Prof. color flow cytometry, multiplex immunohistochemistry, and Mark Dawson high content western blotting. Interaction between the inhibitory checkpoint molecule Changes in the bone marrow microenvironment during the PD-1 on T cells and its ligand PD-L1 on tumour cells development of leukemia in the presence or absence of inhibits T-cell mediated effector functions and helps cancer SCRIB and/or PAR3 will be examined using state-of-the- cells evade immune destruction. Therapies that block the art intravital microscopy. Importantly, expertise in all these PD1-PDL1 interaction successfully disrupt PD-L1-mediated methodologies exists within the laboratory or within Peter tumour tolerance and are currently being evaluated in Mac’s outstanding core facilities. clinical trials. In an effort to understand the molecular These pre-clinical studies will highlight the role of SCRIB regulation of PD-L1 expression, we and others recently and PAR3 in the onset and progression of leukemia with identified regulators of PD-L1 cell surface expression the ultimate aim of generating novel chemotherapeutic across various cancer types. To understand the roles these targets. regulators, play in immune surveillance, we have generated mouse models that allow us to conditionally delete them in Key Words: Cancer Cell Biology; Cancer Epigenetics; different immune cell subsets. Cancer Signalling; Cancer Therapy; Cell Cycle; Cell Growth, Proliferaiton and Death;. Cellular Immunity; Differentiation; The aims of this project are to examine the immune system Haematology; Haematological Cancers; Innate Immunity; of these mice both during normal development, following Tumour Immunology; Tumour Suppression. immune activation, and in the context of cancer. Students will gain experience in mouse genetics, haematopoiesis, Target Students: PhD/Postgraduate, Honours. FACS analysis, cancer immunology and molecular biology For more information about these projects contact: techniques. A/Prof. Sarah Ellis [email protected] Key Words: Cancer Cell Biology; Immunology; Immune Chekcpoint Inhibitors; Mouse Models. Target Students: Honours. GOEL, SHOM For more information about this project contact: CANCER THERAPEUTICS PROGRAM Dr. Brian Liddicott [email protected] Dr. Ewa Michalek [email protected] https://www.petermac.org/research/labs/shom-goel Prof. Mark Dawson [email protected] Dr Goel has recently been recruited to the Peter Mac from Harvard Medical School, where he developed a number of innovative cell line and transgenic mouse models of breast ELLIS, SARAH cancer. He has already used these models to uncover previously unappreciated mechanisms of CDK4/6 inhibitor CENTRE FOR ADVANCED HISTOLOGY AND activity (Goel, Cancer Cell 2016; Goel, Nature 2017). MICROSCOPY, & CANCER IMMUNOLOGY Discovering better therapies for ER-positive metastatic PROGRAM breast cancer https://www.petermac.org/research/core-facilities/centre- Supervisors: Dr. Shom Goel advanced-histology-microscopy Each year, over 3000 Australians lose their life to Role of the Polarity Proteins, SCRIB and PAR3, in breast cancer. The majority of these women suffer from leukemia metastatic estrogen receptor-positive (ER-positive) Supervisors: A/Prof. Sarah Ellis, A/Prof. Phil Darcy breast cancer, the commonest subtype of the disease. Unfortunately, metastatic ER-positive breast remains According to the Leukaemia Foundation, at least one invariably fatal, largely because cancers develop resistance Australian is diagnosed with leukemia or lymphoma to existing therapies over time. Furthermore, efforts every hour yet the cause of these blood cancers remains to understand why this resistance develops using next relatively unidentified. The evolutionary conserved polarity generation DNA sequencing have been unrewarding, as proteins, Partition Defective 3 (PAR3) and Scribble (SCRIB) the majority of tumours have not acquired new genetic act as tumour suppressors or tumour promoters in a mutations at the time of acquiring resistance. variety of epithelial cancers yet their function in leukemia is largely unknown and is the focus of our laboratory. In the Goel lab, we are focused on identifying the fundamental biological mechanisms that underlie We utilise conditional knockout mouse models to therapeutic resistance in ER-positive breast cancer. 23 AVAILABLE PROJECTS BY RESEARCH GROUP

More specifically, we study why breast cancers develop Key Words: Prostate Cancers; Cancer Genetics; Cancer resistance to a class of cell cycle targeting drugs called Genomics; Bioinformatics; Computational Biology. CDK4/6 inhibitors, which are routinely used in this disease. Target Students: PhD/Postgraduate, In this project, you will have access to these same models and will use them to explore why breast cancers acquire resistance to CDK4/6 inhibition. The project will Finding biomarkers of response to novel therapies for focus on epigenetic and immunologic mechanisms of advanced prostate cancer drug resistance, both novel concepts that have not been explored in breast cancer thus far. Supervisors: Dr. David Goode In the lab, you will have unrestricted access to the Goel This project will tap into unique sets of patient samples lab’s cutting-edge transgenic mouse models of breast collected from ongoing clinical studies at the Peter Mac cancer, and will perform sophisticated molecular biology to develop predictive models of who will respond best to assays including epigenetic profiling of cancer cells and novel treatments for prostate cancer and the reasons why genome editing using CRISPR-Cas9 technology. In addition, these therapies may fail. you will have access to a unique collection of tumour The project will involve devising and applying methods for samples from breast cancer patients, which will allow you integration of longitudinal clinical data with multifaceted to validate your laboratory findings in a clinical context. genomics data sets, including whole-genome and RNA- Key Words: Cancer Cell Biology; Immunology; Immune sequencing, circulating-tumour DNA, microbiome profiling Chekcpoint Inhibitors; Mouse Models. and other technologies. Target Students: PhD/postgraduates. Key Words: Prostate Cancers; Cancer Genetics; Cancer Genomics; Bioinformatics; Computational Biology. For more information about these projects contact: Target Students: PhD/Postgraduate. Dr. Shom Goel [email protected]

Disruption and rewiring of metazoan gene regulatory GOODE, DAVID networks in cancer Supervisors: Dr. David Goode COMPUTATIONAL BIOLOGY PROGRAM , & PROSTATE CANCER PROGRAM The emergence of multicellular life required the evolution of genetic regulatory mechanisms that enforced https://www.petermac.org/research/labs/david-goode communication and cooperation between different cell types. In cancer, many of these of these mechanisms are Transcriptional heterogeneity and resistance to therapy comprised and cooperative growth is diminished in favour in prostate cancer competition between cells. This process is reminiscent of a Supervisors: Dr. David Goode reversion to more ‘unicellular’ state. Androgen deprivation therapy (ADT) is a standard We combine network biology, comparative genomics and treatment for prostate cancer that works well in many large gene expression data sets from various types of cases but rapidly fails in others. Alternate therapies are cancer to assess how genetic regulatory networks set needed for the subset of patients who fail ADT, but it’s up to sustain multicellularity are disrupted and rewired difficult to determine at diagnosis who will respond well to in cancer. This sheds light on the origin of common ADT and other standard therapies and who won’t. This is hallmark features of cancer and helps reveal molecular in part due to massive differences in gene expression both vulnerabilities within tumours that could be targeted within and between tumours of the prostate. potential therapeutic ally. We are using a combination of genomics techniques to Key Words: Cancer Genetics; Cancer Genomics; investigate how genetic and transcriptional heterogeneity Bioinformatics; Computational Biology. relates to drug response in a unique cohort of patient- derived laboratory models that recapitulate the most highly Target Students: PhD/Postgraduate. aggressive forms of the disease. By combining results of drug testing experiments with our genomic analyses, we aim to identify more effective treatments for the most Computational simulation of tumour formation and difficult to cure cases. progression We have begun to apply newly developed single-cell Supervisors: Dr. David Goode RNA sequencing techniques to search for cellular Tumours comprise a complex mix of related but subpopulations within prostate tumours with unique gene distinct cellular subpopulations that both compete and expression signatures that may be driving drug resistance complement one another. These dynamics strongly in our patient-derived models. This approach is opening influence how and when a tumour forms as well as its new frontiers, by revealing previously unappreciated response to therapy, however there are hard to observe prostate tumour cell types that were not apparent in bulk directly. sequencing. Peter MacCallum Cancer Centre 24 AVAILABLE PROJECTS BY RESEARCH GROUP

We are developing sophisticated computational simulations remarkable for such a rare disease, including with clinical, to recreate the growth and spread of cancer cells, and immunohistochemical, gene expression and genomics to model how resistance to cancer drugs may emerge. data (sequencing and copy number). We are also currently By matching our simulated results to data from cancer developing organoid and PDX models from primary patient patients, we aim to understand how early events in tumour material with which to test therapies. formation drive later outcomes and devise improved Further investigations will be undertaken to understand the therapeutic strategies. interaction of our research findings with clinical behaviour Key Words: Cancer Genetics; Cancer Genomics; and response to treatment – this will be tailored to the Bioinformatics; Computational Biology. interest of the student but could include bioinformatics/ data analysis, cell culture and drug screening and genetic Target Students: PhD/Postgraduate,. analysis. Students with an interest in bioinformatics are For more information about these projects contact: especially encouraged to apply. Dr. David Goode [email protected] Key Words: Bioinformatics, Cancer Genetics, Gynaecological Cancers, Solid Tumours, Therapeutics. Target Students: PhD/Postgraduate, Honours. GORRINGE, KYLIE For more information about these projects contact: A/Prof. Kylie Gorringe [email protected] CANCER GENETICS AND GENOMICS PROGRAM https://www.petermac.org/research/labs/kylie-gorringe HARVEY, KIERAN Personalised risk evaluation in DCIS Supervisors: A/Prof. Kylie Gorringe, Prof. Ian Campbell ORGANOGENESIS AND CANCER PROGRAM Breast screening using mammography has seen an https://www.petermac.org/research/labs/kieran-harvey increased detection of not only invasive breast cancer, but also pre-invasive lesions such as ductal carcinoma in situ Watching the Hippo pathway in real time in growing organs (DCIS). The clinical management of DCIS is problematical Supervisor: Prof. Kieran Harvey due to a lack of accurate prognostic and predictive tests. If recurrence risk could be accurately estimated, those A new frontier in biomedical research will involve watching with low risk disease could be offered surgery only, and individual proteins work in real time, in living organs. those with high risk of recurrence have excision plus Traditionally, researchers have drawn conclusions about radiotherapy or a full mastectomy, thus optimising patient gene function using indirect techniques that only allow us to outcomes while minimising treatment toxicity. Thus, infer what a gene normally does, without actually watching our principal research question is: are there molecular it work. For example, we create organisms that lack a biomarkers that can predict which DCIS are at higher risk particular gene and determine whether something goes for recurrence? wrong. If the loss of gene X causes organs to overgrow then we assume that gene X normally limits organ size. This has The project will involve molecular analysis of DCIS cases been an extraordinarily powerful approach for interrogating both with and without later recurrence to identify potential gene function but it cannot substitute the ability to watch biomarkers, which may include DNA mutations, copy gene products executing their function in real time, which number changes, and gene expression. Techniques will allows determination of exactly when, where and how they include DNA/RNA extraction from tumour tissue, analysis work. by next-generation sequencing and/or a Nanostring expression assay. Analysis using in situ methods such as This project will investigate the role Hippo tumour immunohistochemistry and FISH may also be undertaken. suppressor pathway in organ growth by watching growing organs, in real time. This will provide novel insights into Key Words: Breast Cancers; Cancer Genetics; Cancer normal organ growth and pathogenic organ growth in Genomics; Molecular Biomarkers; Pathology; Precision diseases such as cancer. Medicine; Mammography; CLinical Management. The project will investgate Hippo pathway activity in real Target Students: PhD/Postgraduate, Honours. time in the following situations: a) When organs are actively growing b) When organs stop growing Understanding mucinous ovarian cancer c) In regions of organs that are subject to mechanical Supervisors: A/Prof. Kylie Gorringe compression The Gorringe lab has an ongoing project investigating d) Throughout the cell cycle a rare ovarian cancer subtype, mucinous ovarian The student will be taught an array of techniques including carcinoma. This disease has no effective chemotherapies ex vivo organ culture, live multi-photon microscopy, image and women with advanced disease have dire clinical analysis and Drosophila genetics. outcomes. We have a cohort of ~200 mucinous tumours,

25 AVAILABLE PROJECTS BY RESEARCH GROUP

Key Words: Cancer Cell Biology; Cell Signalling; Cell The candidate will use a variety of computational Development, Proliferation and Death; Skin Cancers, Solid approaches, programming languages, and be exposed Tumours; Developmental Biology. to statistical analysis tools. Advance knowledge of stats and ability to interrogate large amounts of data will be Target Students: PhD/postgraduate. advantageous but is not a prerequisite. For more information about this project contact: Information derived from this project will be initially inform Prof. Kieran Harvey [email protected] on the sex disparity in lung cancers, but ultimately will form the basis for the understanding of the disparity in other cancer types. HAUPT, YGAL Key Words: Computational Biology; Cancer Genomics; Bioinformatics; Solid Tumours. PROSTATE CANCER PROGRAM, & ONCOGENIC Target Students: PhD/postgraduate SIGNALLING AND GROWTH CONTROL PROGRAM https://www.petermac.org/research/labs/ygal-haupt Defining the role of p53 in cancer immunotherapy Exploration of novel approaches to anti-cancer Supervisor: Prof. Ygal Haupt, Dr. Sue Haupt treatment: manipulation of mutant p53 Despite clear evidence of an association between Supervisors: Prof. Ygal Haupt , Dr. Sue Haupt the tumour suppressor p53 and immunity, a gap in P53 is the most mutated gene in human cancer, affecting knowledge exists regarding its role in modulating immune about half the cases of cancer, and involved in every cancer responses, or its value in predicting patient responses to type. We have recently identified novel regulators of mutant immunotherapy. Given the unprecedented frequency of p53 p53 using sophisticated loss of function whole genome mutation in cancers and the heterogeneous responses to high content screen. immunotherapy, this question deserves rigorous exploration. In this project the candidate will study a key novel regulator P53 activity has been associated with tumour-infiltration and derived from this screen to explore the interplay with immune activation. Despite the prevalence of p53 mutations mutant p53, and to define novel target for anti-cancer in human cancers (>50%) and its link to immune regulation, drugs. The student will explore the efficacy of manipulating the impact of p53 status on the immune response, and on these regulators as a novel approach to treating cancer the response to immune checkpoint inhibitors has not been cells bearing mutant p53 (majority of human cancers). explored. These fundamental questions, which potentially affect many cancer types and a large proportion of cancer The project will involve work with cancer cell lines, patients, form the basis of this study. transgenic mouse models, and human samples. In addition the project will expose students to a variety of molecular, The project will involve work with cancer cell lines, cellular biochemical techniques, as well as to genomic and transgenic mouse models, and human samples, and bioinformatics analyses. will expose students to a variety of molecular, cellular biochemical techniques, immune profiling, and to genomic Key Words: Breast Cancers; Cancer Cell Biology, Cancer and bioinformatics analyses. Therapy, Therapeutics;,Tumour Suppression. Key Words: Cancer Cell Biology; Cancer Therapy; Target Students: PhD/postgraduate, Honours Immunotherapy; Radiation Therapy; Solid Tumours; Therapeutics; Tumour Immunology. Computational analysis of cancer sex-disparity Target Students: PhD/postgraduate, Honours Supervisors: Prof. Ygal Haupt , Dr. Sue Haupt For more information about these projects contact: For the vast majority of non-reproductive cancers, there is Prof. Ygal Haupt [email protected] a higher rate of cancer morbidity in males than females. Dr. Sue Haupt [email protected] The molecular basis for this disparity is yet to be properly understood. We have recently made a breakthrough in this field by identifying sex-specific genomic molecular signatures, through our computational interrogation of The Cancer Genome Atlas (TCGA). In this project the candidate postgraduate student will pursue this topic. Specifically, the student will use unique data sets that have been generated in the Peter MacCallum Cancer Centre using information derived from the clinics including clinical trials. This information will be tested against publically available databases to validate and test the findings.

Peter MacCallum Cancer Centre 26 AVAILABLE PROJECTS BY RESEARCH GROUP

HICKS, RODNEY of therapeutics to the brain. We have recently developed zebrafish mutants that fail to CANCER THERAPEUTICS PROGRAM maintain pericytes and other mural cell types at the BBB, we have generated single cell sequence-based transcriptomes https://www.petermac.org/research/labs/rodney-hicks of developing pericytes, mural cells and the BBB. We have a series of transgenic lines that label the cells of the https://www.petermac.org/research/labs/carleen-cullinane perivascular niche and BBB, allowing us to investigate its Understanding the mechanisms of neuroendocrine tumour development with unprecedented resolution. response to radionuclide therapy This project will investigate the development, composition Supervisors: A/Prof. Carleen Cullinane, Prof. Rod Hicks and key cellular interactions of the perivascular niche Neuroendocrine tumours (NET) represent a heterogeneous in the zebrafish brain. The PhD candidate will use group of tumours that arise in specialized cells found genetics, genome editing, transgenesis, transcriptomics, throughout the body. Peptide receptor radionuclide bioinformatics and high-resolution imaging of cell behaviour therapy (PRRT) is an effective treatment modality for NET and function in vivo. that involves the use of radiolabelled peptides to target Key Words: Development, Cell biology, Vascular, Blood brain the somatostatin receptor which is widely expressed on barrier, Zebrafish. neuroendocrine cells. Despite its encouraging clinical activity, significant variability in tumour response to PRRT Target Students: PhD/Postgraduate. has been observed. These findings highlight the need to understand the mechanisms underlying tumour response to PRRT in order to identify better methods to select patients Zebrafish models of vascular disease: lymphatic for treatment and to develop novel combination therapies to malformation overcome resistance. Supervisors: Prof Ben Hogan, Dr Kazuhide Okuda This project aims to investigate the determinants of Lymphatic malformation (also known as lymphangioma) is a response to PRRT and develop novel combination regimens rare childhood disease caused by uncontrolled proliferation of PRRT and drugs to further enhance tumour response. of the lymphatic endothelium. These malformations are The project will employ a wide range of in vitro and in typically present at birth, or soon after, and are largely vivo techniques including cell culture, organoid culture, treated with surgery when possible. The genetic causes of molecular biology, preclinical models of cancer and imaging. lymphangioma remain to be fully understood but somatic Key Words: Cancer Cell Biology; Molecular Imaging; mutations in PIK3CA, impacting the AKT-mTOR pathway, Molecular Targets; Radiation Therapy. have emerged as causative in many cases. Several potential molecular therapies have been proposed but their relative Target Students: Honours/Masters, PhD/postgraduate. utilities remain to be fully assessed. For more information about this project contact: The project will generate genetic, inducible, models of A/Prof. Carleen Cullinane lymphangioma in zebrafish and attempt to generate CRISPR- induced models. These will drive vascular malformation by [email protected] expression of mutant PIK3CA expression. Phenotype will be assessed with molecular markers and confocal imaging. The models generated will ultimately be used to assess the efficacy of a series of candidate therapeutic molecules. HOGAN, BEN The project will employ transgenesis, pharmacology, live- imaging of development (confocal) and molecular biology ORGANOGENESIS & CANCER PROGRAM approaches. https://www.petermac.org/research/labs/ben-hogan Key Words: Development, Cell biology, Disease, Zebrafish, Cellular cross-talk at the perivascular niche and the blood Genetics. brain barrier Target Students: Honours. Supervisor: Prof Ben Hogan Much research on vasculature has focussed on the The Hippo pathway and Yap1 in vascular growth control in endothelial cells that line functional vessels, however the development and disease milieu of cells that surround vessels (mural cells) play important and under-appreciated roles in homeostasis Supervisors: Prof Ben Hogan, Dr Andrew Cox and disease. These cells make up the perivascular niche Lymphatic vessels play roles in the drainage of tissue fluid, and play roles in controlling vascular integrity, function, trafficking of immune cells and the metastatic spread of regeneration and permeability. They can also serve as a cancer. Inhibiting or enhancing the development of new niche for maintenance of stem cells and cancer cells. The lymphatic vessels has therapeutic potential in a host of mural cells and endothelium in the brain make up the blood diseases including cancer, ocular disease, cardiovascular brain barrier (BBB), which serves as both a key regulatory disease and rare inherited disorders. The Hogan lab barrier in metastasis and a significant challenge in delivery uses genetic approaches in zebrafish and mice to

27 AVAILABLE PROJECTS BY RESEARCH GROUP discover and characterise new molecular regulators of JOHNSTONE, RICKY lymphangiogenesis (the formation of new lymphatics). We recently described a role for Yap1 in lymphangiogenesis in the zebrafish embryo, in response to Vegfc/Vegfr3 TRANSLATIONAL HAEMATOLOGY PROGRAM signalling. This work, and work from others, has CANCER IMMUNOLOGY PROGRAM confirmed that the Hippo pathway and Yap are central in https://www.petermac.org/research/labs/ricky-johnstone vascular growth during development, yet how they control angiogenesis, lymphangiogenesis, vessel proliferation and Investigating the role of CDK11 in haematological vascular network patterning remains far from understood. malignancies This PhD candidate will use molecular genetics, Supervisor: Dr. Jennifer Devlin, Prof. Ricky Johnstone biochemical approaches and live imaging of cellular Coordinated gene expression requires exquisite behaviours in zebrafish, mice and cultured human cell regulation of transcriptional initiation, pausing, lines to understand the mechanistic control of vascular elongation and termination, as well as co-transcriptional development by the Hippo pathway and Yap. The project mRNA processing, controlled by a class of cyclin- will generate novel CRISPR mutants, new transgenic dependent kinases including CDKs 7, 8, 9, 10, 11, 12 lines and utilise single cell sequencing of developing and 13. Subversion of these fundamental molecular vasculature. We will also investigate metabolic control by processes disrupts gene expression programs and drives the pathway in vascular growth and development. Finally, tumorigenesis, Our lab has demonstrated that small the project will have the opportunity to assess tumour molecule inhibitors of transcriptional CDKs including CDK7 vasculature and pathological settings to understand the (initiation), CDK9 (pausing) and CDK12/13 (elongation) role of this pathway in vascular disease scenarios. induce anti-tumour responses in haematological Key Words: Development, Cell biology, Angiogenesis, malignancies and we have subsequently utilized these Lymphangiogenesis, Zebrafish. inhibitors to investigate the molecular processes that control cellular transcription. Target Students: PhD/Postgraduate Our lab has shown using short-hairpin RNA (shRNA) screens and CRISPR-Cas9 knockout experiments that Cell fates and cell states: analysis of enhancer dynamics CDK11 is essential for the survival of acute myeloid during angiogenesis and lymphangiogenesis leukaemia and multiple myeloma cells. Biochemical studies have demonstrated a role for CDK11 for the control Supervisors: Prof Ben Hogan, Dr Lizzie Mason of gene expression at the level of transcription regulation Cellular fates are regulated by key transcription factors and pre-mRNA processing (e.g. splicing; polyadenylation; during vascular development, angiogenesis and export). However, the exact mechanisms through which lymphangiogenesis. In recent decades, analysis of vascular CDK11 functions are as yet unknown, as no small molecule cell fates, such as artery, vein and lymphatic fates, has inhibitor of CDK11 has yet to be developed. Therefore, our uncovered key transcription factors and target enhancer lab has been developing chemical genetic models in order elements that regulate tissue identity. Nevertheless, to acutely study the activity of CDK11, including i) an auxin- how transcription factors drive dynamic changes in inducible-degron CDK11 mutant system to rapidly deplete vessel growth, dynamic enhancer activities, dynamic cell CDK11 protein and; ii) an analogue-sensitive CDK11 mutant behaviours and cellular heterogeneity in the growing which can be inhibited by a ATP-competitive inhibitory vasculature, remains to be determined. Live imaging analogue. reporters of enhancer activity during zebrafish vascular This project aims to use novel chemical genetic systems development offers a unique opportunity to approach these to study the functions of CDK11, in order to evaluate its fundamental questions. potential as a therapeutic target in haematological cancers, This project will take advantage of a large-scale dataset as well as to investigate its role in the regulation of gene recently generated in the Hogan lab using single cell expression. ATAC-seq data to assess the developing vasculature Key Words: Haematological Cancers; Cancer Cell Biology; of the zebrafish embryo. The project will clone and Gene Expression; Gene Regulation. assess functional enhancers that are lineage specific, evolutionarily conserved and candidate elements that Target Students: PhD/Postgraduate, Honours. may control dynamic cell behaviours during new vessel For more information about this project contact: formation. Transgenesis, molecular genetics and cellular resolution confocal imaging of zebrafish vasculature Dr. Jennifer Devlin [email protected] will be coupled with bioinformatics studies of enhancer Prof. Ricky Johnstone [email protected] conservation and prediction of key functional regulators. Key Words: Development, Cell biology, Angiogenesis, Genomics, Bioinformatics. Target Students: Honours. For more information about these projects contact: Prof. Ben Hogan [email protected] Peter MacCallum Cancer Centre 28 AVAILABLE PROJECTS BY RESEARCH GROUP

KATS, LEV LOI, SHERENE CANCER THERAPEUTICS PROGRAM. TRANSLATIONAL HAEMATOLOGY PROGRAM https://www.petermac.org/research/labs/sherene-loi https://www.petermac.org/research/labs/lev-kats Understanding the interface between genomics and anti- RNA Methylation in normal and malignant blood tumour immunity in breast cancer development Supervisors: Prof. Sherene Loi Supervisor: Dr. Lev Kats, Dr. Joan Jo Our lab is studying the breast cancer immune As is the case with DNA and histones, RNA can also be microenvironment and how we can modulate this with modified and indeed more than 100 chemical groups that therapeutics in order to improve survival from breast decorate all four canonical RNA nucleotides have been cancer. We use in vitro and in vivo models, as well as described. While these modifications undoubtedly carry human tissue and blood samples. We use genomic genetic information, their study has lagged far behind interrogation to understand mechanisms of drug resistance that of DNA and histone modifications and their functional as well as mechanisms of immune responses. We use a relevance remains largely unknown. Methylation of the N6 wide variety of cutting edge techniques including single cell position of adenosine (m6A) is the most common alteration sequencing technologies, CyTOF, flow cytometry and next on eukaryotic messenger RNA (mRNA). generation sequencing. Validation of results may also occur, Recent studies have begun to identify writers, readers and in vivo or in vitro as well as examining and developing novel erasers of this epigenetic mark and have demonstrated therapeutics (such as immunotherapies). that it has broad physiological roles in splicing, RNA Students will learn about breast cancer biology, cell stability and microRNA processing. As m6A does not signaling, immunology, cell culture, mouse handling, affect Watson-Crick base pairing, specialised sequencing therapeutics, flow cytometry, western botting, RT-PCR and methods are required to determine its precise localisation genomic techniques, biostatistics, bioinformatics . in the genome. Particularly suited for students interested in translational We are investigating how regulators of the m6A pathway research, novel therapeutics and clinical applications. control RNA methylation, gene expression and cellular behaviour in normal and malignant blood cells. We are looking for highly motivated students interested in cancer research: these projects may be focused on specific Key Methodologies: CRISPR gene editing, RNAseq, m6Aseq. areas such as bioinformatics, immunologyor cancer Key Words: Haematological Cancers; Cancer Cell Biology; therapeutics or broadly encompass all areas. Gene Expression; Gene Regulation; Animal Models. Key Words: Breast Cancer; Cancer Genetics; Cell Biology; Target Students: PhD/postgraduate, Honours Tumour Immunology; Bioinformatics; Genomics; Personalised Medicine. Target Students: PhD/postgraduate, Honours. Targeting IDH mutations in acute myeloid leukaemia For more information about this project contact: Supervisor: Dr. Lev Kats, Dr. Joan Jo Prof. Sherene Loi [email protected] Acute Myeloid Leukaemia (AML) is an aggressive disease with poor prognosis and development of novel treatment options is urgently needed. Approximately 20% of AML patients carry mutations in genes that encode the McARTHUR, GRANT metabolic enzymes IDH1 and -2. Mutant IDH proteins possess a neomorphic enzymatic activity and produce ONCOGENIC SIGNALLING AND GROWTH the onco-metabolite D-2-hydroxyglutarate (2-HG) that CONTROL PROGRAM, & CANCER THERAPEUTICS modulates numerous pathways implicated in cell fate PROGRAM decisions and cancer. https://www.petermac.org/research/labs/grant-mcarthur Using advanced mouse models we are investigating the molecular mechanisms of response and resistance to IDH A/Prof. Karen Sheppard: Senior Research Fellow inhibitors. Key Methodologies to be used: CRISPR gene editing, RNAseq, m6Aseq. Inhibition of PRMT5 as a cancer therapy Key Words: Haematological Cancers; Cancer Cell Biology; Supervisors: A/Prof. Karen Sheppard, Prof. Grant McArthur Gene Expression; Gene Regulation; Animal Models. Targeted therapy has had profound impact on outcomes for Target Students: PhD/Postgraduate, Honours. cancer patients. Nonetheless significant challenges remain to maximize the clinical benefit of targeted therapies For more information about theseprojects contact: including the discovery of targets beyond driver oncogenes, Dr. Lev Kats [email protected] overcoming or preventing resistance, the combination with immunotherapies, and extending their benefit to cancers with poor outcomes.

29 AVAILABLE PROJECTS BY RESEARCH GROUP

We have been at the forefront of development of targeted effect of these targeted therapies on immune cell function therapies for melanoma through targeting of BRAF, MEK and how these targeted therapies impact on current and more recently CDK4. This work has led to a global immunotherapies. standard of care for BRAF-mutant melanoma of BRAF This Honours/PhD project will initially assess the impact + MEK inhibitors and the progress of the combination of several targeted therapies as single agents or in of BRAF, MEK and CDK4 inhibition into clinical trials. combination on tumour immunogenicity and on immune Our recent preliminary studies have identified Protein cell proliferation and function Arginine Methyltransferase 5 (PRMT5) as a new target for melanoma and potentially oesphageal and pancreatic Key Words: Melanoma, Targeted Therapies, Acquired cancer. In preclinical studies using melanoma cell Resistance, Metabolism, Molecular Oncology. lines and mouse models we have demonstrated that Target Students: Honours. PRMT5 inhibition synergises with CDK4 and BRAF/MEK inhibitors leading to sustained inhibition of melanoma cell For more information about this project contact: proliferation. A/Prof. Karen Sheppard karen.sheppard@petermac. This project will assess the ability of PRMT5 inhibition to org be combined with RAF/MEK/CDK4 pathway inhibitors in several cancers and investigate the mechanisms leading to the robust response. In summary this proposal is Overcoming therapy induced reprogramming of aimed at improving the clinical benefit of BRAF/MEK metabolism in melanoma and CDK4 inhibitors by combining with PRMT5 inhibition Supervisors: Dr. Lorey Smith, Prof. Grant McArthur and extending these combination therapies into cancers with poor outcomes (pancreatic and oesophageal). These Therapies that target oncogenes in cancer have studies will provide mechanistic insight into the action of revolutionised cancer care. The major benefits of targeted PRMT5 inhibitors in RAS/RAF/CDK4 driven tumours and therapies are high response rates and manageable identify patients that will likely benefit from PRMT5 therapy toxicities, however they do not result in cures in the vast including combination therapy. majority of patients. Clinical outcomes of these therapies are limited by cellular adaptation and drug tolerance that Key Words: Melanoma, Targeted Therapies, Acquired allows persistence of residual disease that ultimately Resistance, Metabolism, Molecular Oncology. results in relapse. This project will take a new approach to Target Students: PhD/postgraduate, Honours. address this problem by understanding how cancer cells adapt to targeted therapy, prior to development of overt For more information about this project contact: drug resistance. A/Prof. Karen Sheppard [email protected] Cellular adaptation induced by targeted therapy is characterised by oncogenic network rewiring following initial pathway inhibition. In both preclinical and clinical Impact of targeted therapy on the melanoma immune studies of melanoma, drug induced adaptation reprograms microenvironment metabolism however whether this creates unique Supervisors: A/Prof. Karen Sheppard, Prof. Grant McArthur metabolic liabilities that can be targeted to prevent resistance, and the underlying mechanisms that control The treatment of melanoma is undergoing a fundamental it, are unknown. We hypothesise that targeting metabolic change due to the success of both targeted therapies alterations underlying cancer cell plasticity in response directed at the MAPK/ERK pathway and immunotherapies. to targeted therapy will offer new opportunities to treat Targeted therapies block essential cell signalling pathways minimal residual disease to improve response and that are required for tumour cell proliferation and survival, delay or prevent resistance. This project will investigate while immunotherapies promote the patient’s own immune mechanisms underlying drug-induced cellular adaptation system to eliminate the cancer cells. Both approaches have with a focus on metabolism, using MAPK targeted therapy their limitations. Targeted therapies initially elicit excellent in melanoma as a paradigm. tumour regression, but this response is generally short- lived due to the development of resistance. In contrast, Key Words: Melanoma, Metabolism, Targeted Therapies immunotherapies lead to sustained tumour regression but Target Students: Honours, Masters, PhD/Postgraduate. are only effective in a small number of patients. For more information about this project contact: The difference in patient responses to these therapies suggests that the two approaches might have Dr. Lorey Smith [email protected] complementary roles in cancer treatment, and there are currently several clinical trials combining targeted and immune therapies. Targeted therapies can also enhance or diminish immune responses, thus understanding the effect of targeted therapies on immune cells is essential in advancing the combination of these agents into the clinic. Using melanoma cell lines, mouse models and patient samples, we are currently investigating the direct

Peter MacCallum Cancer Centre 30 AVAILABLE PROJECTS BY RESEARCH GROUP

NEESON, PAUL the use of short and long read sequencing, other omics, chromosomal imaging and bioinformatics approaches to develop better understanding of the molecular events that CANCER IMMUNOLOGY PROGRAM allow and direct neochromosome evolution. https://www.petermac.org/research/labs/paul-neeson Key Words: Bioinformatics, Computational Biology. Supervisor: A/Prof. Paul Neeson Target Students: PhD/postgraduate. The Neeson Laboratory explores the human immune system responses to tumour development and to immunotherapy. We do this using patient samples from Clinical cancer bioinformatics cohort studies or clinical trials. Having made observations Supervisor: Prof. Tony Papenfuss, Prof. Stephen Fox in these samples, we then explore immunotherapy drug combination mechanism of action in model systems to This project will involve developing new bioinformatics provide new information for rational use of these drugs in methods for improved analysis of cancer gene the clinic. hybridisation capture panels, particularly in the area of improved copy number analysis, and analysing the Current research topics we are focusing on include: thousands of samples that have already been sequenced at • Chimeric antigen receptor T cells Peter Mac. • Immuno-Oncology: exploring the immune context of Key Words: Bioinformatics, Computational biology; tumours and immune exhaustion Genomics. • Myeloma Immunology. Target Students: PhD/postgraduate. For more information about these research directions For more information about these projects contact: contact: Prof. Tony Papenfuss [email protected] A/Prof. Paul Neeson [email protected]

Immunostaging for melanoma to accurately predict the PAPENFUSS, TONY risk of relapse after surgery Supervisor: Prof. Tony Papenfuss, Dr. David Gyorki COMPUTATIONAL BIOLOGY PROGRAM This project will utilise a large biobank of clinically https://www.petermac.org/research/labs/anthony-papenfuss annotated samples from patients with melanoma at high risk of relapse after surgery to develop a signature Analytic methods for detecting and making sense of that predicts risk of relapse. By combining readouts somatic genomic rearrangements from various platforms that measure immune-tumour Supervisor: Prof. Tony Papenfuss, Dr. Daniel Cameron engagement as well as known clinicopathological staging information, the project seeks to develop an Building on state-of-the-art methods that the lab has accurate immune-staging algorithm. The project will previously created, this project involves the development build on prospective data collected through Melanoma of a variety of new bioinformatics methods to cancer Research Victoria and biomarker analysis using a number genome sequencing data, including copy number analysis of platforms including circulating tumour DNA, other techniques and methods for the refinement, visualisation circulating biomarkers (microRNA, autoantibodies) as well and classification of genomic rearrangements, and their as genomics analysis. New bioinformatics methods will application to clinical cancer samples. be used to develop a clinically meaningful risk prediction Key Words: Bioinformatics, Computational biology; signature. Genomics. Key Words: Bioinformatics, Melanoma, Translational Target Students: PhD/postgraduate. Immunology. Target Students: PhD/postgraduate. For more information about this project contact: Formation and Evolution of Neochromosomes Supervisor: Prof. Tony Papenfuss, Dr. Alan Rubin Prof. Tony Papenfuss [email protected] Dr. David Gyorki [email protected] Neochromosomes are giant super-numerary chromosomes that drive a variety of forms of rare cancer. We have previously shown that in liposarcomas neochromosomes form by a catastrophic process involving chromothripsis and hundreds of breakage-fusion-bridge cycles. Neochromosomes are a fascinating form of mutation and also represent a powerful model to student complex genomic rearrangements. This project will involve

31 AVAILABLE PROJECTS BY RESEARCH GROUP

PARKER, BELINDA that loss of IFN production is closely linked to an increased risk of rapid metastasis in breast cancer. A new type I IFN has now been identified by Paul Hertzog’s group (IFN CANCER IMMUNOLOGY PROGRAM, & CANCER epsilon) that is expressed in the reproductive tract and is THERAPEUTICS PROGRAM regulated by estrogen. We now want to determine is this https://www.petermac.org/research/labs/belinda-parker IFN could actually promote an anti-cancer response in aggressive breast cancer models, as a less toxic alternative Testing the function of immune suppressive cytokines to use of other classical type I IFNs that have been trialled and cells in bone metastasis in the clinic. Supervisors: A/Prof. Belinda Parker, Dr. Damien Zanker, Dr This project will utilise mouse models of triple negative Katie Owen breast cancer and cell lines derived from patients to test Bone metastasis is a common occurrence in breast the expression and therapeutic implications of IFN epsilon, and prostate cancer that leads to patient morbidity including whether this cytokine can promote anti-tumour and, in many cases, mortality. Treatments that target immunity, enhance response to other therapeutics and bone metastases long-term are lacking and, to date, suppress metastasis. Techniques for this project include immunotherapeutics including checkpoint inhibitors have cell culture, RNA extraction and analysis (using quantitative met with underwhelming responses. In fact, our laboratory reverse transcription PCR (RT-qPCR)), ELISA, western has discovered that immune control of tumour growth blotting, multiplex flow cytometry, immunohistochemistry, in bone is unique and this has highlighted the need for induction and monitoring of tumorigenesis and metastasis bone-specific studies that dissect the tumour cytokines in vivo, immune activation and cytotoxicity assays, and in that lead to immune suppression by altering the balance vitro cell proliferation and apoptosis assays. of immune suppressor and effector cells that promote Key Words: Breast Cancer, Interferons, Immunotherapy, cancer outgrowth. This is an extremely understudied area Metastasis, Innate Immunity, Memory T Cells, Checkpoint of research. Proteins, Anti-Tumour Immunity. This project will measure and manipulate immune Target Students: Honours/Masters. suppressive cytokines (including IL-10), checkpoint proteins (such as PD-1/L1) and immune suppressor cells (such as regulatory T cells) in syngeneic mouse models of breast and prostate cancer to identify prognostic and The role of the breast microenvironment in suppressing therapeutic opportunities to predict, prevent or target bone early cancer invasion metastasis. This will be linked to analysis of primary and Supervisors: A/Prof. Belinda Parker, Prof. Bruce Mann metastatic patient tissues to validate findings in mouse (RMH), Dr. Natasha Brockwell models. Techniques for this project include cell culture, Ductal carcinoma in situ (DCIS) is a pre-invasive stage of CRISPR-cas9 gene editing, RNA extraction and analysis breast cancer, whereby the tumour cells remain restrained (using quantitative reverse transcription PCR (RT-qPCR)), by myoepithelial cells that surround breast ducts. western blotting, flow cytometry, multiplex cytokine Predicting which cases of DCIS will later develop invasive analysis, multiplex immunohistochemistry, induction cancer is difficult, meaning that the majority of patients and monitoring of tumorigenesis and metastasis in vivo, have treatment that may not benefit them. The aim of this immune activation and cytotoxicity assays. project is to assess changes to the myoepithelial cells Key Words: Bone Metastasis, Breast Cancer, Prostate and the surrounding immune cells that are associated Cancer, Cytokines, Immune Suppression, Biomarkers, with disease recurrence, with the ultimate objective Precision Medicine, Immune Suppressor cells, Metastasis- of identifying prognostic biomarkers that will enable Targeted Therapeutics, Innate Immunity, Adaptive individualised treatment options for patients diagnosed Immunity, Checkpoint Proteins, Immunotherapy with early stage breast cancer. Target Students: PhD/postgraduate. Our laboratory has developed a 3D model that mimics the earliest stages of tumour cell invasion beyond the myoepithelial layer. Using this model and high Investigating the function of a novel cytokine in immune throughput screening, we have identified candidate regulation of breast cancer tumour suppressors in myoepithelial cells and now want to confirm their functional role. This project will combine Supervisors: A/Prof. Belinda Parker, Prof. Paul Hertzog use of this model with a large cohort of patient DCIS (Hudson Institute) tissues to identify myoepithelial and immune markers/ Immune therapy is currently being trialled for aggressive cells that have important roles early invasion and could types of breast cancers that fail on conventional therapies, serve as candidate biomarkers of risk of invasive relapse such as chemotherapy. To date, response to checkpoint- after DCIS diagnosis. Techniques for this project include based immunotherapies have been underwhelming, 3D cell culture, live cell imaging, confocal microscopy/ despite their success in other malignancies such as immunofluorescence, RNA extraction and analysis, melanoma. Our laboratory has discovered that a class of western blotting, gene editing, multiplex flow cytometry, cytokines called the type I interferons (IFNs) are secreted immunohistochemistry, immune activation assays, and in from tumour cells to promote anti-cancer immunity and vitro cell proliferation and apoptosis assays.

Peter MacCallum Cancer Centre 32 AVAILABLE PROJECTS BY RESEARCH GROUP

Key Words: Breast Cancer, Invasion, Immune activation, Therapy-induced senescence and stemness in ovarian Myoepithelial Cells, INovel Prognostic Markers, Precision cancer Therapy. Supervisors: Dr. Keefe Chan, Prof. Rick Pearson Target Students: PhD/postgraduate. Cellular senescence is a stress response characterized For more information about these projects contact: by a robust cell cycle arrest and is a brake for malignant transformation. Recent evidence also suggests that A/Prof. Belinda Parker [email protected] senescent cells harbour gene signatures similar to stem Dr. Damien Zanker [email protected] cells, which has implications for tumour dormancy and resistance to anti-proliferative cancer therapies. We have identified putative stemness biomarkers by using PEARSON, RICK transcriptome profiling of oncogene-induced senescent cells. We hypothesise that these biomarkers may also be present in therapy-induced senescent cells and enriched ONCOGENIC SIGNALLING AND GROWTH in a therapy-resistant population of cancer cells. 70% CONTROL PROGRAM, & of ovarian cancer patients have disease recurrence and CANCER METABOLISM PROGRAM emerging evidence suggests that ovarian cancer stem cells contribute to drug resistance and relapse. However, https://www.petermac.org/research/labs/rick-pearson whether therapeutic targeting of ovarian cancer induces mRNA translation reprogramming and metabolic re- senescence and stemness is not well understood. wiring in response to ribosome-targeted therapies This project aims to test this hypothesis by utilising Supervisors: Dr. Jian Kang, Prof. Rick Pearson quantitative real-time PCR, immunoblotting, immunofluorescence, and flow cytometry techniques to: Increased synthesis and activity of ribosomes are associated with oncogenesis downstream of the major 1. Characterize the senescence phenotypes of a panel of oncogenes including MYC, RAS and PI3K. We developed human ovarian cancer cell lines in response to therapy. the selective inhibitor of ribosome biogenesis, CX-5461, 2. Identify the presence of stemness biomarkers in which targets RNA Polymerase I transcription, suppressing therapy-induced senescent cells. ribosomal RNA synthesis. We have showed that combining CX-5461 with inhibitors of mRNA translation markedly 3. Determine the impact of targeting stemness biomarkers improved the efficacy of treating MYC-driven lymphoma in therapy-induced senescent cells. and prostate cancer. We further demonstrated that Key Words: Cancer Cell Biology; Cell Signalling; Cancer targeting of ribosome biogenesis and function results Therapy; Cell Cycle; Cell Growth; Cell Metabolism; in rapid and specific inhibition of translation of mRNAs Gynaeolcological Cancers; Molecular Oncology; encoding translation factors and metabolic regulators and Pharmacogenomics; Skin Cancers (incl. Melanoma); Solid that resistance to this therapy is associated with enhanced Tumours; SenescenceN. translation efficiency of these mRNAs. We hypothesize that (i) targeting oncogene-driven translational re-wiring Target Students: PhD/postgraduate, Honours. of key cellular processes will be a common mode of action For more information about this project contact: of ribosome targeted therapies and (ii) definition of the key networks associated with resistance will enable the Dr. Keefe Chan [email protected] rational design of effective combination therapies for oncogene driven cancers. Activation of targeted DNA Damage Response as a novel Our specific aims are to: therapy for Ovarian Cancer 1. Identify and characterise additional drivers of Supervisors: Dr. Elaine Sanij, Prof. Rick Pearson resistance of MYC-driven lymphoma to ribosome- targeting therapies by a comprehensive program of High-grade serous ovarian cancer (HGSOC) is the most polysome profiling, genome sequencing and high- common and aggressive subtype of ovarian cancer and throughput genomic screens. accounts for 70% of all ovarian cancer deaths. HGSOC patients are treated by surgery and/or chemotherapy, yet 2. Investigate the effectiveness of targeting mRNA within 5 years most of these women relapse making new translation or metabolic pathways in multiple mouse treatment options essential. models of MYC-dependent blood cancer. We developed a “first in class” drug, CX-5461 that activates Key Words: mRNA Translation; Cell Metabolism; Cancer DNA damage response, selectively kills cancer cells and Cell Biology; Cell Signalling; Cancer Therapy; Cell Growth; is in clinical trials in haematologic (Peter Mac) and breast Haematological Cancers; Ribosome Biogenesis. cancers (Canada). Importantly, our studies demonstrate Target Students: Honours. substantial efficacy of CX-5461 in HGSOC, which is the basis of a new trial in ovarian cancer we planned in For more information about this project contact: 2018/19. Dr. Jian Kang [email protected] 50% of HGSOC is characterized by defects in the

33 AVAILABLE PROJECTS BY RESEARCH GROUP homologous recombination (HR) DNA repair pathway. PHILLIPS, WAYNE Aberrations in DNA repair provide a weakness that can be exploited therapeutically with genotoxic chemotherapy and inhibitors of DNA repair such as PARP inhibitors (PARPi), GASTROINTESTINAL CANCER PROGRAM now approved in the clinic. Our data demonstarte that CX- https://www.petermac.org/research/labs/wayne-phillips 5461 in combination with PARPi has significant therapeutic benefit against HGSOC patient-derived xenograft models. The role of oesophageal submucosal glands in epithelial homeostasis and the development of Barrett’s This project aims to investigate the efficacy of CX-5461 oesophagus in combination with chemotherapy and inhibitors of DNA repair and DNA damage response in pre-clinical models of Supervisors: Prof. Wayne Phillips, Dr. Nick Clemons HGSOC to facilitate clinical trials of effective combination Barrett’s oesophagus, the premalignant precursor of therapies. oesophageal adenocarcinoma, is a metaplastic condition Key Words: Cancer Cell Biology; Cell Signalling; Cancer where the normal stratified squamous epithelium that Therapy; Cell Cycle; Cell Growth; Cell Metabolism; lines the oesophagus is replaced by an intestinal-like Gynaeoncological Cancers; Molecular Oncology; columnar epithelium. Barrett’s oesophagus arises as Pharmacogenomics; Solid Tumours. a result of chronic reflux but the cellular origin of the intestinal-like metaplastic cells that characterise this Target Students: PhD/postgraduate, Honours. condition is contentious. The current prevailing view, based For more information about this project contact: almost exclusively on rodent models, is that they arise from cells residing at the squamo-columnar junction, Dr. Elaine Sanij [email protected] where the oesophagus joins the stomach. However, using pig oesophagus (which is structurally more similar to human oesophagus than rodents) as a model, we have A multiple modality approach for targeting treatment- shown that specialised glands in the oesophageal sub- resistant ovarian cancer mucosa contain progenitor cells that we believe are Supervisors: Dr. Elaine Sanij, Prof. Rick Pearson responsible for the maintenance of the normal squamous mucosa and may also be the potential cell of origin of High-grade serous ovarian cancer (HGSOC) accounts Barrett’s oesophagus in humans. for 70% of ovarian cancer (OvCa) deaths and its five- year survival rate is 43%. 50% of HGSOC demonstrate This project will define the heterogeneity, hierarchy deficiencies in the homologous recombination (HR) DNA and functional relationships of cell populations in these repair pathway, most commonly mutations in BRCA1/2, glands at the single cell level to identify these progenitor which underpin favourable responses to chemotherapy and cells, and use our novel organoid culture systems to Poly-(ADP-ribose) polymerase (PARP) inhibitors (PARPi). demonstrate their potential to differentiate into either However, most women relapse within three years and normal squamous epithelium and/or Barrett’s-like succumb to chemo- and PARPi-resistant disease. intestinal epithelium. The study will also investigate the ability of acid and bile (components of refluxate) and/or Immunotherapy has emerged as a new promising inflammatory mediators to control the fate of submucosal therapeutic approach in cancer care, however, the gland progenitor cells thus demonstrating an important response to single immunotherapy agents in OvCa is physiological role for the submucosal glands and providing modest (6-30%). OvCa is considered immunologically “cold” important new knowledge about the mechanisms of both and immunosuppressed due to decreased expression of normal oesophageal homeostasis and the development of Type I interferon (IFN) genes, low level of T cell infiltration Barrett’s oesophagus. and poor response to T cell checkpoint inhibitors. This proposal addresses a significant clinical need in developing Key Words: Cancer Cell Biology; Oesophageal Cancer; effective treatments for refractory OvCa and in applying Intestinal Metaplasia; Barrett’s Oesophagus; Epithelial immunotherapy to “cold” OvCa tumours. Homeostasis. This project aims to identify efficacious combination Target Students: PhD/postgraduate. therapy regimens that incorporate the novel RNA For more information about this project contact: polymerase I (Pol I) transcription inhibitor CX-5461 and DNA damage response inhibitors for treatment of relapsed Prof. Wayne Phillips [email protected] OvCa. We aim to identify strategies that enhance anti- tumour immunity, and to design optimal combination therapies with immunotherapies to enhance anti-tumour efficacy and improve survival in ovarian cancer. Key Words: Ovarian Cancer; DNA Repair; Immunology; Novel Combination therapies. Target Students: PhD/postgraduate, Honours. For more information about this project contact: Dr. Elaine Sanij [email protected] Peter MacCallum Cancer Centre 34 AVAILABLE PROJECTS BY RESEARCH GROUP

RISBRIDGER, GAIL to improve outcomes for PC patients, including the use of combination therapies to better target tumour heterogeneity. PROSTATE CANCER PROGRAM This project will characterise the progression of NEPC https://www.petermac.org/research/labs/gail-risbridger using patient-derived models (xenografts and organoids), and test new treatment strategies for this aggressive Pre-clinical testing of novel combination therapies in prostate cancer subtype. mouse models of prostate cancer Supervisor: Dr. Luc Furic Key Words: Cancer Cell Biology; Endocrinology; Pathology; Prostatre Cancer; Solid Tumours; Therapeutics; Urological The prostate requires androgens for normal growth and Cancers. functioning and the vast majority of prostate cancer (PC) are dependent on the androgen receptor (AR) for growth and Target Students: PhD/postgraduate, Honours. proliferation. Androgen-deprivation therapy (ADT) remains For more information about this project contact: the mainstay of therapy for advanced PC, but the disease invariably progress to a stage known as castration-resistant Dr. Roxanne Toivanen [email protected] PC (CRPC). The last decade has seen the development of many new therapeutic agents targeting AR activity directly by inhibiting its transcriptional activity or indirectly by inhibiting New human models for rapid preclinical testing of the enzymes responsible for androgens synthesis. These prostate cancer agents have successfully increased survival in CRPC, but Supervisor: Prof. Gail Risbridger, Dr. Luc Furic resistance emerges in a matter of months. It is therefore urgent to develop and validate new therapeutic targets in PC Prostate cancer is the most commonly diagnosed cancer in which are independent of AR activity. Victoria. Unfortunately, our ability to pre-clinically test new therapies is constrained by the paucity of experimental This project will use genetically modified mouse models human models because prostatic tumours are more (GEMM) of PC to test novel small molecule inhibitors difficult to grow in the laboratory than many other types targeting key vulnerabilities of PC cells. In addition, we are of cancer. However, our laboratory has successfully also developing and testing therapeutic antibodies and a new developed in vivo and in vitro systems to maintain viability vaccine technology. of rare and valuable patient samples as “patient-derived Key Words: Cancer Cell Biology; Cell Signalling; Cancer xenografts and explants/organoids”. These samples Therapy; Cell Growth; Molecular Targets; Solid Tumours; represent an invaluable resource for testing novel Therapeutics; Prostate Cancer. therapeutics for prostate cancer. Target Students: PhD/postgraduate, Honours. The goal of this project is to use patient-derived xenografts as ex vivo explant cultures or organoids to test drugs of For more information about this project contact: interest that are in development and identify the most Dr. Luc Furic [email protected] promising compounds for further in vivo studies. The project will involve a variety of techniques including tissue pathology, tissue culture and handling, Analysing the progression of neuroendocrine prostate immunohistochemistry, automated image analysis and cancer qPCR. Supervisor: Prof. Gail Risbridger, Dr. Roxanne Toivanen Key Words: Cancer Cell Biology; Cell Signalling; Cancer One-in-seven men will be diagnosed with prostate cancer Therapy; Cell Growth; Molecular Targets; Solid Tumours; (PC) in their lifetime. As the majority of prostate tumours are Therapeutics; Prostate Cancer. dependent on androgens for growth, androgen deprivation is Target Students: PhD/postgraduate, Honours. the gold standard treatment for metastatic disease. However all patients inevitably acquire resistance to androgen For more information about this project contact: deprivation, and this most aggressive state is referred to as Dr. Luc Furic [email protected] castration-resistant prostate cancer (CRPC). Prof. Gail Risbridger [email protected] While, new anti-androgen treatment regimens have delayed the onset of metastatic CRPC (mCRPC), it remains a lethal condition with limited treatment options, which at best provide short-term disease control. Furthermore, in an increasing subset of PC patients, androgen-targeted treatment selection pressure leads to the emergence of CRPC with neuroendocrine features. Indeed, the prognosis of patients with neuroendocrine differentiation (NEPC) is extremely poor owing to the resistance to conventional therapies. Consequently, new therapeutic strategies to target CRPC in general and NEPC in particular, are critical

35 AVAILABLE PROJECTS BY RESEARCH GROUP

RUSSELL, SARAH Migration of lymphatic endothelial cells (LECs) – the cells lining lymphatic vessels – is an essential process in lymphangiogenesis. We used a genome-wide siRNA screen CANCER IMMUNOLOGY PROGRAM combined with in vivo-derived datasets to identify dozens of candidate genes involved in LEC migration2. This project https://www.petermac.org/research/labs/sarah-russell will involve characterising one or more of these candidates, How is fate determined during T cell development, which can be selected according to the student’s interests leukemogenesis and responses and skills. Students will use advanced microscopy, multiplex Supervisor: Dr. Sarah Russell immunohistochemistry, analysis of cancer patient samples, functional cell biological assays, molecular biology techniques Understanding how cell fate programming works will and preclinical models to determine the function and lead to improved diagnostic and therapeutic opportunities therapeutic tractability of these genes. for leukemia, and to improved immunotherapies for cancer and infectious disease. We have developed new 1. Stacker SA et al. (2014) Nat Rev Cancer 14(3):159-72; 2Williams SP et al. and methods for imaging single cells and their progeny Stacker SA (2017) Sci Signal 10(499):eaal2987 through many generations of T cell development and Key Words: Metastasis; Solid Tumours; Vascular Biology; activation. These methods mean that we can now Cancer Therapy. assemble pedigrees that describe both the relationships between different differentiation stages, and molecular Target Students: PhD/postgraduate, Honours and behavioral attributes of their ancestors and progeny. The next step is to use these pedigrees and the wealth of information associated with them to determine the Understanding tissue-specific vasculature in cancer relative contributions of genetic, epigenetic, extrinsic and metastasis stochastic influences on fate determination. Supervisors: Prof. Steven Stacker, Dr. Rae Farnsworth This PhD project will involve development of new computational approaches to determine how behaviours in Cancer is a diverse disease, with each tumour differentiated the T cell progeny (differentiation, growth, death, division) by the organ and cell type of origin, the patient’s genetic and are influenced by ancestory, intrinsic and extrinsic cues. clinical background, and the non-mutated cells that comprise the tumour microenvironment. Blood and lymphatic vessels Key Words: Cell Signalling;Cellular Immunology; serve important physiological functions in almost all tissues Differentiation; Haematology; Haematological Cancers; and organs of the body, and can be hijacked by tumours to Immunotherapy; Tumour Immunology. aid in tumour growth, metastasis and regulating immune Target Students: PhD/postgraduate, . responses1,2. The heterogeneity of blood and lymphatic vessels and their component endothelial cells in different organs is For more information about this project contact: only partially characterised, and less still is understood about Dr. Sarah Russell [email protected] how these differences contribute to tumour behaviour and therefore to cancer outcomes in patients. This project will use cutting-edge technologies such as single- STACKER, STEVEN cell RNA-Seq to elucidate the unique molecular profiles of organ-specific lymphatic and blood endothelial cells in mouse TUMOUR ANGIOGENESIS PROGRAM models of cancer. The project will then utilise cell sorting, multiplex immunohistochemistry, organotypic co-culture https://www.petermac.org/research/labs/steven-stacker assays, molecular and cell biological techniques, analysis of Novel regulators of lymphangiogenesis and lymphatic human tumour samples and preclinical models to understand remodelling in tumour metastasis the role of tissue-specific features of the blood and lymphatic vasculature in tumour progression. Supervisors: Prof. Steven Stacker, Dr. Rae Farnsworth 1. Farnsworth RH, Achen MG and Stacker SA (2018) Curr Op Immunol 53:64- The ability of tumour cells to escape the primary tumour site 73; 2. Hendry SA, Farnsworth RH et al. (2016) Front Immunol 7:621 and metastasise to distant organs is the most lethal attribute Key Words: Solid Tumours; Vascular Biology; Transcriptomes; of solid cancers. There is now extensive evidence from clinical Cancer Microenvironment; Metastasis. and experimental studies that the growth and remodelling of tumour-associated lymphatic vessels is linked with increased Target Students: PhD/postgraduate, Honours metastasis to lymph nodes and distant organs, and overall to For more information about these projects contact: poorer prognosis1. Inhibition of key pathways regulating this tumour-associated lymphangiogenesis inhibits metastasis Prof. Steven Stacker [email protected] in experimental models. However, clinical experience with Dr. Rae Farnsworth [email protected] anti-angiogenesis drugs indicates that targeting multiple pathways may be necessary to fully inhibit tumour-associated lymphangiogenesis and thereby lymphogenous metastasis.

Peter MacCallum Cancer Centre 36 AVAILABLE PROJECTS BY RESEARCH GROUP

Understanding how obesity drives the development of TIGANIS, TONY liver cancer CANCER METABOLISM PROGRAM Supervisors: Prof Tony Tiganis, Dr. Florian Weide https://www.petermac.org/research/labs/tony-tiganis Obesity is a leading factor in the development of liver disease, with >85% of overweight individuals developing Metabolic Reprogramming in Liver Cancer non-acloholic fatty liver disease (NAFLD). NAFLD Supervisors: Prof Tony Tiganis, Dr. Florian Weide encompasses a broad spectrum of liver conditions ranging from simple steatosis, to the more severe and progressive Primary liver cancer is one of the world’s deadliest non-alcoholic steatohepatitis (NASH), a condition that cancers. It is the 5th most common cancer worldwide results in fibrosis and if left unresolved, cirrhosis (late- and represents the 3rd most common cause of cancer stage liver disease) and/or liver cancer. death. Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers and is refractory to nearly all Obesity-associated NASH is currently the third leading currently available anti-cancer therapies with a 5 year cause for liver transplantation and is expected to soon survival rate of <9%. In Australia HCC represents the surpass hepatitis C as the principal cause for liver most rapidly rising cause of cancer death. Worryingly transplantation and hepatocellular carcinoma (HCC) in the the incidence of HCC in developed countries has been developed world. increasing driven by the obesity epidemic, the associated Projects are available to determine the mechanisms by development of non-alcoholic fatty liver disease (NAFLD) which obesity drives the development of NASH, fibrosis and its progression to the more aggressive non-alcoholic and HCC. steatohepatitis that results in liver fibrosis/cirrhosis. As the early stages of NAFLD/scarring are asymptomatic, Key Words: Cancer Cell Biology; Cancer metabolism; Cell patients with HCC typically present with advanced disease. Growth; Solid Tumours Standard chemotherapy responses are poor, in most Target Students: PhD/postgraduate. cases having no impact on overall survival rates, whereas the only targeted FDA-approved drug for HCC, Sorafenib For more information about these projects contact: (a multi-targeted oral tyrosine kinase inhibitor) prolongs Prof. Tony Tiganis [email protected] survival by only 2-3 months. Thus there is an urgent need for new therapeutics. Projects are available to delineate the role of reactive TRAPANI, JOSEPH oxygen species (ROS) in tumour development and determine if selectively targeting redox pathways may be effective in suppressing HCC growth and maintenance. In CANCER IMMUNOLOGY PROGRAM particular we will take advantage of exciting new findings https://www.petermac.org/research/labs/joseph-trapani in the cancer field suggesting that the reliance of many tumours on ROS for their growth, may also be their Reengineering of CRISPR–CAS effectors for targeted Achilles’ heel and that exacerbating the toxic effects of ROS cancer therapy may promote cell death and help eradicate tumours Supervisors: Prof. Jospeh Trapani, Dr. Mohamed Fareh Key Words: Cancer Cell Biology; Cancer metabolism; Cell Genetic aberrations drive high-risk pediatric cancers that Growth; Solid Tumours are often correlated with poor prognosis. Recent advances Target Students: PhD/postgraduate, Honours. in genomic technologies revealed the genomic landscape in pediatric neoplasms and highlight an important intra- and inter-tumour genetic heterogeneity. Given the genomic Using T cells to eradicate cancer singularity of individual tumors and/or tumour subclones, it is undeniable that targeted therapies will offer better Supervisors: Prof Tony Tiganis, Dr. Florian Weide survival chances to individual child. The inability of the adaptive immune system to initiate a Recent breakthrough discoveries have identified a new robust anti-tumour response is often linked to the poor subclass of bacterial CRISPR–CAS effectors that target prognosis of patients. Immunotherapy is poised to play a bacteriophages genes with incredibly high fidelity. These central role in the treatment of varied human cancers. The discoveries open the possibility of reprogramming CRISPR– project will take advantage of multidisciplinary techniques CAS effectors to target any disease-related gene in a and utilise both cell-based and animal models to develop sequence-specific manner. A single guide RNA (gRNA) novel approaches for enhancing cytotoxic T cell responses loaded into CRISPR-CAS effectors mediates the sequence in the context of T cell adoptive immunotherapy. specificity through the base-pairing with the target, making Key Words: Cancer Cell Biology; Cancer metabolism; Cell these nucleoprotein complexes promising programmable Growth; Solid Tumours tools to achieve specific-specific and efficient targeting of various tumour drivers. This project will focus on: Target Students: PhD/postgraduate/Honours

37 AVAILABLE PROJECTS BY RESEARCH GROUP

1. Understanding the molecular basis of CRISPR–CAS WICKRAMASINGHE, VIHANDHA target recognition. 2. Reengineering CRISPR-CAS effectors to silence ONCOGENIC SIGNALLING AND GROWTH tumour-associated genes with single-nucleotide CONTROL PROGRAM accuracy. https://www.petermac.org/research/labs/vihandha- In this proof-of-concept project and through our wickramasinghe collaboration with the Zero Childhood Cancer program, we will exploit whole-genome sequencing data and patients’ Mechanisms of regulating gene expression via selective samples (400 paediatric tumors) to reprogram CRISPR– mRNA transport CAS effectors to silence drivers of paediatric tumours such Supervisor: Dr. Vi Wickramasinghe as gene-fusions and single-nucleotide variants. We believe the outcome of this project will help to lay the foundations A critical step in the gene expression pathway that is of a new era of targeted cancer therapies. altered in cancer is nuclear export of mRNA. We have demonstrated that mRNA export is not constitutive, A prospective student will have the opportunity to use but highly selective and can regulate distinct biological cutting-edge interdisciplinary approaches including processes through poorly understood mechanisms. This molecular cloning, CRISPR–CAS genome editing, single- project aims to dissect the molecular mechanisms of molecule super-resolution microscopy, RNA/protein regulating gene expression via selective mRNA transport. purification and labeling, high-throughput cell-based This will establish selective mRNA export as a novel area assays, preparation of DNA libraries, RNA-seq, FACS, RT- of research in cancer biology. PCR, and targeted delivery assays. We offer project(s) in each of these areas, and a specific topic will be selected to Key Words: Cancer Cell Biology; Cell Signalling; Cancer cater for the interests and skills of a candidate. Therapy; Cell Cycle; Cell Growth; Cell Metabolism; Gene Expression; Gene Regulation; microRNA. Key Words: Cancer Immunology, Cancer Immunotherapy, Paediatric tumors, Personalized Immunotherapy, RNA Target Students: PhD/postgraduate, Honours. Therapeutics, Immunoprofiling, Genomics For more information about this project contact: Target Students: Honours. Dr. Vihandha Wickramasinghe For more information about this project contact: [email protected] Dr. Mohamed Fareh [email protected]

Peter MacCallum Cancer Centre 38 AVAILABLE PROJECTS BY RESEARCH GROUP CLINICAL RESEARCH GROUPS AUSTRALIAN CANCER SURVIVORSHIP NATIONAL CENTRE FOR INFECTIONS CENTRE IN CANCER https://www.petermac.org/research/clinical-research-trials/ clinical-research/australian-cancer-survivorship-centre- https://www.petermac.org/research/clinical-research-trials/ research clinical-research/infectious-diseases-infection-prevention The Australian Cancer Survivorship Centre – A Richard The National Centre for Infections in Cancer (NCIC) is an Pratt legacy (ACSC) undertakes survivorship research with integrated health care program for reducing infections in a range of collaborators. cancer. Cancer patients are a unique population with How to we define and measure optimal care for cancer specialised needs. There is compelling evidence that survivors? infection in cancer patients remains a leading cause of death and a significant cost to the healthcare system. Our Supervisors: Dr. Karolina Lisy, Prof. Michael Jefford, Helana research group aims to optimise patient outcomes using a Kelly health services approach to prevent and manage the Over 35,000 Victorians are diagnosed with cancer annually, critical and growing problems of healthcare associated and and most will become long-term survivors. Over 290,000 antibiotic resistant infection, poor sepsis and antimicrobial Victorians have a personal history of cancer. Survivors may management and late recognition of infection in this experience a range of consequences as a result of cancer vulnerable population. and its treatments. Current models of survivorship care are suboptimal, though there are substantial efforts to improve Epidemiology of Staphylococcus aureus bloodstream care delivery. infections in patients with cancer The aims of this project are to define standards of quality Supervisor: A/Prof. Leon Worth survivorship care and develop a set of measurable quality indicators which may be used to benchmark current Bloodstream infections due to Staphylococcus aureus practice and facilitate service improvement across Victoria. (SAB) are a significant cause of morbidity and mortality, To address these aims, the student will undertake: 1) a and are associated with increased healthcare costs. systematic review to identify possible quality domains; 2) Patients with cancer are considered at high risk for a Delphi process with a range of stakeholders (consumer, infection due to a number of factors, including underlying health professional, government and policymaker) to reach malignant disease, the need for invasive procedures, consensus on a final set of quality standards and indicators and presence of indwelling medical devices (e.g. long- for survivorship care in Victoria; 3) a dissemination and term central venous catheters for administration of evaluation plan. chemotherapy). In Australia, the epidemiology of SAB in cancer populations has not been reported, and risks for Project outcomes will have: infection are not well understood. • state-wide implications and national relevance for cancer The objective of this project is to evaluate the risks, survivorship policy and care treatment and outcomes of SAB in cancer patients over • relevance for the next Victorian Cancer Plan: 2020-2024 a 8-year period, using historic surveillance data at Peter MacCallum Cancer Centre (2011-2018). Burden of illness • interest from key stakeholders, including the Victorian will evaluated in terms of length of hospitalisation, ICU Government and Integrated Cancer Services admission, complications and mortality. Community- and The student is anticipated to publish a first-author journal healthcare-associated events will be compared. The article and present results at relevant conferences/ study will be structured as a case-control study, with the meetings. potential for economic analysis to also be performed. Findings will be published in peer-reviewed literature. Key Words: Oncology, Survivorship, Patient Care, Quality Study outcomes will also be used to develop effective of Care, Qualitative Research, Health Services Research, infection prevention strategies and guidelines, and to Health Policy. inform policy regarding use of SAB as a performance Target Students: Honours. indicator. For more information about this project contact: Key Words: Epidemiology; Haematological Cancers; Infectious Disease and Control; Solid Tumours. Dr. Karolina Lisy [email protected] Target Students: PhD/Postgraduate, Honours/Masters Prof. Michael Jefford [email protected] For more information about this project contact: Helana Kelly [email protected] A/Prof. Leon Worth [email protected]

39 AVAILABLE PROJECTS BY RESEARCH GROUP CLINICAL RESEARCH GROUPS Investigation of the incidence and predictive factors of PARKVILLE FAMILIAL CANCER osteoradionecrosis (ORN) of the jaw in the treatment of head and neck cancer CENTRE CENTRE

Supervisors: Dr. Sophie Beaumont, Prof. Krin Thursky, Dr. https://www.petermac.org/research/clinical-research-trials/ Lachlan McDowell clinical-research/familial-cancer-research-centre Osteoradionecrosis (ORN) of the jaw is a serious complication secondary to treatment of head and neck Familial cancer research at Peter Mac combines clinical cancer. ORN can occur spontaneously or in relation and laboratory-based research to: identify new hereditary to oral cavity trauma, including dental procedures or cancer predisposition genes; improve the identification of irritation from an ill-fitting dental prosthesis. Currently, the people with hereditary cancer syndromes; and develop management of patients with ORN is heterogeneous, owing new strategies for cancer risk management and to differing referral patterns and the variable involvement personalising cancer treatments. of multiple clinical teams. The classification and care pathway of ORN is not universally agreed upon. leading to variations in outcomes Understanding Breast and Ovarian Cancer Families: the and management. Typical management strategies Variants in Practice (ViP) study range from simple, local management of oral hygiene, Supervisor: A/Prof. Paul James to debridement, surgical excision, antimicrobial therapy, medical therapy and hyperbaric oxygen treatment. Failure Breast and Ovarian cancer both have a strong hereditary to identify early cases of ORN and suboptimal management basis, the greatest part of which remains unexplained. We may lead to mandibular fracture, necessitating wide field have assembled a unique cohort of hereditary breast and excision of necrotic bone with a large soft tissue and bony ovarian cancer (HBOC) families, known as the ViP study defect requiring reconstruction, heralding a significant to investigate the clinical and genetic features of these decline in survivors’ quality of life. cancers. This established, large cohort includes more than 4500 families with extensive pedigree, pathology, and This project will analyse the population of patients with clinical data along with in-depth sequencing of rare genetic a diagnosis of osteoradionecrosis (ORN) seen at Peter variants and common polymorphisms and prospective MacCallum Cancer Centre to gain an understanding of their follow-up data. cancer treatment history including surgery and radiation therapy, comorbidities and other factors that might In this project, the candidate will be based in the Peter influence the risk of developing ORN. Mac Familial Cancer Centre and will use pedigree-based statistical techniques to mine this enormous data set with This project will be conducted through the Melbourne the aim of identifying novel genomic contributions to HBOC, Dental School. combining complex genomic data into personalised risk Key Words: Head and Neck Cancers; Infectious Disease assessments and creating the detailed information to use genomics in clinical practice. Target Students: Honours/Masters. This project is suitable for a candidate with a strong For more information about this project contact: background in biostatistics or bioinformatics and an Dr. Sophie Beaumont [email protected] interest in clinical genomics. Key Words: Biostatistics; Bioinformatics; Breast Cancer; Cancer Experience; Familial Cancer; Genomics; Health Service Research; Ovarian Cancer. Target Students: Honours. For more information about these projects contact: A/Prof. Paul James [email protected]

Assessing the introduction of a novel personalized genome-based breast cancer risk assessment to women at a familial risk Supervisors: A/Prof. Alison Trainer, A/Prof. Paul James, Health Economist Familial cancer services (FCSs) evolved offering categorical risk assessments (high, moderate, low risk) based on family history or genetic tests for rare high-risk gene mutations such as in BRCA1/2. With the advent of massively parallel sequencing, came the ability to produce

Peter MacCallum Cancer Centre 40 AVAILABLE PROJECTS BY RESEARCH GROUP CLINICAL RESEARCH GROUPS tailored personalized risk assessments by combining Skill set gained: Computer coding and microsimulation results from a spectrum of risk alleles, rare high-risk, modelling; Multicriteria decision analysis; Genomic BC risk and moderate risk as well as multiple low risk alleles modelling; BC health services clinical research. (polygenic risk). This form of continuous risk assessment Key Words: Breast Cancer; Familial Cancer; Genomics. has potential to impact on cancer treatment as well as the cancer risk-specific management of healthy women. Target Students: Honours. The Parkville familial cancer service has well-established For more information about this project contact: clinical and research expertise in this exciting area. A/Prof. Alison Trainer [email protected] This project will assess the impact of offering this form of comprehensive risk assessment to affected and healthy women attending the FCS, including its impact on clinical Psychosocial Onco-Genomic Research Group decision- making by both patient and clinician, as well as on clinical outcome. Familial cancer researchers also investigate the wider psychosocial impact of these syndromes on the well-being Part of the project will be to use these data to further of individuals and their families through the work of the refine an established health economic model to assess Psychosocial Onco-Genomic Research Group. the cost effectiveness of this approach to risk assessment. Experience will be gained in discrete choice experiments Developing a patient reported outcome measure as well as economic assessments. for assessment of family communication of genetic information Key Words: Biostatistics; Bioinformatics; Breast Cancer; Cancer Experience; Familial Cancer; Genomics; Health Supervisor: Laura Forrest Service Research; Ovarian Cancer. The diagnosis of an inherited predisposition to cancer not Target Students: Honours. only has health implications for the diagnosed individual, but also their family members. For this reason, a critical For more information about this project contact: element of the genetic counselling process is identifying A/Prof. Alison Trainer [email protected] which family members are at risk and encouraging the diagnosed individual to communicate the genetic information to these relatives. Concern that communicating Integrating genome-based breast cancer risk prediction genetic information is challenging is evidenced by the models with evidenced-based clinical outcomes and low uptake of clinical genetics services by at-risk family patient values to empower women considering risk- members for predictive genetic testing. There is currently reducing contralateral and bilateral mastectomy no formal assessment encompassing patient reported outcomes specific to family communication for use in Supervisors: A/Prof. Alison Trainer, Lara Petelin, A/Prof. clinical genetics services. Paul James, Prof. Bruce Mann The aim of this project is to develop and refine a list There is increasing demand for contralateral risk-reducing of items that will form the basis of a PROM for family mastectomy(CRRM)in women with breast cancer(BC), communication of genetic information. This project will despite the majority having a low future BC risk, whilst use the Delphi technique to refine the list of items with the many women with high-risk BRCA mutations do not pursue assistance of an expert panel of clinical genetics service risk-reducing surgery. Studies indicate women are fully providers. The outcome of this project will be a preliminary informed of risk and benefits but overestimate the benefit measure that assesses family communication of genetic of CRRM as they struggle to synthesis the information they information. Students will develop skills in literature are given; conflating issues such as BC recurrence with review, ethical conduct of research, development of PROMs, second primary BC risk. Asking women to determine their and experience using the Delphi technique. personal values when making decisions has been shown to improve decision-making and reduce decisional regret. Key Words: Genetic information; family communication; genetic counselling; at-risk family members; patient This proposal will develop an on-line tool which integrates reported outcomes. state-of-the-art genome-based BC risk prediction (high and moderate risk genes and polygenic risk scores) Target Students: Honours. with evidenced based clinical outcomes through For more information about this project, contact: microsimulation modelling. The tool will allow women to determine their optimal clinical decision based on best Dr. Laura Forrest [email protected] clinical evidence, a personalised BC risk assessment and the clinical outcomes that they personally value and wish to optimise. Aim. To facilitate evidence– and personal values -based decision-making in women contemplating risk-reducing BC surgery.

41 WHY STUDY AT PETER MAC? WORDS FROM OUR CURRENT AND RECENT RESEARCH STUDENTS

We are proud to offer a supportive and nurturing environment for our students throughout their degrees. Our researchers mentor and support our students throughout their research and towards their careers. Our student committee provides peer-to-peer mentoring opportunities through scientific and social events including an annual retreat and our annual student symposium.

“Peter Mac is a very stimulating environment with such a wide array of cancer research being completed here, to an international standard. I’m so excited to be at one of the top-class research institutes in Australia and I’m looking forward to the adventures ahead.” Rosie completed her honours at Peter Mac in 2012. The cohort of honours students that year was a very tight-knit group who all helped each other throughout the course. The community of researchers, from Lab Heads to Research Assistants, also guided them through and this is one of the main reasons Rosie returned to Peter Mac for her PhD. Rosie made important contributions to Peter Mac duurng her PhD: President, Postgraduate Student Society (2016); Chair, Postgraduate Student Society (2017); invited guest at the ‘Women in Science Think Tank’ at Government House for International Women’s Day (2017); member of the Peter Mac Education and Training Committee (2017). Rosemary Millen: Commencing her Postdoctoral research position at Hubrecht Institute, Utrecht, Netherlands.

“The Peter MacCallum Cancer Centre is an excellent environment to conduct research because of its connections between the laboratory bench and the clinic. This important link gives me a sense that one day, my findings may be used to actually enhance human health and well being.” Katie completed her Masters in Neuroscience at The University of Melbourne in 2016 and decided to take the leap into cancer research for her PhD. She was attracted to the Peter Mac because of its reputation as a world leader in cancer research and its partnerships with other leading institutes. It is through a collaboration with The Walter and Eliza Hall that Katie is able to use cutting edge single-cell technology to investigate heterogeneity in acute myeloid leukaemia.

Katie Fennell: PhD student, Dawson Laboratory. Recipient of a Melbourne International Research Scholarship; Member, 2017 Postgraduate Student Committee.

“I was fascinated by the innovative ideas and research quality of Peter Mac labs publications. I was convinced that I could make a significant impact on the field by joining the Peter Mac and contributing to cancer research - the ultimate frontier. Today, my project supervisory team brings together significant combined expertise in subject areas relevant to my research and the Peter Mac state of the art facilities, sequencers and computing clusters empower me to achieve my goals.” Luis completed his Master of Bioinformatics at The University of Melbourne, conducting his research placement at Peter Mac. He commenced his PhD in 2016, attracted to Peter Mac by the multidisciplinary projects and supervisory teams offered in their programs. Luis Lara-Gonzalez: PhD Student, Goode Laboratory. Recipient of a Melbourne International Research Scholarship, a Cancer Therapeutics Top-up Scholarship. President of the Postgraduate Student Society, 2017.

Peter MacCallum Cancer Centre 42 “My very first impression of Peter Mac was how there is a well-structured education and recruitment program for students, described on the website. It’s very important and also encouraging to have project outlines, so students from the other side of the world know what people are currently doing and, more importantly, which researchers are recruiting students here.” Jirawas came to Australia to undertake a project targeting ribosome biogenesis in acute myeloid leukaemia. She was a recipient of an International Postgraduate Research Scholarship & Cancer Therapeutics Top-up Scholarship, and was President of the Postgraduate Student Society, 2015. Following completion of her PhD in 2018, Jirawas movedundertook a postdoctoral researcher position at the Centre for Genomic Integrity, South Korea. She then moved into industry, commencing a position as R&D Scientist in cancer diagnostic device development with In Vitro Diagnostic (IVD) in South Korea. Dr. Jirawas Sornkom: R&D Scientist with In Vitro Diagnostic (IVD), South Korea.

“Being able to conduct research alongside leading clinicians in the field of familial cancer is an invaluable aspect to my research. Having the opportunity to share research ideas with various active health professionals on a regular basis enables my research to have real impact on current practice. Daily interactions with patients attending the Familial Cancer Centre encourages me to understand the link between clinical research and how it impacts people’s everyday lives.” After completing a Bachelor of Medical Sceince at ANU, Rowan moved into psychosocial research in cacner genetics. He wa attracted to Peter Mac by its outstanding reputation in familial cancer clinical practice and research. Rowan Forbes-Shepherd: PhD Student, Parkville Familial Cancer Centre. Recipient of a Melbourne Research Scholarship; Member, 2017 Postgraduate Student Committee.

“I always wanted to work in translational research and here at Peter Mac I am able to work alongside world-renown oncologists and have the results of my research impact the ongoing treatment of patients and their overall prognosis. It’s a thrilling and stimulating environment to work in, but Peter Mac has provided endless support and encouragement for me to continue on with my research and now undertake my PhD.”

Courtney started at Peter Mac as a summer student, then completed her Honours and Master of Biomedical Science projects at Peter Mac before commencing her PhD in 2017, investigating endocrine resistance in estrogen receptor positive metastatic breast cancer. Courtney Van Geelan: PhD Student, Loi Laboratory. Recipient of a Research Training Program (RTP)-Domestic Schoalrship

“What drew me to Peter Mac was the opportunity to join a dedicated team of researchers and clinicians focused on improving cancer outcomes for patients. Being at the forefront of research into fundamental cancer biology in pursuit of developing new approaches to treat cancer has been an incredibly enriching experience. The unique culture of inter-institue collaboration empowers our ability to translate research findings directly into the clinic” Kenji first came to Peter Mac for an undergraduate project, stayed as a research assistant and Summer student, and then completed his Biomedical Science Honours project at Peter Mac. He commenced his PhD in 2018, developing novel strategies to target mutant-p53 cancers. Kenji Fujihama: PhD Student, Clemons Lab. Recipient of a Research Training Program (RTP)-Domestic Scholarship; Member, 2018 Postgraduate Student Committee; President, 2019 EMBL Australia Postgraduate Symposium Committee.

43 Peter MacCallum Cancer Centre 305 Grattan Street Melbourne Victoria 3000 Australia Locked Bag 1 A’Beckett Street Victoria 8006 Australia www.petermac.org Follow us on Twitter @PeterMacCC For more information, please contact:

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Peter MacCallum Cancer Centre 44