My overall aims are to improve outcomes for cancer patients and contribute to a dynamic translational and clinical research community. As a physician–scientist, I have longstanding experience in the clinical application of novel immunotherapies for the treatment of melanoma.
I have led numerous Phase I and II clinical trials across a broad portfolio of clinical and translational projects involving cytokines, peptide and protein vaccines, as well as targeted therapies including development of BRAF and MEK inhibitors. Over 20 years I have developed integrated clinical and laboratory teams focused on understanding immune responses against cancer and exploring new cancer therapies based on this knowledge. More recently, new insights into tumor resistance have shown that it is also critical to understand the biology of cancer plasticity to counter the mechanisms that underpin escape from immune control. My research brings these elements together with the intention of achieving greater clinical benefit.
My investigations and collaborations have resulted in more than 150 clinical and translational publications with a focus on melanoma cell biology and immunology, many invited reviews and eight patents. In addition to my clinical and research interests, I am actively involved in training and mentoring of Medical Oncology Advanced Trainees, Clinical Research Fellows, postdoctorals and postgraduate research students.
Director, Ludwig Melbourne
Laboratory Head, Cancer Immunobiology Laboratory
Professor, University of Melbourne, Department of Medicine
Director, Cancer, Spinal and Outpatients, Clinical Services Unit, Austin Health
MBBS (Hons), University of Melbourne, Australia
Fellowship of the Royal Australasian College of Physicians, specialising in Medical Oncology
PhD, University of Melbourne. Thesis Title: Characterisation and Pharmacokinetics of Granulocyte-Macrophage Colony-Stimulating Factor
NH&MRC Practitioner Fellowship, National Health & Medical Research Council, Australia, 2008
Level 5, Olivia Newton-John Cancer & Wellness Centre, Austin Health, 145-163 Studley Road
We integrate fundamental laboratory research with translational and clinical studies. Our scientists are exploring three cancer treatment approaches: cancer vaccines, targeted antibodies and small-molecule inhibitors. These methods are designed to prevent the growth of tumors and the spread of cancer without the dangerous and unpleasant side-effects of current cancer therapies.
Level 5, Olivia Newton-John Cancer & Wellness Centre, Austin Health, 145-163 Studley Road
Click the links below for more information on the world-class capabilities of Ludwig Melbourne.
This facility that can produce small (mg) to large amounts (gms) of high-quality recombinant proteins and antibodies for use in medical research.
• Cell line development
• Biologics production
• Protein purification
• Protein analysis
• Protein characterization
Cell line development
Transient expression, stable expression, and isolation/enrichment of high-producing clones can be performed in mammalian cells.
A range of production systems are available depending on the scale required. Perfusion systems can produce material every two days ranging from tens of milligrams to several hundred milligrams per harvest. A proprietary biphasic approach to production is used during cell culture in stirred tank bioreactors to increase yields and improve protein quality. Culture volumes from 400 mL to 10L are available in shake flasks and from 2L to 15L in a stirred-tank bioreactor. Yields up to 4g/L of monoclonal antibody in a GS CHO cell line have been achieved.
Purification and product characterisation
Production material is purified using a variety of chromatography techniques such as affinity, size exclusion and ion exchange. Operating procedures allow for flexibility to process materials ranging from milligrams to several grams. Quality assessments are conducted through a combination of SDS-PAGE and size-exclusion chromatography. Potency assessments for antibodies can include binding to target antigen by FACS or biosensor assessments.
Established through a $2 million grant from the Australian Cancer Research Foundation, the Centre specializes in:
PET MRI IMAGING
By combining a high-performing PET system and compact MRI technology, NanoScan® PM PET/MRI provides preclinical, whole-body soft tissue images with detailed quantitative imaging data within just one study. The PET camera offers quantitative 3D spatial resolution at 700 µm, combined with uniquely large field-of-view. The 1 Tesla permanent magnet for MRI provides 100 µm resolution with advanced sequences and ensures robust imaging across a broad range of biological applications, including:
• Tumor biology
• Stem-cell investigations
• Regenerative medicine
• Neuroscience and receptor studies
• PET development of radiotracers
• Immunology, inflammation
• Multimodal contrast agent development
• Animal model development and phenotyping
SPECT CT IMAGING
The NanoSPECT/CTTM is an in vivo molecular imaging system suitable for use with small animals and unifies functional (SPECT) and anatomical (CT) imaging procedures for preclinical investigations. With 250μm 3D SPECT and 30μm CT spatial resolution, exceptional image quantification is permitted with an accuracy of more than 97%.
The system enables the examination of bio-chemical processes in healthy and disease models (e.g., cancer, diabetes, stroke), determining the localization of the radio-labeled compounds utilized as probes for the disease state, and monitoring the efficacy of interventions or administered therapies. In living subjects, the effect of candidate drugs in development can be monitored and compared in a real-time aspect at multiple time points within the one subject, while drug localization as well as uptake can be quantified and visualized from the data collected. The system is also suitable for monitoring genetic modifications and gene-therapeutic healing procedures using appropriate preclinical models.
IVIS SPECTRUM BIOLUMINESCENT AND FLUORESCENSE IMAGING
The IVIS® Spectrum is a versatile and advanced in vivo imaging system that uses a novel patented optical imaging technology to facilitate non-invasive longitudinal monitoring of disease progression, cell trafficking and gene expression patterns in living animals. An optimized set of high-efficiency filters and spectral un-mixing algorithms enables a researcher take full advantage of bioluminescent and fluorescent reporters across the blue to near-infrared wavelength region. It also offers single-view 3D tomography for fluorescent and bioluminescent reporters that can be analyzed in an anatomical context using a Digital Mouse Atlas or registered with the IVIS multi-modality module to other tomographic technologies such as MR, CT or PET.
For advanced fluorescence pre-clinical imaging, the IVIS Spectrum can use either trans-illumination (from the bottom) or epi-illumination (from the top) to illuminate in vivo fluorescent sources. 3D diffuse fluorescence tomography can be performed to determine source localization and concentration using the combination of structured light and trans illumination fluorescent images. The instrument is equipped with 10 narrow band excitation filters (30nm bandwidth) and 18 narrow band emission filters (20nm bandwidth) that assist in significantly reducing autofluorescence by the spectral scanning of filters and the use of spectral unmixing algorithms. In addition, the spectral unmixing tools allow the researcher to separate signals from multiple fluorescent reporters within the same animal.
For access information please contact:
ACRF Centre Project Manager
For assistance in designing your project or information on radiotracers required for your imaging, please contact:
Principal Medical Physicist
Ludwig Melbourne invites applications from highly motivated and creative individuals to undertake PhD, BSc (Hons), BMed Sci and DMed Sci degrees. Ludwig is affiliated with the University of Melbourne, and students enroll in the Department of Medicine. Ludwig attracts students from a wide range of disciplines—biochemistry, genetics, immunology, medicine, microbiology, pathology and physiology.
We are committed to providing post-graduate students with an environment in which to excel in cancer research and make original discoveries that will improve the understanding and treatment of cancer. Ludwig provides state-of-the-art facilities and world-class scientists and medical specialists to guide young researchers. To further support the next leaders in the fight against cancer, we offer these additional benefits worth up to AUD $20,000:
• Funding to attend an overseas conference
• Funding to attend local/national conferences
• Personal laptop
• Reimbursement of student union fees
• Six-month stipend, beyond scholarship
• Thesis writing support
For general student queries on postgraduate study at the Ludwig Melbourne, please contact the Postgraduate Student Advisor, A/Prof John Mariadason at +613 9496 3068 or e-mail here.
The Melbourne-Austin Branch does not offer placements to secondary school students for work experience. Please e-mail our HR manager for more information.
Click the links below to read more about our current postgraduate projects.
Every week, 70 Australians die of colorectal cancer, mainly because of a lack of treatment options for patients with late-stage disease. Our laboratory investigates novel and innovative therapies for the treatment of colorectal cancer and has extensive pre-clinical and translational experience working with targeted therapeutics. A novel family of molecular compounds that have recently demonstrated strong anti-tumor efficacy in pre-clinical models of hematological cancers are bromodomain inhibitors. These compounds inhibit a subset of chromatin-binding proteins that contain a bromodomain. These proteins regulate the transcription of growth-promoting genes, including c-myc. Consequently, blocking the activity of these proteins results in the inhibition of tumor cell growth. The aim of this honors thesis is to evaluate the efficacy of bromodomain inhibitors in colorectal cancer cell lines, and to identify molecular biomarkers that predict response to these drugs. Findings from these studies will help determine whether these drugs represent a novel treatment option for patients with colorectal cancer. The project will provide the student with exposure to fundamental concepts in cancer biology and familiarity with key cell and molecular biology techniques, including tissue culture, cell proliferation assays (MTS), DNA transfection, gene knockdown by siRNA, Western Blot and gene expression profiling by quantitative RT-PCR.
Filippakopoulos P, Qi J, Picaud S, Shen Y, etal Selective inhibition of BET bromodomains. Nature 468(7327):1067-73, 2010.
Nicodeme E, Jeffrey KL, Schaefer U, et. al. Suppression of inflammation by synthetic histone mimic. Nature 468(7327):1119-23, 2010.
The treatment of EGFR/ERBB1- and ERBB2-expressing breast (as well as many other) cancers, with monoclonal antibodies has become one of the foundations of modern oncology practice, however not all patients respond to treatment, and resistance invariably develops. This project aims to assess whether established as well as novel ERBB therapeutics developed in this laboratory can be rationally combined to target not only ERBB signalling, but also metabolic pathways. EGFR activation triggers intracellular signalling through the RAS/RAF mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR axis. In addition to its better-known functions in promoting protein synthesis and suppressing autophagy, the PI3K pathway has emerged as a key regulator of cellular metabolism. Recent studies have found that mTOR activation is sufficient to stimulate an increase in glucose uptake, glycolysis, and de novo lipid biosynthesis, which are considered metabolic hallmarks of cancer, and administration of PI3K/Akt/mTOR pathway inhibitors has been associated with metabolic toxicities of hyperlipidemia and hyperglycemia. Given that PI3K is frequently mutated in breast cancer and anti-PI3K agents and anti-EGFR therapeutics are already in use in the breast cancer clinic, this intriguing and complex interplay between signalling downstream of EGFR and a cancer cell’s control of metabolic pathways via mTOR activation will be examined. The project will provide the student with exposure to fundamental concepts in cancer cell signalling and familiarity with key in vitro cell and molecular biology techniques, including tissue culture, cell proliferation assays (MTS), apoptosis analyses, SDS-PAGE and Western blots. Investigations may also be conducted using in vivo xenograft models.
Identifying T cell responses to melanoma using cells loaded with tumour antigen expressing bacteria.
T cells immune responses to melanoma antigens are found in many patients, either occurring spontaneously or induced following immunotherapeutic vaccination.
This project aims to set up a novel system to identify which melanoma antigens patients respond to. The intracellular bacterium Listeria monocytogenes will be used to establish a system where melanoma antigens can be expressed at high levels within patient cells1. These antigen over-expressing cells may be used to test T cells from the same patient, and identify which melanoma proteins they respond to.
In this way we can develop our knowledge of how the immune system responds to melanoma in patients treated in various ways, and identify which melanoma antigens may be the best targets for immune interventions.
1 - Higgins et al Molecular Microbiology (1999) 31(6), 1631–1641
Click the links below for news, reports, events and information about our partners in cancer research.
Ludwig discovery leads to Australian patient trials
February 1, 2012
Previous scientific reports:
Monday, August 5, noon
The connection between lymphangiogenic signalling and prostaglandins: a missing link in cancer metastasis
Associate Professor Steven Stacker
Peter MacCallum Cancer Centre
Monday, August 12, noon
High throughput RNAi and miRNA screening strategies for functional gene analysis
Dr. Kaylene Simpson, head of the Victorian Centre for Functional Genomics
Peter MacCallum Cancer Centre
Monday, August 19, noon
Dr. Michael Buchert, Walter & Eliza Hall Institute
Monday, August 26, noon
Dr. Michael Michael, head of the Gene Expression Laboratory, Flinders University, Adelaide
Ludwig Melbourne would like to thank the Australian Cancer Research Foundation for its significant funding to establish the state-of-the-art ACRF Centre for Translational Cancer Therapeutics and Imaging. The facility will benefit Australian cancer patients by significantly increasing the understanding of the underlying causes of cancer while exploring new approaches to treatment.
Ludwig Melbourne has received $98,000 for molecular imaging radiochemistry equipment from the Percy Baxter Charitable Trust, managed by Perpetual.