Centre for Cancer Biology

Centre for Cancer Biology

The major aim of the “Centre for Cancer Biology” (CCB) is to pursue a culture of scientific excellence and innovation to understand the fundamental basis of cancer with the goal of developing better treatment strategies.

Strengths:

• The CCB has a critical mass and an international track record in cancer biology research.
• The members of the CCB are already co-located with infrastructure in place.
• The Members of the CCB have complementary expertise that allows a multi-disciplinary approach essential for success in a highly competitive environment.
• The Members of the CCB bring in significant funding from peer-reviewed funding agencies and from commercial partners.

Directors: Professors Angel Lopez and Sharad Kumar

Faculty Membership: Dr Claudine Bonder, A/Prof Richard D’Andrea, A/Prof Gregory Goodall, Dr Michele Grimbaldeston, Dr Mark Guthridge, Dr Natasha Harvey, Prof Tim Hughes, Dr Yeesim Khew-Goodall, Prof Junia Melo, Dr Stuart Pitson, and A/Prof Andrew Zannettino

Key Research Areas:

• Identifying and targeting cancer stem cells

One of the major issues with current therapies is the frequent relapse due to failure to destroy the cancer stem cell. Our recent work identified the acute myeloid leukaemia stem cell with our MAb 7G3 which has shown in pre-clinical trials to be effective in this disease. This work offers a roadmap for targeting the malignant stem cell of many cancers. In addition, we are exploiting our expertise on mesenchymal stem cells as a potential source of regenerative therapies.

• Apoptosis and cell survival in cancer

Evasion of apoptosis is a hallmark of tumorigenesis. We have extensive expertise in studying cell death pathways and their role in cancer development. We combine basic biology with in vivo animal models of cancer to understand how aberrations in cell death, cell survival and cell cycle can lead to tumorigenesis.

• Epithelial mesenchymal transition (EMT)

This is a process undergone by many solid tumours and is at the heart of metastasis. We have recently identified the key elements involved in this process that are at work in leukaemia and solid tumours.

• Myeloma research

Multiple myeloma (MM) is an incurable haematological cancer of the antibody-producing plasma cell (PC). MM is unique amongst haematological malignancies in its capacity to cause massive destruction of the skeleton. We have  an extensive ongoing program in identifying the molecular and cellular mechanisms responsible for the bone destruction.

• Abnormal signalling in cancer cells

This is typical of most cancer cells that allows them to evade normal regulatory control mechanisms. We have unique expertise in sphingosine kinase and bcr-abl, two key enzymes involved in the subversion of normal processes in cancer cells . This area will also focus on abnormal cell survival pathways in acute and chronic myeloid leukaemias, a significant problem which is the major stumbling block for long lasting therapies in these types of cancer. We have also recently defined a new paradigm for the regulation of IGF-1 signaling, a key pathway in tumour cells.

• Define how cytokine receptors work

By solving the structure and assembly of these receptors we open new therapeutic opportunities to control their function and effect in cancer cells.

• Develop new drugs for the better treatment of cancer

Our MAb 7G3 against the acute myeloid leukaemia stem cell is now in Phase I clinical trials. Our recent solving of the structure of the GM-CSF receptor shows clear sites for the design of new drugs. Our recent identification of the role of caspases in cancer development in vivo shows a new general target for cancer therapy.

• Oncogenesis and tumour suppression

The transforming ability of oncogenes to initiate and influence solid tumour and leukaemia development is being studied by molecular means and in specialised in vivo mouse models. This area also has significant overlap with cell death/survival studies, given our recent discovery that caspase-2 controls cell cycle following DNA damage and acts as a tumour suppressor.

• Defining  vasculogenesis and lymphangiogenesis pathways

These key processes are subverted in cancer leading to the emergence and spread of solid tumours. Studies in normal organogenesis and in cancer transformation are being conducted to dissect the molecular mechanisms of cancer development and angiogenesis.

• Translational research

By being innovative through the development of new drugs (ie: MAb 7G3) and studious on the effect of externally developed new drugs (ie, imatinib) on our patients we will be improving cancer therapy.

Record of Achievement

Our work is internationally competitive with our team having published in the best international journals such Cell, Nature, Science Signaling, N Eng J Med, Molecular Cell, Nature Cell Biol, J Clin Invest, J Exp Med, J Cell Biol, PNAS, Blood, etc.

The membership of the CCB has a combined output of over 700 publications and over 15,000 citations. We hold a NH&MRC Program Grant, 18 NH&MRC and ARC Project Grants, 3 NH&MRC Fellowships, and several Cancer Council Grants. We also have extensive experience in protecting our inventions through patenting, and importantly, in commercialising them through alliances with the Pharmaceutical industry.

Together we attract >$9 million per annum in research grant funding.

Prof. Angel Lopez, MB BS, PhD, FRCPA

Director, Centre for Cancer Biology

SA Pathology

Professor Angel Lopez obtained his medical degree in 1975 from the University of Rosario, Argentina, and his PhD in 1981 from the University of London. During his post-doctoral work at the Walter & Eliza Hall Institute in 1982-1985, he became interested in the control of inflammation and hemopoiesis by the then newly discovered cytokines and growth factors. In 1985, Angel came to the Institute of Medical & Veterinary Science where he set up the Cytokine Receptor Laboratory and contributed to the establishment of the Hanson Centre for Cancer Research. In 2009, together with Prof S Kumar, he set up the Centre for Cancer Biology in Adelaide.

Angel is the author of 170 research publications and shares his research interests with a group of highly capable and enthusiastic colleagues. The work of Angel and his colleagues has led to significant discoveries in understanding how cytokines and cytokine receptors work in health and in diseases such as leukaemia and asthma. These insights have been possible through funding by the NH&MRC of Australia, NIH of USA and several charitable foundations. His research has been published in high impact medical journals, has been highly cited, and forms the basis of several international patents. This path has underpinned the development of new products with potential therapeutic use in human diseases now in clinical trials.

Angel regularly participates in National Health & Medical Research Council review processes having been part of Program Grant and Discipline Panel Committees. He is Chair of the Organizing Committee of the Barossa Symposia in the “Science Amongst the Vines” biennial series, now in its Fourth edition, and regularly referees for international journals and granting bodies.

His scientific interests continue to be the discovery of paradigms in cytokine receptor biology and the development of new tools and approaches for the better treatment of human diseases.

Prof. Sharad Kumar PhD

Director, Centre for Cancer Biology

SA Pathology

Sharad Kumar is a Senior Principal Research Fellow of the National Health and Medical Research Council (NHMRC) of Australia, a co-Director of the Centre for Cancer Biology at SA Pathology, and an affiliated Professor at the University of Adelaide. He obtained his PhD in Biochemistry from the University of Adelaide (Waite Institute) and worked as a postdoctoral fellow in Brisbane with Martin Lavin. He then moved to the CSIRO Animal Health Laboratory as research scientist before receiving a Japanese Government Science and Technology Fellowship to spend two years as a visiting fellow at RIKEN in Tsukuba, Japan. At the end of this, he took up a position as an Associate Member at the Cancer Institute (Tokyo, Japan), before returning to Adelaide in July 1994.

His laboratory has cloned a number of key regulatory genes, including the developmentally regulated Nedd genes, which include Nedd2 (caspase-2)- the first known apoptotic mammalian caspase, Nedd4 – the first WW-Hect type of ubiquitin-protein ligase, Nedd5 (Sept2)- the first characterised mammalian septin, and Nedd8- a ubiquitin-like protein involved in a protein modification pathway, now widely known as neddylation. The laboratory also cloned a large part of the Drosophila cell death machinery and a number of proteins that regulate the function of Nedd4 ubiquitin ligases. He has published over 160 papers, with >7400 citations and an h index of 50. His laboratory now studies caspase biology and functions in cancer, mechanisms of developmentally programmed cell death, and the physiological functions of the Nedd4 family members.

He is a past Wellcome Fellow and a recently elected foreign member of the European Research Institute for Integrated Cellular Pathology (ERI-ICP). He has served on many peer-review committees, and has chaired the NHMRC Cell Biology and Cancer Biology grant review panels. He is a member of the prestigious Faculty of 1000 (Biology), a receiving editor of Cell Death and Differentiation, and an editorial board member of Open Cell and Developmental Biology Journal, and International Journal of Cell Biology. He was awarded the 2003 ASBMB Amersham Bioscience Award for distinguished achievements in biochemistry and molecular biology research in Australia.