Sam Faulkner, Nathan Griffin, Xiang Li, Alison Rutledge
The group works on the crosstalk between nerves and cancer cells, and the impact on tumour progression.
Until recently it was thought that neurons were not actively involved in cancer. However, recent evidence in prostate and breast cancers, including from our group, have shown that nerves promote tumour progression and that denervation can suppress both the development of the primary tumour and the outburst of metastases.
The objective of the group’s research is to identify the molecular mediators of the crosstalk between nerve and cancer cells, which constitute new and innovative biomarkers and therapeutic targets in oncology.
The methodologies used include analysis of human tumour samples, cell cultures, in vivo experiments and proteomic analysis.
The group work in collaboration with neurobiologists, pathologists, clinicians and private companies to translate the results of the research into practical outcomes in oncology.
Nerve-cancer cell crosstalk. Nerves infiltrate solid tumours and stimulate cancer growth and metastasis through the liberation of neurotransmitters.
Conversely, nerve infiltration in the tumour is mediated through the liberation of neurotrophic growth factors by cancer cells. Neurotransmitters and neurotrophic growth factors also impact angiogenesis and inflammation.
This reciprocal interaction fuels cancer development, and participates in cancer pain.
Lin Kooi Ong
A. R. Satvik Iyengar
The focus of the group’s work has been the enzyme tyrosine hydroxylase which controls the rate of synthesis of the catecholamines dopamine, noradrenaline and adrenaline.
They have examined the role of regulation of tyrosine hydroxylase in response to different types of stress.
Their work is now focused on how regulation of tyrosine hydroxylase plays a role in Parkinson's disease.
They found that there is a selective loss of one of the human TH isoforms in Parkinson's disease and that expression of particular TH isoforms may render the cells more susceptible to death in Parkinson's disease.
Current work has focused on the role of infection and inflammation in the development and progression of Parkinson’s disease.
They found that there is a chronic activation of tyrosine hydroxylase in response to infection that only occurs in the dopaminergic neurons of the substantia nigra.
They also found that the response to infection in females is substantially reduced when compared to males.
This may explain the capacity of infection processes to cause selective degeneration of the dopaminergic neurons of the substantia nigra and the increased susceptibility of males that are key features of Parkinson’s disease.
The research area is the molecular mechanisms responsible for regulating neuronal function during development, plasticity and ischaemic/excitotoxic damage.
The main research focus is on the role and regulation of the important regulatory enzyme CaMKII.
The group have identified a new mechanism (autophosphorylation of CaMKII at T253) that controls the function of CaMKII in vivo through molecular targeting.
The group have shown that this mechanism regulates cell proliferation and is selectively activated in brain tissue by ischaemia and excitotoxity.
The current research explores the mechanisms by which this new regulatory mechanism controls cell death in the brain following stroke and the therapeutic potential of drugs that interfere with this regulatory mechanism.
Yuan Yuan Zhang
Yuan Yuan Zhang
Hessam Tabatabaeehatambakhsh, Jennifer Latham, Simonne Sherwin, Amanda Croft
Xu Guang Yan
Hessam Tabatabaeehatambakhsh, Yu Chen Feng, Xiao Hong Zhao
Man Ya Wu, Lin Shi Zhang
Melanoma is the most serious form of skin cancer that is often referred to as Australia's national cancer as Australia has the highest incidence of melanoma in the world.
However, there is currently no curative treatment once the disease spreads beyond the original site.
To address this major Australian health problem, the laboratory has been working on translational melanoma research with a focused theme of “overcoming resistance of metastatic melanoma to treatment”.
Specifically, the group are working on overcoming resistance of melanoma cells to programmed cell death induced by newly developed targeted therapeutic drugs and immunotherapeutic agents.
The group have initiated a number of new projects that advance the frontier of melanoma research.
These include “apoptosis-regulating long non-coding RNAs in melanoma”, “targeting resistance mechanisms of quiescent melanoma cells to programmed cell death”, “co-targeting CD47 and the MAPK pathway or PD-1/PD-L1 in the treatment of melanoma”, and “regulation of immune checkpoints in melanoma”.
Sharon Hollins, Joshua Atkins, Michael Geaghan, Ebrahim Mahmoudi, Dylan Kiltchewskij-Brown
The human brain is by far the most complex of organs, with around 100 billion neurons interconnected by up to 1000 trillion synapses.
During development, the formation, position and connectivity of these cells is precisely regulated and yet remain responsive to external sensory input and output from internal processing.
The group is interested in understanding the molecular systems that regulate neural development and synaptic plasticity so they can identify the underlying molecules and mechanisms that orchestrate the formation and behaviour of neural circuits.
These circuits provide the physiological basis of neural activity-associated logic, and their structure and plasticity is the foundation for a life-long capacity for learning and cognition.
These systems are sensitive to genetic and environmental influences, and a complex combination of these neurodevelopmental challenges can lead to neurocognitive and neuropsychiatric disorders such as schizophrenia.
By investigating the molecular neurobiology of these complex systems, and the syndromes that interfere with their normal function, the group has the potential to better understand human brain development and function.
These steps also provide a strong basis for developing biomarkers of brain disease and novel therapeutic strategies to defeat the most devastating neurocognitive disorders.
In 2015 the group made important methodological and theoretical advances that support their investigation of the complex systems biology of neurodevelopment, synaptic function and schizophrenia.
To explore the role of schizophrenia-associated miRNA in vivo the group have successfully implemented lentiviral transduction of the rat brain (collaboration with Chris Dayas and Rohan Walker) and observed schizophrenia-related neurobehavioural phenotypes.
They have also been developing a framework for high-resolution translational genomics using whole genome sequencing and applying this for personalised analysis of schizophrenia patients using integrated systems biology.
This research has made spectacular progress through the support of a NSW Health Collaborative Genomics Grant ($800,000), which enabled the group to sequence the entire genome of 500 participants in the Australian Schizophrenia Research Bank.
Further refinement in their understanding of the function of non-coding variants is being achieved through the development of isogenic cell lines produced through RNA-guided genome editing using the Cas9/CRISPR approach.
Support for this initiative was obtained from the US Brain and Behavioural Research Foundation, Independent Investigator Grant (US $100,000).
Ritambhara Aryal, Mohitosh Biswas, Nilofar Daneshi, Kristy Martin, Al Shahandeh, Jason Woods, Khadem Ali (co-sup.)
Melissa Baldwin, Cassandra Bower, Sam Gerami, Ryan Horn, Will Myles
The laboratory research applies omics and bioinformatics as well as more traditional cellular, molecular and functional approaches to understand central nervous system health and disease.
The group have had two major papers accepted on iron-myelin interactions in brain degenerative and psychiatric conditions following requests to collaborate on projects by researchers from University College London and UK Brain Expression Consortium.
The group are also working with pharmacy and other academics and industry stakeholders to align research and education for responsible delivery of precision medicine in healthcare practice.
A/Professor Milward attended two advisory group meetings for the US NIH Precision Medicine Initiative (Nashville; Intel, San Francisco) and chaired the ‘Big Data, Personal Genomics and Bioinformatics’ stream of the Global Precision Medicine Congress, London, September 2015.
In 2015 the laboratory had 1 PhD completion (Moones Heidari), 5 confirmations (Ali, Aryal, Biswas, Martin, Shahandeh) and new PhD student Jason Woods was awarded a Vice Chancellor’s Excellence Scholarship. Moones Heidari won the School Paper of the Year award and Ritu Aryal, Moones Heidari and Jason Woods all received Beautiful Science awards.
In 2015, the group had 8 papers and 1 encyclopaedia chapter accepted for publication with 3 international presentations (Milward University College London and University of Warwick, UK; Shahandeh, International BioIron Society, Hangzhou, China) and 20 posters at 1 international and 4 national conferences.
Muhammad Jamaluddin, Arnab Ghosh, Manish Kumar Jhamb, Shafiq Syed
Lisa Sercombe, Yazmin Crossingham, Isabella Moore, Varshini D. Venkata, Yohannes K. Emiru, Fatemeh Hashemi, Aminah Ali Abid Al-Juboori
The major focus of the group’s research program is to develop early detection tests and new treatments of gynaecological diseases including ovarian and endometrial cancers.
The group are using genetically modified preclinical models, cancer patient derived xenograft models and primary human tissue samples to define the molecular and cellular events involved in pathogenesis and then using this knowledge to develop targeted therapies to improve clinical outcomes in human patients.
The current research focuses on:
- Early detection tests for gynaecological diseases
- Role of microenvironment in ovarian and uterine cancers
- Wnt-P13K-mTOR signalling axis in ovarian and uterine cancers
- Cancer stem cells in ovarian and uterine cancers
- Pathogenesis of endometriosis
This work showed that loss of tumour suppressor genes guarding the mTOR pathway occurs, at both genomic and protein level, in ~60% of human serous ovarian cancer patients and similar alterations in mice also causes the development of serous ovarian cancer.
Lachlan Schofield, Cheenie Nieva, Chrissy Miller
The Cancer Cell Biology Group is part of the University of Newcastle’s Priority Research Centre for Cancer Research, Innovation and Translation, The Hunter Medical Research Institute Cancer Research Program and The Hunter Cancer Research Alliance.
The research primarily focuses on unravelling the mechanisms underpinning cancer cell proliferation, survival, and metastasis, with a view to developing new anti-cancer therapies that target these mechanisms that are less toxic than existing treatments.
In recent years, the group has identified several novel targets and therapeutic inhibitors that are effective in a range of cancer types, including acute myeloid leukaemia and childhood acute lymphoblastic leukaemia, brain and breast cancers.
In addition to the group’s drug discovery interests, they use a variety of proteomic and molecular techniques to identify novel biomarkers that can be used for the improved treatment of leukaemias, brain, and breast cancers, so that a more personalised approach for cancer treatment can be developed.
Richard Kahl, Hayley Flanagan
Heather Murray, David Skerrett-Bryne, Abdul Mannan, Dr Jon Sillar, Nikita Panicker
The Molecular Oncology Group is part of The University of Newcastle’s Priority Research Centre for Cancer Research, Innovation and Translation, The Hunter Medical Research Institute Cancer Research Program and The Hunter Cancer Research Alliance.
The group also collaborate closely with the Human Genetics Department, KU Leuven and the Department of Biochemistry and Molecular Biology, University of Southern Denmark.
The research focuses on the molecular basis of cancer development, progression and chemotherapy resistance through the development of sophisticated in vitro and in vivo cancer model systems and world leading technologies.
The research program utilises both targeted (targeting tumour suppressor proteins, cellular metabolism and DNA damage) and non-targeted (unbiased comparative and quantitative proteomics) approaches.
The group employ high resolution techniques to complement these approaches such as multiplexed targeted proteomics (parallel reaction monitoring (PRM)), targeted next generation sequencing (NGS), and drug development pipelines incorporating advanced proteogenomic technologies.
In 2015 Dr Matt Dun was elected to the board of directors of the Australian Society for Medical Research, where he now sits as the National Media Director.
CANCER SIGNALLING RESEARCH GROUP
Dr Matt Dun – Senior Lecturer
Dr Ryan Duchatel
Dr Ameha Woldu
Dr Abdul Mannan
Ms Alicia Douglas
Ms Evangeline Jackson
Zacary Germon, Dilana Staudt Barreto, Farjana Afrin, Tabitha McLachlan, Dr Jonathan Sillar, Dr Tiffany Gould, Evangeline Jackson.
The survival of children diagnosed with cancer has dramatically improved over the last 10 years. However, for children diagnosed with high-risk acute myeloid leukaemia (AML) survival remains less than <45%, and for children diagnosed with diffuse intrinsic pontine glioma (DIPG) there is no effective adjuvant pharmacological or immunological treatment and survival remains less than a year. In Australia each year, 101 children under the age of 15 die each from cancer. Although AML and DIPG are rare, together they account for 30% of all deaths. Recurring mutations that drive the activity of signalling proteins are overarching contributors to disease progression in both AML and DIPG, therefore, the Cancer Signalling Research Group (CSRG) investigates which of these dysregulated signalling pathways are the best to target using the plethora of well-tolerated FDA approved drugs repositioned from other indications, as well as testing the efficacy of emerging experimental drugs. Employing complementary cell and molecular biology techniques, coupled with a program of high-resolution, quantitative proteomics the CSRG utilises clinically relevant cancer models and primary patient samples to reveal mechanisms driving cancer cell growth, survival and, the factors determining a cancer’s susceptibility or resistance to particular drug therapy.
Led by internationally trained, biomedical scientist Dr Matt Dun (NHMRC Investigator 2020-2025, Defeat DIPG ChadTough New Investigator 2020-2021), and thanks to industry, commercial and philanthropic supporters, the CSRG’s current works fall under the following research themes:
- Improving outcomes for high-risk paediatric cancers
- Discovering treatment targets for high grade brain cancer
- Investigating medicinal cannabis for the treatment of brain and blood cancers
- Repurposing available drugs for the treatment of childhood brain cancer
- Developing treatments for relapsed and treatment resistant acute myeloid leukaemia
- Developing novel monitoring techniques for blood, brain and colorectal cancers
CURRENT PROJECT FUNDING:
$627K NHMRC New Investigator 2020-2024
$360K Defeat DIPG ChadTough New Investigator 2020-2021
$328K Charlie Teo Foundation Alegra’s Army Fellowship 2020-2022
$103K Tour de Cure Pioneering Research Grant 2020
$100K Fight on the Beaches Project Funding 2020
$26K Hunter Children’s Research Foundation Kids’ Cancer Grant
$25K McDonald Jones Charitable Foundation
$16K Kiriwina Investment Company Project Funding
PUBLICATIONS LAST 12 MONTHS:
Dun MD, Rigby CJT, H. D., Butler S, Sillar J, Duchatel RJ, Germon ZF, Chi M., Mannan AS-B, Murray HC, Kahl R, Flanagan H, Almazi JG, Nixon B, De Iuliis GN, de Bock C, Alvaro F, Morris JC, Enjeti AK, Verrills NM. Shwachman-Bodian-Diamond syndrome (SBDS) protein is a direct inhibitor of protein phosphatase 2A (PP2A) activity and negative prognostic marker in acute myeloid leukemia. Leukamia (Resubmission, under consideration). Impact factor 9.944
Cafe SL, Nixon B, Dun MD, Roman SD, Bernstein IR, Bromfield EG. (2019) Oxidative stress dysregulates protein homeostasis within the male germ line. Antioxidants and Redox Signaling. Impact factor: 5.828
Zhou W, Stanger SJ, Anderson AL, Bernstein IR, De Iuliis GN, McCluskey A, McLaughlin EA, Dun MD, Nixon B. (2019) Mechanisms of tethering and cargo transfer during epididymosome-sperm interactions. BMC Biology.17:35. Impact factor: 6.7
Sillar JR, Germon ZP, De Iuliis GN, Dun MD. (2019) The Role of Reactive Oxygen Species in Acute Myeloid Leukaemia. International Journal of Molecular Sciences. 20:6003. Impact factor: 4.2
Nixon B, Johnston SD, Skerrett-Byrne DA, Anderson AL, Stanger SJ, Bromfield EG, Martin JH, Hansbro PM, Dun MD. (2019) Modification of Crocodile Spermatozoa Refutes the Tenet That Post-testicular Sperm Maturation Is Restricted To Mammals. Molecular & Cellular Proteomics. 18:S59-s76. Impact factor: 4.828
Petit J, Carroll G, Gould T, Pockney P, Dun MD, Scott RJ. (2019) Cell-free DNA as a diagnostic blood-based biomarker for colorectal cancer: a systematic review. Journal of Surgical Research. 236, 184-197. Impact factor: 1.9
Nixon B, De Iuliis GN, Hart HM, Zhou W, Mathe A, Bernstein IR, Anderson AL, Stanger SJ, Skerrett-Byrne DA, Jamaluddin MFB, Almazi JG, Bromfield EG, Larsen MR, Dun MD. (2019) Proteomic Profiling of Mouse Epididymosomes Reveals their Contributions to Post-testicular Sperm Maturation. Molecular & Cellular Proteomics.18:S91-S108. Impact factor: 4.828
Nixon B, De Iuliis GN, Dun MD, Zhou W, Trigg NA, Eamens AL. Profiling of epididymal small non-protein-coding RNAs. (2019) Andrology. Impact factor 3.106
Duchatel RJ, Jackson ER, Alvaro F, Nixon B, Hondermarck H, Dun MD. (2019) Signal Transduction in Diffuse Intrinsic Pontine Glioma. Proteomics. e1800479. Impact factor 3.106
Bromfield EG, Walters JLH, Cafe SL, Bernstein IR, Stanger SJ, Anderson AL, Aitken RJ, McLaughlin EA, Dun MD, Gadella BM, Nixon B. Differential cell death decisions in the testis: evidence for an exclusive window of ferroptosis in round spermatids. (2019) Molecular Human Reproduction. 25:241-56. Impact factor 3.4
Nixon B, Bernstein I, Café SL, Delehedde M, Sergeant N, Eamens AL, Lord T, Dun MD, De Iuliis GN, Bromfield EG. (2019) A Kinase Anchor Protein 4 is vulnerable to oxidative adduction in male germ cells. Frontiers in Cell and Developmental Biology. Impact factor 5.206
Brendan Scott, Chris Stevens, Andrew Novak
Recent research has been focused on the emerging use of mHealth and eHealth strategies to increase the effectiveness of the management and treatment of Chronic Diseases such as Type 2 Diabetes and Juvenile Idiopathic Arthritis. As a founding member of the Chronic Disease eHealth Research Group, Dr Sculley has been involved in the development of an integrated approach to disease care, including the use of mobile technology in conjunction with a dedicated mobile app - Integrated Clinics - that will greatly increase the monitoring, management and treatment of disease. Dr Sculley is also actively involved in the management and treatment of Periodontal Disease, currently focussing on gene polymorphisms and epigenetic modifications and their impact on disease status.
Danielle Bond, Crystal Naudin, Joshua Brzozowski, Helen Jankowski
Benjamin Munro (PhD), Michelle Barnett (PhD)
The research focus is on improving cancer patient outcomes and quality of life.
The research seeks to achieve this by unravelling the role of extracellular vesicles in the process of metastasis.
Through characterising the make-up of these extracellular vesicles the group hope to identify a biomarker as well as a means to target the delivery of current chemotherapeutics specifically to cancer cells.
In collaboration with other local, national and international researchers they are also searching for more effective anti-cancer agents that are hidden within a biodiverse range of organisms.
- Identify a molecule within human body fluids that can predict disease and/or disease outcome for cancer patients
- Improve patient quality of life through the generation of targeted delivery of treatment and the development of novel treatments for cancer patients
- Understand the role of cancer extracellular vesicles in haemostasis and how this influences patient outcome