Category Archives: Research Publications

Publication: Automated annotation and visualisation of high-resolution spatial proteomic mass spectrometry imaging data using HIT-MAP

Thomas R. Cox, May 2021

Automated annotation and visualisation of high-resolution spatial proteomic mass spectrometry imaging data using HIT-MAP

Just published in Nature Communications is our new tool for automated annotation and visualisation of MALDI Mass Spec Imaging data.

Spatial proteomics is a powerful tool to directly analyse and map the distribution of proteins in tissues at the single cell scale in an unbiased manner. We have created a new platform to identify and spatially map peptides and proteins that is applicable to a wide scope of applications studying normal and diseased tissues. This technology can be integrated with other established and/or emerging technology platforms (such as spatial transcriptomics) to significantly increase our understanding of health and disease.

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Publication: The Matrix in Cancer

Thomas R. Cox, Feb 2021

The Matrix in Cancer

Just published in Nature Reviews Cancer is the most recent review from the lab on the importance of the extracellular matrix in solid tumours.

Full-text access (view-only) is available via the following SharedIt link

Alterations in the extracellular matrix at the biochemical, biomechanical, architectural and topographilcal levels contribute to the development and progression of solid tumours. Our increased understanding of matrix biology is leading to the development of new approaches that co-target the matrix in cancer, including in metastasis.

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Publication: Targeting Lysyl Oxidase Family Meditated Matrix Cross-Linking as an Anti-Stromal Therapy in Solid Tumours

Thomas R. Cox, Jan 2021

Targeting Lysyl Oxidase Family Meditated Matrix Cross-Linking as an Anti-Stromal Therapy in Solid Tumours

Congratulations to Kaitlin and Yordanos who just had their co-first author review published in Cancers as part of a special edition on Treating the Cancer Matrix: Progress in the Identification of Potential Therapeutic Targets. Also a shout out to Rhiannon for her amazing illustrator skills and creating some beautiful figures. And finally to Jess, who as co-senior author played an instrumental role in bringing everything together.

Extracellular matrix in cancer
Remodeling of the extracellular matrix (ECM) in solid tumours. In healthy tissue, the ECM has a structured basement membrane consisting primarily of collagens IV and VI as well as a scaffolding arrangement of fibrillar collagens that are predominantly secreted by the fibroblasts. In comparison, solid tumours typically consist of more densely packed, aberrantly cross-linked fibrillar collagens resulting from the recruitment and activation of CAFs. As the level of deposition of fibrillar collagens such as collagens I, III and V increases in the tumour ECM, so too does LOX family mediated collagen cross-linking. In addition, tumour ECM results in a breakdown of the structure of the normal basement membrane.
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Publication: The Role of the ECM in Lung Cancer Dormancy and Outgrowth

Thomas R. Cox, Sep 2020

The Role of the ECM in Lung Cancer Dormancy and Outgrowth

We are pleased to report that our recent in depth review on the role of the extracellular matrix (ECM) in Lung cancer, both in primary and metastatic settings has just been published as part of a special edition on ‘Revisiting Seed and Soil: A New Approach to Target Hibernating Dormant Tumor Cells‘ in Frontiers in Oncology: Molecular and Cellular Oncology.

Extracellular Matrix in Lung Cancer
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Publication: Stromal cell diversity associated with immune evasion in human triple‐negative breast cancer

Thomas R. Cox, Aug 2020

Stromal cell diversity associated with immune evasion in human triple‐negative breast cancer

We are excited to have been part of a recent piece of work using single cell genomics to map the different cell types present with triple negative breast cancer which has recently been published in EMBO.

The work, led by Alex Swarbrick and his team here at the Garvan uncovered four new subtypes of cells within triple negative breast cancer, which contain promising new therapeutic targets for the aggressive disease. These cells produces molecules that suppress immune cells, which may help cancer cells evade the body’s immune system, and the work could lead to a new class of therapies for triple negative breast cancer.

Breast cancer stromal cell diversity
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Publication: Plasma polymerized nanoparticles effectively deliver dual siRNA and drug therapy in vivo

Thomas R. Cox, Jul 2020

Plasma polymerized nanoparticles effectively deliver dual siRNA and drug therapy in vivo

We are delighted to have been part of an exciting study looking into the potential of a new class of multifunctional nanocarrier to deliver dual siRNA and drug therapy to breast tumours which was recently published in Scientific Reports.

The work was led by our collaborators Miguel Santos and Steven Wise from the Applied Materials Group at the University of Sydney who pioneered the development of these novel multifunctional nanocarriers.

Plasma polymerized nanoparticles for cancer treatment
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Award: M&M team awarded MBSANZ paper(s) of the year

Thomas R. Cox, Feb 2020

MBSANZ

The Matrix Biology Society of Australia and New Zealand (MBSANZ) has just announced their “Paper of the Year” awards in the Early Career Research (ECR) and Mid Career Researcher (MCR) categories.

We are delighted that two papers from the Matrix & Metastasis lab and collaborators have been chosen for these awards

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Publication: Cancer Metastasis: The Role of the Extracellular Matrix and the Heparan Sulfate Proteoglycan Perlecan

Thomas R. Cox, Jan 2020

Cancer Metastasis: The Role of the Extracellular Matrix and the Heparan Sulfate Proteoglycan Perlecan

Our recent review paper in collaboration with colleagues in Sydney and Melbourne on the role of the ECM and in particular the Heparan Sulphate Proteoglycan, Perlecan, in cancer and cancer metastasis, has just been published in Frontiers in Oncology.

Perlecan (HSPG2) in Cancer

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Publication: Targeting the lysyl oxidases in tumour desmoplasia

Thomas R. Cox, Nov 2019

Targeting the lysyl oxidases in tumour desmoplasia

Our recent review discussing the importance, and also the therapeutic potential of inhibiting the lysyl oxidase (LOX) family of enzymes as a stromal targeting therapy has just been published in Biochemical Society Transactions.

The Lysyl Oxidase (LOX) Family

The Lysyl Oxidase (LOX) family of enzymes

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Publication: CAF Subpopulations: A New Reservoir of Stromal Targets in Pancreatic Cancer

Thomas R. Cox, Oct 2019

CAF Subpopulations: A New Reservoir of Stromal Targets in Pancreatic Cancer

Working together with A/Prof Paul Timpson’s lab, we are pleased to announce that our recent review on targetting CAFs in pancreatic cancer has just been published in Trends In Cancer.

In this work we explore how different aspects of CAF heterogeneity are defined and how these manifest in multiple cancers, with a focus on pancreatic ductal adenocarcinoma (PDAC).

Mechanisms of CAF Heterogeneity

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Publication: CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan

Thomas R. Cox, Aug 2019

CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan

We are super excited to announce that our recent work in close collaboration with A/Prof Paul Timpson has just been published in Nature Communications (view the full Open-Access article here)

In this work (which was a large international collaboration), co-led by our team and Paul Timpson’s team (also at the Garvan Institute), we show that remodeling of the stromal  tissue in and around pancreatic tumours may be the key to stopping their spread and improving chemotherapy outcomes.

Cancer cell CAF crosstalk

What we did

We already know that tumours are made up of heterogenous populations of cancer cells with different mutational landscapes. Furthermore, recently, the field has begun to realise that the cancer associated fibroblasts (CAFs) present in and around the tumour are also a diverse collection of  subpopulations.

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Publication: The Mini‐Organo: A rapid high‐throughput 3D coculture organotypic assay for oncology screening and drug development

Thomas R. Cox, Aug 2019

The Mini‐Organo: A rapid high‐throughput 3D coculture organotypic assay for oncology screening and drug development

Just published in Cancer Reports is our new protocol paper detailing the development of a rapid high-throughput (96wp) 3D organotypic coculture assay that is optimised for screening cancer cell and cancer-associated fibroblast response to drugs in physiologically relevant matrices.

Mini-Organo workflow

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Publication: LOXL1 Is Regulated by Integrin α11 and Promotes Non-Small Cell Lung Cancer Tumorigenicity

Thomas R. Cox, May 2019

LOXL1 Is Regulated by Integrin α11 and Promotes Non-Small Cell Lung Cancer Tumorigenicity

Our lab has contributed to a recent paper by Zeltz and colleagues looking at the interplay between Lysyl Oxidase Like 1 (LOXL1) and Integrin α11 in Non-Small Cell Lung Cancer (NSCLC). The work was published in the Open-Access journal Cancers.

LOXL1, integrin a11 and ECM crosstalk

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Publication: Proteomic Profiling of Human Prostate Cancer-associated Fibroblasts (CAF) Reveals LOXL2-dependent Regulation of the Tumor Microenvironment

Thomas R. Cox, May 2019

Proteomic Profiling of Human Prostate Cancer-associated Fibroblasts (CAF) Reveals LOXL2-dependent Regulation of the Tumor Microenvironment

A new paper has just been published revealing the role of Lysyl Oxidase Like 2 (LOXL2) in the remodelling of the prostate cancer microenvironment. The work, carried out in collaboration with lead researchers from the Cancer Program, Biomedicine Discovery Institute at Monash University has just been published in Molecular and Cellular Proteomics.

Normal Prostate Fibroblast and Cancer Associated Fibroblast proteomics

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Publication: Targeting promiscuous heterodimerization overcomes innate resistance to ERBB2 dimerization inhibitors in breast cancer

Thomas R. Cox, Mar 2019

Targeting promiscuous heterodimerization overcomes innate resistance to ERBB2 dimerization inhibitors in breast cancer

We have just published a new paper in Breast Cancer Research in collaboration with lead researcher Dr. David Croucher from the Garvan Institute, looking at how and why ERBB2 (HER2) positive breast cancer cells develop resistance to targeted therapies such as trastuzumab (Herceptin™).

Promiscuity of the ERBB2 receptor in breast cancer

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