Thomas R. Cox, Feb 2020
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
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.
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 of enzymes
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).
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.
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.
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.
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.
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.
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™).
Thomas R. Cox, Jan 2019
The extracellular matrix as a key regulator of intracellular signalling networks
Our latest review in collaboration with Dr. David Croucher and Dr. Dirk Fey on ‘The extracellular matrix as a key regulator of intracellular signalling networks‘ has just been published as part of a special series on ‘Translating the Matrix’ in the British Journal of Pharmacology.
Computational model of the interplay between the ECM and drug activated MAPK‐JNK signalling network.
At their simplest, cells follow a set of rules governed by their genetic code. These rules, which are executed by the protein‐based signalling networks that the genes encode, control the assimilation of information and decision‐making processes that shape a cell’s response to their surroundings.
Thomas R. Cox, Oct 2018
Cancer cell ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential
Just published in Molecular Biology of the Cell is our recent paper looking at the effect of extracellular matrix stiffness on the intrinsic biomechanical properties of cancer cells. Led by Professors Janine Erler (Biotech Research & Innovation Centre) and Lene Oddershede (Niels Bohr Institute) both from the University of Copenhagen, the study combines optical tweezers–based microrheology and deformability cytometry with 3D biological models to dissect how cancer cells biomechanically interact with and respond to the stiffness of the microenvironment they are within.
Optical Tweezers Schematic for measuring intracellular viscosity
The results show that invasive cancer cells adjust their intracellular and overall viscoelasticity to ECM density, and that cancer cell viscosity increases during invasion into 3D collagen matrices.
Thomas R. Cox, Sep 2018
Recent advances in understanding the complexities of metastasis
We are excited to announce that our recent F1000 Faculty Invited Review on “Recent advances in understanding the complexities of metastasis” has just been published in F1000Research.
Thomas R. Cox, Jul 2018
Tumor endothelial marker 8 promotes cancer progression and metastasis
Our new paper has just been published in Oncotarget. In this study, we show that Tumor endothelial marker 8 (TEM8) regulates the expression of multiple genes. In particular, we observed that the most common expression changes conserved between breast and colorectal cancer are involved in regulation of the cell cycle. In line with the microarray results we show that TEM8 regulates cancer cell proliferation and primary tumor growth. Since TEM8 KO tumors presented with fewer blood vessels we hypothesize that TEM8 contributes to the regulation of angiogenesis, likely by being secreted by cancer cells to alter endothelial cell migration and thereby supporting growth of the tumor. Moreover, we confirm that TEM8 is an important player in driving tumor cell invasion and metastatic dissemination in breast cancer.
Proposed mechanism behind the impact of TEM8 on breast and CRC cancer progression.
Thomas R. Cox, Jul 2018
Removing physiological motion from intravital and clinical functional imaging data
Galene is a new tool just published in eLife that can correct for physiological motion in live imaging data post-acquisition.
Understanding how molecules and cells behave in living animals can give researchers key insights into what goes wrong in diseases such as cancer, and how well potential treatments for these diseases work. Continue reading
Thomas R. Cox, Apr 2018
Charting the unexplored extracellular matrix in cancer
Our new review on the recent advances in mapping the extracellular matrix in cancer has just been published in the International Journal of Experimental Pathology.
Composed of hundreds of different building blocks, the extracellular matrix (ECM) makes up the complex, highly cross‐linked, three‐dimensional (3D) network of macromolecules (proteins, glycoproteins and its subgroup of proteoglycans, polysaccharides (glycosaminoglycans), elastins and carbohydrates) that surround cells. It is essential to correct organisation and function of all tissues and organs, yet we know remarkably little about the assembly and organisation of these supramolecular structures of the ECM. In this review we discuss some of the recent advances and technologies that are helping us delve deeper into the matrix and further our understanding of the impact that dysregulated ECM has in diseases such as cancer.
Extracellular matrix building blocks