Author Archives: Matrix and Metastasis

About Matrix and Metastasis

Matrix & Metastasis Lab | Targetting the Extracellular Matrix in Cancer

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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News: Launch of the Australian Pancreatic Cancer Matrix Atlas (APMA)

Thomas R. Cox, Jun 2020

Australian Pancreatic Cancer Matrix Atlas (APMA) as a national and international portal for pancreatic cancer and matrix biology research

We are delighted to announce the launch of our Avner Australian Pancreatic Cancer Matrix Atlas (APMA) as a national and international portal for pancreatic cancer and matrix biology research.

About APMA

Desmoplasia (fibrosis) is a key hallmark of pancreatic cancer, which can be targeted in concert with tumour cell-centric therapies. The overarching goal of APMA is to facilitate the translation of stromal-centric therapy as a mainstay in our emerging multimodal armoury against pancreatic cancer.

APMA is a collaborative effort by researchers at the Garvan Institute of Medical Research and The Kinghorn Cancer Centre in Sydney, working closely with clinical teams at Royal North Shore Hospital.

Committee Members

Prof. Paul Timpson, A/Prof. Thomas Cox, A/Prof. Marina Pajic, Prof. Anthony Gill, Dr. Brooke Pereira, Dr. David Herrmann, Prof. Jas Samra, Amber Johns, Gloria Jeong.

Vision and goals

APMA’s aim is to better understand how the dynamic extracellular matrix landscape is linked to alterations in drug response and patient survival in pancreatic cancer. By mapping the histological, immunohistochemical, and proteomic differences between normal pancreatic tissue and matched pancreatic cancer samples we aim to define which matrix elements are deregulated in this disease and reveal new targets.

Detailed comprehensive mapping of the topology and 3D structure of the matrix in native pancreatic tissue and pancreatic cancer, in correlation with clinicopathological and genetic sequencing data, has not been possible until now. The Garvan Institute of Medical Research, working with the Royal North Shore Hospital (RNSH) here in Australia are perfectly placed to achieve this, thereby establishing the first national and international comprehensive human pancreatic cancer matrix database.

APMA is positioned to become an international resource held in Australia for pancreatic cancer matrix targeting, creating a portal for matrix biology researchers and clinicians to interrogate and query disease progression, outcome, survival and relapse in the context of matrix composition and 3D matrix topology. APMA integrates our laboratory based studies of the matrix with clinicopathological data including survival, relapse, and resistance, to identify matrix companion biomarkers and actionable targets that may be diagnostic and/or prognostic.

Contact and further information

Avner Australian Pancreatic Cancer Matrix Atlas (APMA)
https://www.pancreaticcancer.net.au/apma/
APMA@garvan.org.au

Funding

This project was made possible by an Avner Pancreatic Cancer Foundation Grant.

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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People: Farewell and good luck…

Thomas R. Cox, January 2020

As with any new lab (M&M turned 3 a couple of months ago 🎉), the first few years are typically about building a reliable team to help a new PI lay the foundations for establishing a functioning (and hopefully successful) research laboratory. The actual hiring process is incredibly stressful for new PI’s, often agonising for days over their first few hires. A bad hire when starting out can really set you back when the lab is in a fledgling state. At the same time, the inevitable moving on of good hires can be equally as hard…

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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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People: Our newest M&M starter – Kaitlin

Thomas R. Cox, Jan 2020

We are pleased to announce that Kaitlin Wyllie has just joined the Matrix & Metastasis team as a Research Assistant.
Kaitlin Wyllie - Matrix & Metastasis

Kaitlin recently completed her Master of Research (M.Res.) at the Department of Molecular Sciences at Macquarie University.

Kaitlin will join our projects looking at the role of the ECM in breast cancer therapy and our efforts to develop novel targeting approaches.

 

People: First Class Honours all round…

Thomas R. Cox, Dec 2019

I am delighted to share the news that our two wonderful Honours Students for 2019, Yordanos Setargew and Shivanjali Ratnaseelan have both been awarded First Class Honours from the School of Medical Sciences at UNSW Sydney. Yordanos for her project on “Targeting lysyl oxidase driven fibrosis in pancreatic ductal adenocarcinoma via copper inhibition” and Shivanjali for her project on the “Role of Extracellular Matrix Stiffness on Tumor Cell Response to Therapy”

Congratulations to both 🙂

 

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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Award: St Vincent’s Clinic Foundation Award to Elysse

Thomas R. Cox, Nov 2019

I’m delighted to announce that Elysse from the Matrix and Metastasis Team has just been awarded the St Vincent’s Clinic Foundation K&A Collins Cancer Research Award.

Elysse_SVCF_AwardThe St Vincent’s Clinic Foundation was established in 1992 to further the educational and research objectives of St Vincent’s Clinic and the surrounding precinct. The Foundation provides much-needed seed funding towards real research projects for real people including medical, basic and multidisciplinary research. The Awards are given to support bright young researchers who can put their research into real-world practise to improve patient care and health outcomes for the community.

The award which was announced at the annual Sandra David Oration, will give Elysse the opportunity (and $50,000 of seed funding) to further her novel work to find new and effective treatments for breast cancer to improve the clinical care and outcomes for patients.

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