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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People: M&M continues to grow…

Thomas R. Cox, Jan 2019

We are looking forward to the imminent arrival of our newest member, Gretel Major who is joining the group this week.

Gretel Major (Matrix and Metastasis Lab)

Gretel is joining us a new Research Assistant (RA) in the Matrix and Metastasis team having recently completed her Bachelor of Advanced Science (Honours) degree at the University of Wollongong under the mentorship of Prof. Marie Ranson.

Gretel joins us to work on our different projects underway looking at the role of the extracellular matrix (ECM) in cancer progression, and is particularly interested in developing her translational research skills.

 

Publication: The extracellular matrix as a key regulator of intracellular signalling networks

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.

Extracellular matrix interplay with MAPK-JNK Signalling

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.

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People: M&M 2019 Honours Students

Thomas R. Cox, Jan 2019

The Matrix and Metastasis group is excited to be welcoming two new Honours students to the team for 2019.

Yordanos Setargew (left) and Shivanjali Ratnaseelan (right) will both be joining us to spend the next 10 months in the lab as part of their UNSW Sydney, School of Medical Sciences (SoMS) Honours Program.

Yordanos Setargew Shivanjali Ratnaseelan

Yordanos will be looking at new ways to target the lysyl oxidase (LOX) family in pancreatic cancer, and Shivanjali will be looking at how the biomechanical properties of the tumour microenvironment alter breast cancer cell sensitivity to chemotherapy.

News: Anti-fibrotic LOX family inhibitor program to commence Phase I trials

Thomas R Cox, Nov 2018

We’re exited to reveal that we have been working hard with Pharmaxis on the development of their lysyl oxidase (LOX) systemic inhibitor for the potential use as a stromal co-targeting agent in pancreatic cancer.

Pharmaxis has developed an oral drug that inhibits all LOX family members, and which has shown to lead to significant reductions in fibrosis (scarring) in in-vivo models of kidney fibrosis, lung fibrosis, myelofibrosis and now with our help, in models of pancreatic cancer.

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People: New starter for M&M

Thomas R. Cox, Oct 2018

We’re pleased to welcome our newest Animal Technician Michelle Yam to the team. Michelle is returning home to Australia having worked at West Virginia University in the US.Michelle Yam (Matrix and Metastasis Lab)

Michelle joins us and will take care of the welfare and maintenance of the animals used in our cancer research program to ensure we conform to the Australian Code for the Care and Use of Animals for Scientific Purposes and the New South Wales Animal Research Regulations.

Publication: Cancer cell ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential

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

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.

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People: Introducing our first PhD Student – Michael Papanicoloau

Thomas R. Cox, Sep 2018

Michael Papanicoloau - Matrix and MetastasisThe lab is excited to be welcoming our first Ph.D. student Michael Papanicoloau who has just started in the lab. Michael joins us after completing his Honours degree in Biomedical Science at UTS and the Woolcock Institute of Medical Research.

Having been awarded a prestigious UTS Research Excellence Scholarship, Michael’s Ph.D. will focus on understanding how the extracellular matrix changes over time in solid tumours, in particular breast cancer, and how these changes feed into the pathological progression of the disease at both primary and secondary sites.

 

Publication: Tumor endothelial marker 8 promotes cancer progression and metastasis

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.

Tumor endothelial marker 8 promotes cancer progression and metastasis

Proposed mechanism behind the impact of TEM8 on breast and CRC cancer progression.

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