Systems Oncology

Stiffness in Pancreatic Cancer

Reducing the stiffness of the PDAC organoid environment results in cells creating ductal-like structures as they develop from original more firm area into the softer area.

PDAC organoids SO1 from Systems Oncology

Scientific breakthrough

How cancer cells control healthy cells

Breakthrough study sheds light on how cancer cells and normal cells communicate with each other, opening up new approaches to cancer treatment.
Researchers found faulty versions of the KRAS gene – the most commonly mutated gene in cancer – have an important effect on healthy tissue. Mutated KRAS becomes hyperactive and helps drive cancer cells’ rapid and uncontrolled growth. They show mutated KRAS also plays an important role in turning healthy ‘stromal cells’ into cancer’s allies.
A communication loop with a cancer-causing gene controlling cancer via healthy stromal cells was identified in cells from pancreatic ductal adenocarcinoma – one of the deadliest forms of cancer.
Cancer cells use mutant KRAS to coerce neighbouring healthy tissue into helping with the disease’s growth and spread.

We now know that tumours are a complex mix of genetically diverse cancer cells and multiple types of healthy cells, all communicating with each other via an intricate web of interactions. Untangling this web, and decoding individual signals, is vital to identify which of the multitude of communications are most important for controlling tumour growth and spread. We have identified a key role played by the most commonly mutated gene in cancer in communicating with healthy cells. Blocking its effects could be an effective cancer treatment.

Claus Jorgensen

Senior Group Leader

A note from group leader – Claus Jørgensen

My research interest is mainly focused on systems-level analysis of signalling networks in cellular decision processes and how these are deregulated in cancer. I am particularly interested in understanding how aberrations in cellular signalling networks promote tumorigenesis and how the tumour microenvironment affects tumour cell signalling and malignant progression.   

In my laboratory we focus on identifying and delineating the regulatory mechanisms whereby tumour cells co-opt stromal cells and how the ‘activated’ stromal cells affect tumour cell behaviour (malignant progression, drug sensitivity and metastasis). To establish the specificities of signalling networks and how they impinge on specific cellular processes, we use Mass Cytometry (CyTOF), CRISPR editing/screening, sequencing and quantitative mass spectrometry to systematically measure signalling on a global level. Through data-integrative approaches, we aim to describe how signals are processed in a cell-specific manner. The long-term goals are to understand how specific signals are processed to promote tumour progression and how blocking these signals can enhance therapeutic response. 

Meet the Systems Oncology Team

It’s a great pleasure to introduce the Systems Oncology group, who are a joy to work with as they are always eager to support each other and welcome new members to the teamThey are dedicated to improving outcomes for cancer patients through working collaboratively on innovative research – and having fun at the same time.  

Claus Jørgensen Deputy Director & Senior Group Leader
Claus Jørgensen

Deputy Director & Senior Group Leader

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Soren Buchholz

Sponsored Researcher

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Luisa Ferreira

Postdoctoral Fellow

Nasir Haider Associate Scientist
Nasir Haider

Associate Scientist

Seung Hyun Lee Clinical Fellow
Seung Hyun Lee

Clinical Fellow

Joanna Kelly Senior Scientific Officer
Joanna Kelly

Senior Scientific Officer

Sofia Kochkina
Sofia Kochkina

PhD Student

Ramya Purkanti Principal Computational Biologist
Ramya Purkanti

Principal Computational Biologist

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Carol McMenemy

Postdoctoral Fellow

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Carmen Rodriguez-Cupello

Postdoctoral Fellow

Louis Roussel Phd Student
Louis Roussel

Phd Student

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Luke Taylor

Translational Research Facilitator

Yihan Xu PhD Student
Yihan Xu

PhD Student

Xiaohong Zhang Senior Scientific Officer
Xiaohong Zhang

Senior Scientific Officer

Microscopic image of pancreatic tissue, showcasing cellular structures and morphology
Microscopic image of a PEG implant at 18x magnification, highlighting surface features and structural details

Research areas

Mapping the tumour microenvironment of PDA 

Due to the abundant tumour microenvironment much emphasis has been given to mapping of signalling pathways by which tumour cells conscript host cells. Pre-clinical studies have further demonstrated that these pathways can be successfully targeted to improve therapeutic response. However, in some cases, therapeutic and genetic targeting of the microenvironment has resulted in accelerated disease progression rather than retardation.

Modelling human pancreatic cancer

Tumour cells are embedded in a biophysically stiff environment and constitute less than 15% of the tumour volume in patients, yet most in vitro models do not replicate these aspects. In an ongoing collaboration with Prof Linda Griffith (MIT) and Prof Martin Humphries (UoM) we have adapted a fully synthetic scaffold to support the growth of both tumour and host cells.

Tumour stromal interactions control tumour growth and metastasis

Tumour cells co-opt stromal cells to secrete signals, which in turn expand the signalling network tumour cells can engage. Due to the complexity of the tumour microenvironment, we interrogated how stromal reciprocal signals depend on the stromal cellular composition.

Mapping the tumour microenvironment of PDA 
Modelling human pancreatic cancer
Tumour stromal interactions control tumour growth and metastasis

Some of our research images

Systems oncology research visualization with molecular and cellular details
Pancreatic cancer organoids co-cultured with fibroblasts
Pancreatic-organoids-3D
Pancreatic ductal adenocarcinoma
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FAQS

While we are not involved in treating patients, we collaborate with clinicians and the MCRC Biobank to use patient samples in our workWe create 3D tumour models based on patient tissue grown in the laboratory, making these models highly relevant tools to study the growth of pancreatic cancer, the signals sent between cancer and host cells, and for investigating new treatment options.  

We work with research partners across the University of Manchester, around the UK and internationallyGet in touch with us using the contact form, we’re always open to new ideas and collaborations. 

We are currently advertising for a PhD student, please see the student pages [link] for full detailsAnd if you are interested in our work, please feel free to get in touch directly using the contact form at any time.

All publications

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https://doi.org/10.1186/s12943-024-02157-x

The PI3K-AKT-mTOR axis persists as a therapeutic dependency in KRASG12D-driven non-small cell lung cancer

12 November 2024

Institute Authors (1)

Amaya Viros

Labs & Facilities

Genome Editing and Mouse Models

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Research Group

Skin Cancer & Ageing

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https://doi.org/10.1186/s13045-024-01610-0

The small inhibitor WM-1119 effectively targets KAT6A-rearranged AML, but not KMT2A-rearranged AML, despite shared KAT6 genetic dependency

8 October 2024

Institute Authors (6)

Georges Lacaud, Mathew Sheridan, Michael Lie-a-ling, Liam Clayfield, Jessica Whittle, Jingru Xu

Research Group

Stem Cell Biology

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/wp-content/uploads/2024/11/Annual-Report-2023.pdf

2023 Annual Report

13 September 2024

https://doi.org/10.1126/science.adh7954

Vitamin D regulates microbiome-dependent cancer immunity

25 April 2024

Institute Authors (1)

Evangelos Giampazolias

Research Group

Cancer Immunosurveillance

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https://doi.org/10.1038/s41684-024-01363-w

Streamlining mouse genome editing by integrating AAV repair template delivery and CRISPR-Cas electroporation

10 April 2024

Institute Authors (1)

Natalia Moncaut

Labs & Facilities

Genome Editing and Mouse Models

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https://www.biorxiv.org/content/10.1101/2023.12.13.568969v1

A novel human model to deconvolve cell-intrinsic phenotypes of genetically dysregulated pathways in lung squamous cell carcinoma

14 December 2023

Institute Authors (3)

Carlos Lopez-Garcia, Caroline Dive, Anthony Oojageer

Research Group

Translational Lung Cancer Biology

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