Liver

Research Networks

Early Detection and Prevention of Liver Cancer

Systems medicine research network for the early detection and prevention of liver cancer

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LiSyM-Cancer Mission

Liver Systems Medicine Cancer – LiSyM-Cancer – is a multidisciplinary research network funded by the Federal Ministry of Education and Research (German: Bundesministerium für Bildung und Forschung, BMBF) within the Framework of the National Decade Against Cancer. The funding period is July 2021 until July 2024.

More info on the funding program: "Funding of a Systems Medicine Research Network for the Early Detection and Prevention of Liver Cancer".

The LiSyM-Cancer research network builds on the achievements of the previous network LiSyM (funding period 2016 to 2021) and is extending the research focus to liver cancer.

In the LiSyM-Cancer network, molecular and cell biologists, clinical researchers and experts in mathematical modeling are jointly conducting research to investigate the development of liver cancer from pre-existing conditions such as non-alcoholic fatty liver or liver cirrhosis. The aim of the joint project is to identify relevant biomarkers to diagnose and prevent hepatocellular carcinoma (HCC) at early stages.

LiSyM-Cancer furthermore addresses the following questions:

  1. What are the similarities and differences of the HCCs arising in patients with fatty liver disease in the absence of cirrhosis versus those that develop in patients with liver cirrhosis?
  2. Which factors or mechanisms explain that men are significantly more likely to develop liver cancer than women?
  3. Which components in the blood reflect a crossing of the tipping points for liver cancer development and could be used as biomarkers for early detection?
  4. Which parameters of tipping point exceedance could serve as target structures that prevent or significantly delay the development of HCC?

Integrative Systems Medicine Approach

LiSyM-Cancer comprises three projects:

  • SMART-NAFLD,
  • C-TIP-HCC,
  • DEEP-HCC, and the
  • Programme and Data Management

The project partners use an integrative systems medicine approach in which liver cell communication, metabolism and signal transduction as well as the dynamics of the different liver cell populations and the composition of the extracellular matrix are examined.

High-standard multi- and spatial-OMICS and imaging methods are applied. Based on quantitative data, mathematicians and bioinformaticians develop models to enable the early detection of alterations (tipping points) facilitating liver cancer development.

Although most liver cancers develop based on cirrhosis (tipping point 2), due to the rapid increase of overweight and obese patients with NAFLD, the first tipping point is becoming increasingly important.

SMART-NAFLD C-TIP-HCC DEEP-HCC Steatohepatitis Tipping point 1 HCC Cirrhosis Tipping point 2 HCC Time Cancer Development

The three consortia in LiSyM-Cancer:

  • SMART-NAFLD characterises the transition from NAFLD directly to HCC (tipping point 1)
  • C-TIP-HCC investigates the transition from liver cirrhosis to HCC (tipping point 2)
  • DEEP-HCC provides an multi-dimensional characterisation of early HCC.

LiSyM-Cancer Projects

SMART-NAFLD

SMART-NAFLD focuses on alterations in metabolism and signal transduction that favor disease progression to liver cancer. The project aims to identify alarm signatures in the blood of patients with fatty liver diseases without cirrhosis. This will facilitate to develop model-based trajectories for individual patients to evaluate the closeness to the tipping point towards liver cancer (tipping point 1).

Illu SMART-NAFLD

C-TIP-HCC

C-TIP-HCC employs multiscale modeling to address structural and compositional changes in the extracellular matrix, and differences in cellular phenotypes in cirrhotic nodules. This facilitates the discrimination of the tissue in compensated cirrhosis across a tipping point towards liver cancer formation (tipping point 2). Aim of the modeling is to predict strategies to prevent or slow down disease progression from cirrhosis to liver cancer.

Illu C-TIP-HCC

DEEP-HCC

DEEP-HCC focuses on early liver cancer and provides an unprecedented deep multi-dimensional functional and spatial characterization, with tissue-to-single cell precision. A comprehensive data set will be generated consisting of 3D digital tissue reconstruction, spatial transcriptomics, epigenetics, lipidomics, pseudotime-ordered somatic mutations and personalized complex liver cancer organoids. This unique convergence of datasets will be integrated within a comprehensive metabolic/signaling-, spatio-temporal- and stochastic modelling workflow, to reveal emergent multimodal liver cancer signatures.

Illu DEEP-HCC

DMPM

The essential goal of the Program Directorate and Management is to enable and support network collaborations across the projects. Synergies between the consortia are mediated to ensure achievement of the working plans. The Project and Communications Management Team works closely with the Program Director, SAB, and Network Coordinators to facilitate the successful implementation of the program and the publication and usability of the results. The data management team ensures the flow of data, data exchange and data backup within the consortia and across the network according to the FAIR criteria.

Illu DMPM

News & Events

Date

Start of second funding period LiSyM-Cancer

As of July 1st 2024 the second funding period of the research network LiSyM-Cancer started.

Start of second funding period LiSyM-Cancer
Date

Stay abroad Sophia MĂĽller-Dott

The computational biologist Sophia MĂĽller-Dott spent three months at the University of Copenhagen as part of her doctoral thesis in the LiSyM-Cancer research network (group of Julio Saez-Rodriguez). She worked on two projects at the Center for Protein Research in Jesper V. Olsen's group and very much appreciated the close contact with the experimentalists, as she reports in the interview.

Stay abroad Sophia MĂĽller-Dott
Location
Leipzig
Date

LiSyM-Cancer Status Seminar 2024

The last Status Seminar of the current funding period brought together 69 participants from C-TIP-HCC, DEEP-HCC, SMART-NAFLD and Program and Data Management in the beautiful Salles de Pologne in Leipzig.

LiSyM-Cancer Status Seminar 2024
Location
Leipzig, Germany
Date

Interaction and scientific discussions at SBMC 2024 in Leipzig

At the SBMC 2024 in Leipzig participants discussed and exchanged cutting-edge research in systems biology. The conference, hosted at Leipzig University's Paulinum, featured keynote talks, poster sessions, and panel discussions, highlighting interdisciplinary research and future clinical applications.12

Interaction and scientific discussions at SBMC 2024 in Leipzig
Location
Leipzig, Germany
Date

SBMC 2024

9th Conference on Systems Biology of Mammalian Cells – Translating Systems Medicine into the Clinics

SBMC 2024
Date

SMART-NAFLD On YouTube

„Do you have that disease? We are talking about Fatty liver.” Doktor Whatson – well-known German YouTube Influencer – talks to Ursula Klingmüller and her SMART-NAFLD group their liver cancer research.

SMART-NAFLD On YouTube
Date

Liver Cancer Awareness Month

October is Liver Cancer Awareness Month. More than 800,000 people died from liver cancer in 2020, making liver cancer the third most common cause of cancer death globally.

Liver Cancer Awareness Month
Location
Bad Staffelstein, Germany
Date

LiSyM-Cancer Scientist Retreat

What’s behind Tipping points, Crosstalk, Barriers, and Digital twins?

LiSyM-Cancer Scientist Retreat