Ursula Klingmüller

C-TIP-HCC- Mechanism-based Multiscale Model to Dissect the Tipping Point from Liver Cirrhosis to Hepatocellular Carcinoma

The ultimate goal of the C-TIP-HCC is a „mechanistic multiscale model to describe dynamic changes in regenerative nodes across a tipping point (TIP) towards development in patients with cirrhosis to facilitate early monitoring and intervention“ and facilitate intervention“. To achieve this, we will conduct in-depth studies on cirrhotic regenerative nodes.

Forschungsnetzwerk zur Früherkennung und Prävention- LiSyM-Krebs

Ein Netzwerk von Klinikern, Wissenschaftlern und Datenmanagern hat sich zur Aufgabe gemacht, Methoden zu entwickeln, um Patienten mit einem hohen Risiko für ein Leberkarzinom frühzeitig, in Vorstadien der Tumorentwicklung, identifizieren zu können. Gemeinsam bilden sie das „Systemmedizinische Forschungsnetzwerk zur Früherkennung und Prävention von Leberkrebs“, LiSym-Krebs, das vom Bundesministerium für Bildung und Forschung ...

SMART-NAFLD : A Systems Medicine Approach to Early Detection and Prevention of Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease

The massive increase in obesity is leading to an alarming rise in non-alcoholic liver disease (NAFLD). This development will lead to a dramatic increase in liver diseases such as hepatocellular carcinoma (HCC). A particular challenge is that NAFLD-associated HCCs, for reasons still unknown, not only occur in association with advanced liver fibrosis/cirrhosis, ...

This generic project is intended to be a forum for all LiSyM partner and external stakeholders interested in participating in the BMBF initiative LiSyM-Krebs.

This comprises the whole LiSyM network

Upon stimulation of cells with transforming growth factorb(TGF-b),Smad proteins form trimeric complexes and activate a broad spectrum of target genes. It remains unresolved which of the possible Smad complexes are formed in cellular contexts and how these contribute to gene expression. Combining quantitative mass spectrometry with a computational selection strategy, we investigate Smad complexes in the mouse hepatoma cell line Hepa1-6.

In this study, we characterize Western diet-induced phenotypic changes in murine 392 hepatocytes and employ dynamic pathway modelling to resolve the underlying molecular 393 mechanisms resulting in altered intracellular signal transduction and enhanced proliferation 394 of WD hepatocytes.

Primary hepatocytes from a preclinical mouse model fed with high-sugar and high-fat diet are used to develop a data-based mathematical model that identifies the basal phosphorylation rate of the tyrosine kinase receptor MET as the main dysregulated parameter driving fatty liver disease.

Image for https://doi.org/10.1038/s44320-023-00007-4

ODE model describes dynamics of IFNalpha-induced signaling in Huh7.5 cells for a time scale up to 32 hours after stimulation with IFNalpha. The model consists of an IFN receptor model, formation/degradation and cytoplasmic/nuclear shuttling of STAT1-homodimers, STAT1-STAT2-heterodimers and STAT1-STAT2-IRF9 (ISGF3) complexes. On top, formation of feedback proteins STAT1, STAT2, IRF9, USP18, SOCS1, SOCS3 and IRF2 and corresponding influences on IFNalpha signaling dynamics was incorporated. The model ...

Isolation of primary mouse hepatocytes

Jamboree presentation

Workshop #1 LiSym status seminar March 2023, Dresden “Towards concordant multiomics of liver”

Agenda for LiSyM-Cancer status seminar 2022

Agenda Kickoff Meeting SMART-NAFLD 1-2 december 2021 in Heidelberg