Michael Kücken

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 ...

DEEP-HCC - Detailed Analysis of the Spatial Organization of the Development of Hepatocellular Carcinoma

This comprises the whole LiSyM network

One of the tasks of the healthy liver is to store fat. Yet, at some stage, too much fat makes the liver sick. One critical time point occurs when a healthy fatty liver becomes inflamed and progresses to steatohepatitis, or NASH. LiSyM-Pillar I will identify what events lead to this transition. Does it occur in all parts of the liver? Which molecules indicate that it is taking place? Can the degeneration be stopped or undone - and if so, how?

Experimental assay Human-NAFLD/HO , 4 biopsies from healthy obese patients. Samples for the HO category were obtained in patients undergoing bariatric surgery with a BMI > 30 and subgroups defined by liver histology as follows: HO samples showed a normal liver histology such as the NC samples.

-h692a -h6758 -h6922 -h7230

All file here

Files can be opened and visualised with http://motiontracking.mpi-cbg.de/get/ software

Experimental assay Human-NAFLD/NC 6 biopsies from normal control patients. : NC samples showed steatosis ≤5%, no inflammation, no ballooning and no fibrosis and were obtained during liver resections or biopsy in non-hepatobiliary malignancy in patients with a BMI<30kg/m2. Livers were either free of metastases or a distance of at least 2 cm to the next metastasis observed.

Image data for this assay available via link to file folder containing ...

The model studies the influence of hepatocyte–sinusoid alignment (HSA), i.e. the orientation of the division plane such that daughter hepatocytes align with nearby sinusoids, on the shape of tumor nodules in liver lobules. It employs the structure of the model ‘Liver Regeneration from CCl4’ (https://seek.lisym.org/models/19).

Originally, Höhme et al. (https://doi.org/10.1007/s11538-017-0375-1) employed a center-based model. Here, the model is encoded in the standardized language MorpheusML. ...

In the experimental paradigm of CCl4 intoxication of mice, hepatocytes around the central vein (located in the center of an idealized hexagonal liver lobule) are dying and are subsequently replaced by new hepatocytes, largely through activation of proliferation in the remaining hepatocytes.

Alignment of daughter hepatocytes along the orientation of the closest sinusoid, a process which is named hepatocyte-sinusoid alignment (HSA), was proposed by Höhme et al. (https://doi.org/10.1073/pnas.0909374107) ...

Model for the interaction of Wnt and Hh as published in Kolbe et al.: Mutual Zonated Interactions of Wnt and Hh Signaling Are Orchestrating the Metabolism of the Adult Liver in Mice and Human, Cell Reports, 29,4553,

https://doi.org/10.1016/j.celrep.2019.11.104

Code for the bile flow model in Segovia-Miranda et al.: Three-dimensional spatially resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression (https://www.nature.com/articles/s41591-019-0660-7)

See the README file in the link for details installing and running the code.

Computational modeling and simulation become increasingly important for Systems Medicine. A number of corresponding software tools have been developed but require scientists to encode their models in an imperative programming language. Morpheus [1,2], on the other hand, is an extensible open-source software framework that is entirely based on declarative modeling. It uses the domain-specific language MorpheusML to define multicellular models through a user-friendly GUI and has since proven ...