Search anything and hit enter
  • Teams
  • Members
  • Projects
  • Events
  • Calls
  • Jobs
  • publications
  • Software
  • Tools
  • Network
  • Equipment

A little guide for advanced search:

  • Tip 1. You can use quotes "" to search for an exact expression.
    Example: "cell division"
  • Tip 2. You can use + symbol to restrict results containing all words.
    Example: +cell +stem
  • Tip 3. You can use + and - symbols to force inclusion or exclusion of specific words.
    Example: +cell -stem
e.g. searching for members in projects tagged cancer
Search for
Count
IN
OUT
Content 1
  • member
  • team
  • department
  • center
  • program_project
  • nrc
  • whocc
  • project
  • software
  • tool
  • patent
  • Administrative Staff
  • Assistant Professor
  • Associate Professor
  • Clinical Research Assistant
  • Full Professor
  • Graduate Student
  • Lab assistant
  • Non-permanent Researcher
  • Permanent Researcher
  • Pharmacist
  • PhD Student
  • Physician
  • Post-doc
  • Project Manager
  • Research Associate
  • Research Engineer
  • Retired scientist
  • Technician
  • Undergraduate Student
  • Veterinary
  • Visiting Scientist
  • Deputy Director of Center
  • Deputy Director of Department
  • Deputy Director of National Reference Center
  • Deputy Head of Facility
  • Director of Center
  • Director of Department
  • Director of Institute
  • Director of National Reference Center
  • Group Leader
  • Head of Facility
  • Head of Operations
  • Head of Structure
  • Honorary President of the Departement
  • Labex Coordinator
Content 2
  • member
  • team
  • department
  • center
  • program_project
  • nrc
  • whocc
  • project
  • software
  • tool
  • patent
  • Administrative Staff
  • Assistant Professor
  • Associate Professor
  • Clinical Research Assistant
  • Full Professor
  • Graduate Student
  • Lab assistant
  • Non-permanent Researcher
  • Permanent Researcher
  • Pharmacist
  • PhD Student
  • Physician
  • Post-doc
  • Project Manager
  • Research Associate
  • Research Engineer
  • Retired scientist
  • Technician
  • Undergraduate Student
  • Veterinary
  • Visiting Scientist
  • Deputy Director of Center
  • Deputy Director of Department
  • Deputy Director of National Reference Center
  • Deputy Head of Facility
  • Director of Center
  • Director of Department
  • Director of Institute
  • Director of National Reference Center
  • Group Leader
  • Head of Facility
  • Head of Operations
  • Head of Structure
  • Honorary President of the Departement
  • Labex Coordinator
Search
Go back
Scroll to top
Share
© Research
Event

[Seminar C3BI]-Integrated and spatial-temporal multiscale modeling of liver guide in vivo experiments in healthy & chronic disease states: a blue print for systems medicine? -by Dirk DRASDO

Scientific Fields
Diseases
Organisms
Applications
Technique
Date
20
Sep 2018
Time
14:00:00
25 Rue du Dr Roux, Paris, France
Address
Building: Lwoff Room: Retrovirus
Location
2018-09-20 14:00:00 2018-09-20 15:00:00 Europe/Paris [Seminar C3BI]-Integrated and spatial-temporal multiscale modeling of liver guide in vivo experiments in healthy & chronic disease states: a blue print for systems medicine? -by Dirk DRASDO Background and Aims:  Hyperammonemia after drug-induced peri-central liver lobule damage, as from overdosing acetaminophen (paracetamol), and can lead to encephalopathy and dead of the patient. Guided by mathematical models, the consensus set of chemical […] 25 Rue du Dr Roux, Paris, France Christophe Becavin christophe.becavin@pasteur.fr

Speakers

Dirk Drasdo
(INRIA Paris & Sorbonne Universités UPMC Univ Paris 6)

About

Background and Aims:  Hyperammonemia after drug-induced peri-central liver lobule damage, as from overdosing acetaminophen (paracetamol), and can lead to encephalopathy and dead of the patient. Guided by mathematical models, the consensus set of chemical reactions for detoxification of liver from ammonia has recently been shown to fail in explaining ammonia-detoxification after drug-induced peri-central damage (Schliess et. al., 2014). Our aim is to demonstrate how integrated and spatial-temporal models mimicking detoxification of the blood from ammonia in virtual tissue samples can assist in guiding identification of missing molecular mechanisms, or predicting the impact of micro-architectural alterations due to acute or chronic damage on ammonia detoxification. Our modeling methodology is very general.

Method:The consensus and alternative detoxification mechanisms have been implemented within mathematical integrated and spatial-temporal multi-scale models to test various hypotheses on potentially missing mechanisms in ammonia detoxification during liver regeneration after drug-induced pericentral damage in silicoin a virtual liver lobule (Drasdo et. al., J. Hepat. 2014).

The multi-scale model simulates blood flow and molecular transport in the spatial lobule micro-architecture and displays each individual hepatocyte in space and time. Detoxification reactions are executed in each virtual hepatocyte. This makes in silicotesting of hypothesized mechanisms feasible from the molecular up to the tissue scale. The results are directly compared to experiments in mouse. Finally, fibrotic streets have been added to the model to predict the possible impact of architectural distortions and micro-shunts.

Results:We demonstrate how multiscale and multilevel models guided experiments towards identification of a previously unrecognized ammonia detoxification mechanism, that has the potential of improving treatment in hyperammonemia (Ghallab et. al., J. Hepat. 2016). The same model predicts for CCl4-induced fibrosis a reduced detoxification capacity for ammonia. Finally we outline how the whole body scale can be included to arrive at a model spanning molecular up to whole body scale permitting to study the relation of molecular changes and micro-architecture on whole body blood circulation, and briefly summarize results of integration of APAP toxic pathway as HGF signaling.

Conclusion:Refined multi-scale models increasingly permit realistic prediction of liver function as well as of toxic injury in acute and chronic damage states. Those models can integrate data from various sources, in vitro, different animal models or human data. The direct representation of liver micro-architecture in those models will open up the future perspective to feed these models with patient-specific data, hence generating a virtual twin of a patients’ liver to guide personalized diagnosis and therapy planning.

Location

Building: Lwoff
Room: Retrovirus
Address: 25 Rue du Dr Roux, Paris, France