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Dirk Drasdo

About Dirk Drasdo:
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SEEK ID: https://seek.lisym.org/people/94

Location: France

Expertise: Not specified

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Related items

Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III)

The incidence of this life-threatening acute-on-chronic liver failure (ACLF) is increasing, and early detection and cure are urgent clinical needs. Pillar III applies a Systems Medicine approach to identify the critical mechanisms of acute-on-chronic liver failure (ACLF) and to foster liver regeneration and repair.

Public web page: Not specified

Chronic Liver Disease Progression (LiSyM-DP - Pillar II)

Chronic liver diseases (CLD) progression leads to cirrhosis, often cancer, and ultimately to organ failure and death. Because of the complexity of this scenario, a Systems Medicine approach is chosen to develop strategies to better characterize progression and resolution of fibrosis. Pillar II aims to define key molecular mechanisms and structural changes in tissue architecture during the progression of CLD by visualizing and quantifying at a cellular level, tissue and organ scale.

Public web page: Not specified

LiSyM network

This comprises the whole LiSyM network

Public web page: http://www.lisym.org

LiSyM Scientific Leadership Team

Day-to-day science within the LiSyM is overseen and directed by the the LiSyM Scientific Leadership Team. This coordination team comprises the pillar coordinators and additional LiSyM members, and ensures smooth interaction between multi-skilled groups, often working in different institutions and across significant distances within Germany.

Public web page: http://www.lisym.org/governance

Influence of Liver Fibrosis on Lobular Zonation
Model Guided Pharmacotherapy In Chronic Liver Disease (LiSyM-MGP)

Abstract (Expand)

Little is known about how liver fibrosis influences lobular zonation. To address this question, we used three mouse models of liver fibrosis, repeated CCl4 administration for 2, 6 and 12 months to … induce pericentral damage, as well as bile duct ligation (21 days) and mdr2−/− mice to study periportal fibrosis. Analyses were performed by RNA-sequencing, immunostaining of zonated proteins and image analysis. RNA-sequencing demonstrated a significant enrichment of pericentral genes among genes downregulated by CCl4; vice versa, periportal genes were enriched among the upregulated genes. Immunostaining showed an almost complete loss of pericentral proteins, such as cytochrome P450 enzymes and glutamine synthetase, while periportal proteins, such as arginase 1 and CPS1 became expressed also in pericentral hepatocytes. This pattern of fibrosis-associated ‘periportalization’ was consistently observed in all three mouse models and led to complete resistance to hepatotoxic doses of acetaminophen (200 mg/kg). Characterization of the expression response identified the inflammatory pathways TGFβ, NFκB, TNFα, and transcription factors NFKb1, Stat1, Hif1a, Trp53, and Atf1 among those activated, while estrogen-associated pathways, Hnf4a and Hnf1a, were decreased. In conclusion, liver fibrosis leads to strong alterations of lobular zonation, where the pericentral region adopts periportal features. Beside adverse consequences, periportalization supports adaptation to repeated doses of hepatotoxic compounds.

Authors: Ahmed Ghallab, Maiju Myllys, Christian Holland, Ayham Zaza, Walaa Murad, Reham Hassan, Yasser A Ahmed, Tahany Abbas, Eman Abdelrahim, Annika Schneider, Madlen Matz-Soja, Joerg Reinders, Rolf Gebhardt, Theresa Hildegard Wirtz, Maximilian Hatting, Dirk Drasdo, Julio Saez-Rodriguez, Christian Trautwein, Jan Hengstler

Date Published: 1st Dec 2019

Journal: Cells

A multilevel framework to reconstruct anatomical 3D models of the hepatic vasculature in rat livers
Early Metabolic Injury (LiSyM-EMI - Pillar I)

Abstract (Expand)

The intricate (micro)vascular architecture of the liver has not yet been fully unravelled. Although current models are often idealized simplifications of the complex anatomical reality, correct … morphological information is instrumental for scientific and clinical purposes. Previously, both vascular corrosion casting (VCC) and immunohistochemistry (IHC) have been separately used to study the hepatic vasculature. Nevertheless, these techniques still face a number of challenges such as dual casting in VCC and limited imaging depths for IHC. We have optimized both techniques and combined their complementary strengths to develop a framework for multilevel reconstruction of the hepatic circulation in the rat. The VCC and micro-CT scanning protocol was improved by enabling dual casting, optimizing the contrast agent concentration, and adjusting the viscosity of the resin (PU4ii). IHC was improved with an optimized clearing technique (CUBIC) that extended the imaging depth for confocal microscopy more than five-fold. Using in-house developed software (DeLiver), the vascular network - in both VCC and IHC datasets - was automatically segmented and/or morphologically analysed. Our methodological framework allows 3D reconstruction and quantification of the hepatic circulation, ranging from the major blood vessels down to the intertwined and interconnected sinusoids. We believe that the presented framework will have value beyond studies of the liver, and will facilitate a better understanding of various parenchymal organs in general, in physiological and pathological circumstances.

Authors: Geert Peeters, Charlotte Debbaut, Wim Laleman, Adrian Friebel, Diethard Monbaliu, Ingrid Vander Elst, Jan R Detrez, Tim Vandecasteele, Tim Johann, Thomas De Schryver, Luc Van Hoorebeke, Kasper Favere, Jonas Verbeke, Dirk Drasdo, Stefan Hoehme, Patrick Segers, Pieter Cornillie, Winnok H De Vos

Date Published: 28th Dec 2016

Journal: Journal of anatomy

CYP2E1 recovery is associated with a pericentral fibrosis pattern after repeated CCl4 insults
Chronic Liver Disease Progression (LiSyM-DP - Pillar II)

Abstract

Not specified

Authors: Seddik Hammad, Jieling Zhao, Yi Yin, Ayham Zaza, Dirk Drasdo, Jan Hengstler, Steven Dooley

Date Published: 2019

Journal: Not specified

Bile micro-infarcts in cholestasis are initiated by rupture of the apical hepatocyte membrane and cause shunting of bile to sinusoidal blood
Model Guided Pharmacotherapy In Chronic Liver Disease (LiSyM-MGP)

Abstract

Not specified

Authors: Ahmed Ghallab, Ute Hofmann, Selahaddin Sezgin, Nachiket Vartak, Reham Hassan, Ayham Zaza, Patricio Godoy, Kai Markus Schneider, Georgia Guenther, Yasser A Ahmed, Aya A Abbas, Verena Keitel, Lars Kuepfer, Steven Dooley, Frank Lammert, Christian Trautwein, Michael Spiteller, Dirk Drasdo, Alan F Hofmann, Peter Jansen, Jan Hengstler, Raymond Reif

Date Published: 13th Aug 2018

Journal: HEP

Quantitative analysis of hepatic macro- and microvascular alterations during cirrhogenesis in the rat.
Early Metabolic Injury (LiSyM-EMI - Pillar I)

Abstract (Expand)

Cirrhosis represents the end-stage of any persistent chronically active liver disease. It is characterized by the complete replacement of normal liver tissue by fibrosis, regenerative nodules, and … complete fibrotic vascularized septa. The resulting angioarchitectural distortion contributes to an increasing intrahepatic vascular resistance, impeding liver perfusion and leading to portal hypertension. To date, knowledge on the dynamically evolving pathological changes of the hepatic vasculature during cirrhogenesis remains limited. More specifically, detailed anatomical data on the vascular adaptations during disease development is lacking. To address this need, we studied the 3D architecture of the hepatic vasculature during induction of cirrhogenesis in a rat model. Cirrhosis was chemically induced with thioacetamide (TAA). At predefined time points, the hepatic vasculature was fixed and visualized using a combination of vascular corrosion casting and deep tissue microscopy. Three-dimensional reconstruction and data-fitting enabled cirrhogenic features to extracted at multiple scales, portraying the impact of cirrhosis on the hepatic vasculature. At the macrolevel, we noticed that regenerative nodules severely compressed pliant venous vessels from 12 weeks of TAA intoxication onwards. Especially hepatic veins were highly affected by this compression, with collapsed vessel segments severely reducing perfusion capabilities. At the microlevel, we discovered zone-specific sinusoidal degeneration, with sinusoids located near the surface being more affected than those in the middle of a liver lobe. Our data shed light on and quantify the evolving angioarchitecture during cirrhogenesis. These findings may prove helpful for future targeted invasive interventions.

Authors: G. Peeters, C. Debbaut, A. Friebel, P. Cornillie, W. H. De Vos, K. Favere, I. Vander Elst, T. Vandecasteele, Tim Johann, L. Van Hoorebeke, D. Monbaliu, Dirk Drasdo, Stefan Hoehme, W. Laleman, P. Segers

Date Published: 4th Dec 2017

Journal: J Anat

Quantifying Tissue Mechanics and Tissue Formation with High Resolution Models
Chronic Liver Disease Progression (LiSyM-DP - Pillar II)
No description specified

Creators: Tim Johann, Dirk Drasdo, Stefan Hoehme, Paul Van Liedekerke, Johannes Neitsch

Contributor: Tim Johann

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TiSim - A Workbench and Framework for Biophysical Agent-Based Multi-Scale Multi-Cellular Models.
Chronic Liver Disease Progression (LiSyM-DP - Pillar II)

Computational models complement experimental methods in the analysis of tissue organization processes, and play an increasingly important role in systems biology and systems medicine. Creating and parameterizing mathematical models for the simulation of biological tissue dynamics at multiple scales is still a complex and resource-consuming task, which necessitates skills in diverse scientific disciplines. The software TiSim was conceived to facilitate programming, integration and deployment of
...

Creators: Tim Johann, Jieling Zhao, Stefan Hoehme, Dirk Drasdo, Andreas Buttenschön, Noémie Boissier, Géraldine Cellière, Paul Van Liedekerke, Johannes Neitsch

Contributor: Tim Johann

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Poster 17 Mid-Term Evaluation - Drasdo - Pillar II & III
Chronic Liver Disease Progression (LiSyM-DP - Pillar II), Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III), LiSyM network
No description specified

Creators: Tim Johann, Dirk Drasdo, Ayham Zaza, Jieling Zhao, Paul Van Liedekerke

Contributor: Tim Johann

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Presentation Mid-Term Evaluation Drasdo Pillar II
Chronic Liver Disease Progression (LiSyM-DP - Pillar II), LiSyM network
No description specified

Creators: Tim Johann, Dirk Drasdo

Contributor: Tim Johann

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Presentation Mid-Term Evaluation Drasdo/Hengstler Pillar III
Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III), LiSyM network
No description specified

Creators: Tim Johann, Dirk Drasdo, Jan Hengstler

Contributor: Tim Johann

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