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Jochen Hampe

About Jochen Hampe:
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SEEK ID: https://seek.lisym.org/people/56

Location: Germany

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LiSyM network

This comprises the whole LiSyM network

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

Early Metabolic Injury (LiSyM-EMI - Pillar I)

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. LiSyM-EMI looks into the transition from steatosis to non-alcoholic steatohepatitis (NASH) as the disease-defining moment in NAFLD. A systems analysis of these early disease events will be performed to elucidate the molecular mechanisms that trigger disease establishment.

Public web page: Not specified

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

Mouse expression dataset (Comparison of Gene Expression Patterns Between Mouse Models of Nonalcoholic Fatty Liver Disease and Liver Tissues From Patients.)
Early Metabolic Injury (LiSyM-EMI - Pillar I)

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Mouse models of NAFLD have been used in studies of pathogenesis and treatment, and have certain features of the human disease. We performed a systematic transcriptome-wide analysis of liver tissues from patients at different stages of NAFLD progression (ranging from healthy obese individuals to those with steatosis), as well as rodent models of NAFLD, to identify
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Creators: Mario Brosch, Jochen Hampe, Clemens Schafmayer, Witigo Von Schönfels

Contributor: Mario Brosch

Human expression dataset (Comparison of Gene Expression Patterns Between Mouse Models of Nonalcoholic Fatty Liver Disease and Liver Tissues From Patients.)
Early Metabolic Injury (LiSyM-EMI - Pillar I)

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Mouse models of NAFLD have been used in studies of pathogenesis and treatment, and have certain features of the human disease. We performed a systematic transcriptome-wide analysis of liver tissues from patients at different stages of NAFLD progression (ranging from healthy obese individuals to those with steatosis), as well as rodent models of NAFLD, to identify
...

Creators: Mario Brosch, Jochen Hampe, Clemens Schafmayer, Witigo Von Schönfels

Contributor: Mario Brosch

Mutual Zonated Interactions of Wnt and Hh Signaling Are Orchestrating the Metabolism of the Adult Liver in Mice and Human
Early Metabolic Injury (LiSyM-EMI - Pillar I)

Abstract (Expand)

The Hedgehog (Hh) and Wnt/β-Catenin (Wnt) cascades are morphogen pathways whose pronounced influence on adult liver metabolism has been identified in recent years. How both pathways communicate and … control liver metabolic functions are largely unknown. Detecting core components of Wnt and Hh signaling and mathematical modeling showed that both pathways in healthy liver act largely complementary to each other in the pericentral (Wnt) and the periportal zone (Hh) and communicate mainly by mutual repression. The Wnt/Hh module inversely controls the spatiotemporal operation of various liver metabolic pathways, as revealed by transcriptome, proteome, and metabolome analyses. Shifting the balance to Wnt (activation) or Hh (inhibition) causes pericentralization and periportalization of liver functions, respectively. Thus, homeostasis of the Wnt/Hh module is essential for maintaining proper liver metabolism and to avoid the development of certain metabolic diseases. With caution due to minor species-specific differences, these conclusions may hold for human liver as well.

Authors: Erik Kolbe, Susanne Aleithe, Christiane Rennert, Luise Spormann, Fritzi Ott, David Meierhofer, Robert Gajowski, Claus Stöpel, Stefan Hoehme, Michael Kücken, Lutz Brusch, Michael Seifert, Witigo Von Schönfels, Clemens Schafmayer, Mario Brosch, Ute Hofmann, Georg Damm, Daniel Seehofer, Jochen Hampe, Rolf Gebhardt, Madlen Matz-Soja

Date Published: 1st Dec 2019

Journal: Cell Reports

Three-dimensional spatially resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression.
Early Metabolic Injury (LiSyM-EMI - Pillar I), LiSyM network

Abstract (Expand)

Early disease diagnosis is key to the effective treatment of diseases. Histopathological analysis of human biopsies is the gold standard to diagnose tissue alterations. However, this approach has low … resolution and overlooks 3D (three-dimensional) structural changes resulting from functional alterations. Here, we applied multiphoton imaging, 3D digital reconstructions and computational simulations to generate spatially resolved geometrical and functional models of human liver tissue at different stages of non-alcoholic fatty liver disease (NAFLD). We identified a set of morphometric cellular and tissue parameters correlated with disease progression, and discover profound topological defects in the 3D bile canalicular (BC) network. Personalized biliary fluid dynamic simulations predicted an increased pericentral biliary pressure and micro-cholestasis, consistent with elevated cholestatic biomarkers in patients' sera. Our spatially resolved models of human liver tissue can contribute to high-definition medicine by identifying quantitative multiparametric cellular and tissue signatures to define disease progression and provide new insights into NAFLD pathophysiology.

Authors: Fabian Segovia Miranda, H. Morales-Navarrete, Michael Kücken, Vincent Moser, S. Seifert, U. Repnik, Fabian Rost, Mario Brosch, A. Hendricks, S. Hinz, C. Rocken, D. Lutjohann, Y. Kalaidzidis, Clemens Schafmayer, Lutz Brusch, Jochen Hampe, Marino Zerial

Date Published: 2nd Dec 2019

Journal: Nat Med

Electrosurgical liver resection has a superior regeneration outcome as compared to en-bloc ligation in a novel model of partial hepatectomy in mice
Early Metabolic Injury (LiSyM-EMI - Pillar I)

Abstract (Expand)

Background: The extent of resection and the frequency of liver surgery have increased over the past decades, enabled by improved haemostasis provided by electrosurgical liver dissection. Because extensive … liver surgery is still associated with lethal complications, further optimisation of the technique and a better molecular understanding of hepatic wound healing and regeneration are needed. Systematic studies and a mouse model reflecting the clinical reality of liver surgery are lacking. Methods: We performed liver resection in mice with a monopolar electrocautery device in comparison to the classical en-bloc ligation method. Regeneration was assessed using liver weight and BrDU immunohistochemistry after sacrifice and non-invasively using micro computed tomography (µCT). Results: Mortality in the electrosurgical model was similar to the ligation method given an identical extent of resection. Regeneration of liver proceeded significantly faster in the electrosurgical group: Liver weight was 25.6% higher at sacrifice after 168h (p=0.0003). Concordantly, both µCT analysis (22.6% higher liver volume at 168h, p=0.008) and BrDU staining (71.4% higher proliferation at 72h, p=0.0005) indicated superior regeneration of liver after electrosurgical partial hepatectomy. Conclusions: The mode of liver resection has a profound impact on regeneration and should be studied molecularly using the presented novel model of electrosurgical liver resection.

Authors: W. von Schonfels, Clemens Schafmayer, Jochen Hampe

Date Published: 27th Jan 2018

Journal: prepublication

Wet-tip versus dry-tip regimes of osmotically driven fluid flow
Early Metabolic Injury (LiSyM-EMI - Pillar I)

Abstract (Expand)

The secretion of osmolytes into a lumen and thereby caused osmotic water inflow can drive fluid flows in organs without a mechanical pump. Such fluids include saliva, sweat, pancreatic juice and bile. … The effects of elevated fluid pressure and the associated mechanical limitations of organ function remain largely unknown since fluid pressure is difficult to measure inside tiny secretory channels in vivo. We consider the pressure profile of the coupled osmolyte-flow problem in a secretory channel with a closed tip and an open outlet. Importantly, the entire lateral boundary acts as a dynamic fluid source, the strength of which self-organizes through feedback from the emergent pressure solution itself. We derive analytical solutions and compare them to numerical simulations of the problem in three-dimensional space. The theoretical results reveal a phase boundary in a four-dimensional parameter space separating the commonly considered regime with steady flow all along the channel, here termed “wet-tip” regime, from a “dry-tip” regime suffering ceased flow downstream from the closed tip. We propose a relation between the predicted phase boundary and the onset of cholestasis, a pathological liver condition with reduced bile outflow. The phase boundary also sets an intrinsic length scale for the channel which could act as a length sensor during organ growth.

Authors: Oleksandr Ostrenko, Jochen Hampe, Lutz Brusch

Date Published: 1st Dec 2019

Journal: Sci Rep

Evolutionary Distance Predicts Recurrence After Liver Transplantation in Multifocal Hepatocellular Carcinoma.
Early Metabolic Injury (LiSyM-EMI - Pillar I)

Abstract (Expand)

BACKGROUND: Liver transplantation (LTx) is a potentially curative treatment option for hepatocellular carcinoma (HCC) in cirrhosis. However, patients, where HCC is already a systemic disease, LTx may … be individually harmful and has a negative impact on donor organ usage. Thus, there is a need for improved selection criteria beyond nodule morphology to select patients with a favorable outcome for LTx in multifocal HCC. Evolutionary distance measured from genome-wide single-nucleotide polymorphism data between tumor nodules and the cirrhotic liver may be a prognostic marker of survival after LTx for multifocal HCC. METHODS: In a retrospective multicenter study, clinical data and formalin-fixed paraffin-embedded specimens of the liver and 2 tumor nodules were obtained from explants of 30 patients in the discovery and 180 patients in the replication cohort. DNA was extracted from formalin-fixed paraffin-embedded specimens followed by genome wide single-nucleotide polymorphism genotyping. RESULTS: Genotype quality criteria allowed for analysis of 8 patients in the discovery and 17 patients in the replication set. DNA concentrations of a total of 25 patients fulfilled the quality criteria and were included in the analysis. Both, in the discovery (P = 0.04) and in the replication data sets (P = 0.01), evolutionary distance was associated with the risk of recurrence of HCC after transplantation (combined P = 0.0002). In a univariate analysis, evolutionary distance (P = 7.4 x 10) and microvascular invasion (P = 1.31 x 10) were significantly associated with survival in a Cox regression analysis. CONCLUSIONS: Evolutionary distance allows for the determination of a high-risk group of recurrence if preoperative liver biopsy is considered.

Authors: N. Heits, Mario Brosch, A. Herrmann, R. Behrens, C. Rocken, H. Schrem, A. Kaltenborn, J. Klempnauer, H. H. Kreipe, B. Reichert, C. Lenschow, C. Wilms, T. Vogel, H. Wolters, E. Wardelmann, D. Seehofer, S. Buch, S. Zeissig, S. Pannach, N. Raschzok, M. Dietel, W. von Schoenfels, S. Hinz, A. Teufel, M. Evert, A. Franke, Ann-Kristin Becker, F. Braun, Jochen Hampe, Clemens Schafmayer

Date Published: 12th Jul 2018

Journal: Transplantation

Poster 8 LiSyM-Midterm_Evaluation_Hampe
Early Metabolic Injury (LiSyM-EMI - Pillar I), LiSyM network
No description specified

Creators: Mario Brosch, Jochen Hampe

Contributor: Mario Brosch

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