Christian Holland

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About Christian Holland:

PhD student at Joint Research Center for Computational Biomedicine (JRC-COMBINE)

SEEK ID: https://seek.lisym.org/people/25

Location: Germany

ORCID: https://orcid.org/0000-0002-3060-5786

Joined: 2nd May 2017

Expertise: Not specified

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LiSyM: Liver Systems Medicine

Liver Systems Medicine : striving to develop non-invasive methods for diagnosing and treating NAFLD by combining mathematical modeling and biological research. LiSyM, is a multidisciplinary research network, in which molecular and cell biologists, clinical researchers, pharmacologists and experts in mathematical modeling examine the liver in its entirety. LiSyM research focuses on the metabolic liver disease non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis ...

Projects: LiSyM Core Infrastructure and Management (LiSyM-PD), LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi), Model Guided Pharmacotherapy In Chronic Liver Disease (LiSyM-MGP), Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM), The Hedgehog Signalling Pathway (LiSyM-JGMMS), Multi-Scale Models for Personalized Liver Function Tests (LiSyM-MM-PLF), LiSyM PALs, Project Management PTJ, LiSyM network, LiSyM Scientific Leadership Team (LiSyM-LT)

Web page: https://www.lisym.org/

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LiSyM network

This comprises the whole LiSyM network

Programme: LiSyM: Liver Systems Medicine

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

Start date: 1st Jan 2016

Organisms: Rattus norvegicus, Rattus rattus, Mus musculus, Homo sapiens

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

In one in five people with NAFLD, the functioning liver cells, the hepatocytes, are replaced by connective tissue. Eventually this fibrosis becomes irreversible. In this state the liver is like a ‘scar that never heals’. Through it, the liver loses many of its vital functions. LiSyM-Pillar II wants to know more about which factors promote fibrosis and the conditions under which fibrosis becomes irreversible How can fibrosis be diagnosed as early as possible? Researchers in the pillar are also ...

Programme: LiSyM: Liver Systems Medicine

Public web page: http://www.lisym.org/our-work/pillar-research

Start date: 1st Jan 2016

Organisms: Mus musculus, Rattus rattus, Rattus norvegicus, Homo sapiens

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RWTH Aachen University Hospital - Joint Research Center for Computational Biomedicine

Country: Germany

City: 52074 Aachen

Web page: https://www.ukaachen.de/kliniken-institute/joint-research-center-for-computational-biomedicine.html

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Robustness and applicability of transcription factor and pathway analysis tools on single-cell RNA-seq data

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

GitHub repository containing the analysis code

Creator: Christian Holland

Submitter: Christian Holland

Investigations: No Investigations

Studies: No Studies

Assays: No Assays

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Created: 14th Feb 2020 at 12:33

Transfer of regulatory knowledge from human to mouse for functional genomics analysis

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

GitHub repository that contains all analyses scripts to reproduce the results reported in "Transfer of regulatory knowledge from human to mouse for functional genomics analysis"

Creator: Christian Holland

Submitter: Christian Holland

Investigations: No Investigations

Studies: No Studies

Assays: No Assays

Created: 30th Jan 2020 at 16:28

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Tolerance of repeated toxic injuries of murine livers is associated with steatosis and inflammation

LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM network, C-TIP-HCC network

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Abstract (Expand)

Abstract The human liver has a remarkable capacity to regenerate and thus compensate over decades for fibrosis caused by toxic chemicals, drugs, alcohol, or malnutrition. To date, no protective mechanisms …

Authors: Seddik Hammad, Christoph Ogris, Amnah Othman, Pia Erdoesi, Wolfgang Schmidt-Heck, Ina Biermayer, Barbara Helm, Yan Gao, Weronika Piorońska, Christian H. Holland, Lorenza A. D’Alessandro, Carolina de la Torre, Carsten Sticht, Sherin Al Aoua, Fabian J. Theis, Heike Bantel, Matthias P. Ebert, Ursula Klingmüller, Jan G. Hengstler, Steven Dooley, Nikola S. Mueller

Date Published: 1st Jul 2023

Publication Type: Journal

DOI: 10.1038/s41419-023-05855-4

Citation: Cell Death Dis 14(7),414

Created: 12th Jul 2023 at 13:09, Last updated: 8th Mar 2024 at 07:44

Spatio-Temporal Multiscale Analysis of Western Diet-Fed Mice Reveals a Translationally Relevant Sequence of Events during NAFLD Progression

LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF)

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Mouse models of non-alcoholic fatty liver disease (NAFLD) are required to define therapeutic targets, but detailed time-resolved studies to establish a sequence of events are lacking. Here, we fed male …

Authors: Ahmed Ghallab, Maiju Myllys, Adrian Friebel, Julia Duda, Karolina Edlund, Emina Halilbasic, Mihael Vucur, Zaynab Hobloss, Lisa Brackhagen, Brigitte Begher-Tibbe, Reham Hassan, Michael Burke, Erhan Genc, Lynn Johann Frohwein, Ute Hofmann, Christian H. Holland, Daniela González, Magdalena Keller, Abdel-latif Seddek, Tahany Abbas, Elsayed S. I. Mohammed, Andreas Teufel, Timo Itzel, Sarah Metzler, Rosemarie Marchan, Cristina Cadenas, Carsten Watzl, Michael A. Nitsche, Franziska Kappenberg, Tom Luedde, Thomas Longerich, Jörg Rahnenführer, Stefan Hoehme, Michael Trauner, Jan G. Hengstler

Date Published: 1st Oct 2021

Publication Type: Journal

DOI: 10.3390/cells10102516

Citation: Cells 10(10):2516

Created: 22nd Jul 2024 at 16:01, Last updated: 22nd Jul 2024 at 16:01

Transcriptomic Cross‐Species Analysis of Chronic Liver Disease Reveals Consistent Regulation Between Humans and Mice

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

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Abstract

Not specified

Authors: Christian H. Holland, Ricardo O. Ramirez Flores, Maiju Myllys, Reham Hassan, Karolina Edlund, Ute Hofmann, Rosemarie Marchan, Cristina Cadenas, Jörg Reinders, Stefan Hoehme, Abdel‐latif Seddek, Steven Dooley, Verena Keitel, Patricio Godoy, Brigitte Begher‐Tibbe, Christian Trautwein, Christian Rupp, Sebastian Mueller, Thomas Longerich, Jan G. Hengstler, Julio Saez‐Rodriguez, Ahmed Ghallab

Date Published: 28th Aug 2021

Publication Type: Journal

DOI: 10.1002/hep4.1797

Citation: Hepatol Commun,hep4.1797

Created: 28th Aug 2021 at 09:39, Last updated: 8th Mar 2024 at 07:44

Hepatocyte-specific NRF2 activation controls fibrogenesis and carcinogenesis in steatohepatitis.

LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

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BACKGROUND & AIMS: In chronic liver diseases, inflammation induces oxidative stress and thus may contribute to the progression of liver injury, fibrosis, and carcinogenesis. The KEAP1/NRF2 axis is … a major regulator of cellular redox balance. In the present study, we investigated whether the KEAP1/NRF2 system is involved in liver disease progression in humans and mice. METHODS: The clinical relevance of oxidative stress was investigated by liver RNA sequencing in a well-characterized cohort of patients with non-alcoholic fatty liver disease (n = 63) and correlated with histological and clinical parameters. For functional analysis, hepatocyte-specific Nemo knockout (NEMO(Deltahepa)) mice were crossed with hepatocyte-specific Keap1 knockout (KEAP1(Deltahepa)) mice. RESULTS: Immunohistochemical analysis of human liver sections showed increased oxidative stress and high NRF2 expression in patients with chronic liver disease. RNA sequencing of liver samples in a human pediatric NAFLD cohort revealed a significant increase of NRF2 activation correlating with the grade of inflammation, but not with the grade of steatosis, which could be confirmed in a second adult NASH cohort. In mice, microarray analysis revealed that Keap1 deletion induces NRF2 target genes involved in glutathione metabolism and xenobiotic stress (e.g., Nqo1). Furthermore, deficiency of one of the most important antioxidants, glutathione (GSH), in NEMO(Deltahepa) livers was rescued after deleting Keap1. As a consequence, NEMO(Deltahepa)/KEAP1(Deltahepa) livers showed reduced apoptosis compared to NEMO(Deltahepa) livers as well as a dramatic downregulation of genes involved in cell cycle regulation and DNA replication. Consequently, NEMO(Deltahepa)/KEAP1(Deltahepa) compared to NEMO(Deltahepa) livers displayed decreased fibrogenesis, lower tumor incidence, reduced tumor number, and decreased tumor size. CONCLUSIONS: NRF2 activation in patients with non-alcoholic steatohepatitis correlates with the grade of inflammation, but not steatosis. Functional analysis in mice demonstrated that NRF2 activation in chronic liver disease is protective by ameliorating fibrogenesis, initiation and progression of hepatocellular carcinogenesis. LAY SUMMARY: The KEAP1 (Kelch-like ECH-associated protein-1)/NRF2 (erythroid 2-related factor 2) axis has a major role in regulating cellular redox balance. Herein, we show that NRF2 activity correlates with the grade of inflammation in patients with non-alcoholic steatohepatitis. Functional studies in mice actually show that NRF2 activation, resulting from KEAP1 deletion, protects against fibrosis and cancer.

Authors: A. Mohs, T. Otto, K. M. Schneider, M. Peltzer, M. Boekschoten, C. H. Holland, C. A. Hudert, L. Kalveram, S. Wiegand, J. Saez-Rodriguez, T. Longerich, J. G. Hengstler, C. Trautwein

Date Published: 22nd Dec 2020

Publication Type: Journal

PubMed ID: 33342543

Citation: J Hepatol. 2021 Mar;74(3):638-648. doi: 10.1016/j.jhep.2020.09.037. Epub 2020 Oct 24.

Created: 29th Jun 2021 at 17:25, Last updated: 8th Mar 2024 at 07:44

Robustness and applicability of transcription factor and pathway analysis tools on single-cell RNA-seq data

LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM network

Abstract (Expand)

Background Many functional analysis tools have been developed to extract functional and mechanistic insight from bulk transcriptome data. With the advent of single-cell RNA sequencing (scRNA-seq), it …

Authors: Christian H. Holland, Jovan Tanevski, Javier Perales-Patón, Jan Gleixner, Manu P. Kumar, Elisabetta Mereu, Brian A. Joughin, Oliver Stegle, Douglas A. Lauffenburger, Holger Heyn, Bence Szalai, Julio Saez-Rodriguez