Manuel Winkler

ORCID: 0000-0003-2415-9350
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About
Contact & Profiles
Research Areas
  • Liver physiology and pathology
  • Public Administration and Political Analysis
  • Pancreatic function and diabetes
  • Physics and Engineering Research Articles
  • Sociology and Education Studies
  • German Literature and Culture Studies
  • Cancer Cells and Metastasis
  • Kruppel-like factors research
  • Autism Spectrum Disorder Research
  • Cellular transport and secretion
  • Liver Disease Diagnosis and Treatment
  • Cardiac Fibrosis and Remodeling
  • Wnt/β-catenin signaling in development and cancer
  • Organ Transplantation Techniques and Outcomes
  • Genetics and Neurodevelopmental Disorders
  • Developmental Biology and Gene Regulation
  • Mechanisms of cancer metastasis
  • Immune cells in cancer
  • Renal and related cancers
  • Innovation, Technology, and Society
  • Congenital heart defects research
  • Cancer Genomics and Diagnostics
  • Signaling Pathways in Disease
  • Epigenetics and DNA Methylation
  • Pulmonary Hypertension Research and Treatments

University Hospital Heidelberg
2013-2025

University Medical Centre Mannheim
2015-2025

Heidelberg University
2013-2025

Oncoscience (Germany)
2024-2025

University Medical Center
2024

Innsbruck Medical University
2021-2024

Universität Innsbruck
2021-2024

Fibrosis is a hallmark of chronic disease. Although fibroblasts are involved, it unclear to what extent endothelial cells also might contribute. We detected increased expression the transcription factor Sox9 in several different mouse fibrosis models. These models included systolic heart failure induced by pressure overload, diastolic high-fat diet and nitric oxide synthase inhibition, pulmonary bleomycin treatment, liver due choline-deficient diet. observed up-regulation SOX9 cardiac tissue...

10.1126/scitranslmed.abq4581 article EN Science Translational Medicine 2024-02-28

Angiocrine signaling by liver sinusoidal endothelial cells (LSECs) regulates hepatic functions such as growth, metabolic maturation, and regeneration. Recently, we identified GATA4 the master regulator of LSEC specification during development. Herein, studied role in adult pathogenesis.We generated Clec4g-icretg/0xGata4fl/fl (Gata4LSEC-KO) mice with LSEC-specific depletion Gata4. Livers were analyzed histology, electron microscopy, immunohistochemistry/immunofluorescence, situ hybridization,...

10.1016/j.jhep.2020.08.033 article EN cc-by-nc-nd Journal of Hepatology 2020-09-09

The interaction of tumor cells with organ-specific endothelial (EC) is an important step during metastatic progression. Notch signaling in niches has been implicated mediating opposing effects on organotropic metastasis to the lungs and liver, respectively. In this study, we scrutinized role activation liver metastasis. To target hepatic EC (HEC), a novel subtype-specific Cre driver mouse was generated. Clec4g-Cretg/wt mice were crossed Rosa26N1ICD-IRES-GFP enhance HEC (NICDOE-HEC)....

10.1158/0008-5472.can-18-1752 article EN Cancer Research 2018-12-10

Background and Aims: In hereditary hemorrhagic telangiectasia (HHT), severe liver vascular malformations are associated with mutations in the Activin A Receptor‐Like Type 1 ( ACVRL1 ) gene encoding ALK1, receptor for bone morphogenetic protein (BMP) 9/BMP10, which regulates blood vessel development. Here, we established an HHT mouse model exclusive involvement adequate life expectancy to investigate ALK1 signaling formation metabolic function. Approach Results: Liver sinusoidal endothelial...

10.1002/hep.32641 article EN Hepatology 2022-07-01

Abstract Liver sinusoidal endothelial cells (LSECs) critically regulate homeostatic liver function and pathogenesis. However, the isolation of LSECs remains a major technological bottleneck in studying molecular mechanisms governing LSEC functions. Current techniques to isolate LSECs, relying on perfusion-dependent digestion, are cumbersome with limited throughput. We here describe perfusion-independent high-throughput procedure high purity. Indifferently from previous approaches, chopped...

10.1038/s42003-025-07458-5 article EN cc-by Communications Biology 2025-01-08

In malignant melanoma, liver metastases significantly reduce survival, even despite highly effective new therapies. Given the increase in metabolic diseases such as dysfunction-associated steatotic disease (MASLD) and steatohepatitis (MASH), this study investigated impact of sinusoidal endothelial cell (LSEC)-specific alterations MASLD/MASH on hepatic melanoma metastasis. Mice were fed a choline-deficient L-amino acid-defined (CDAA) diet for ten weeks to induce MASH-associated fibrosis, or...

10.1186/s40170-025-00374-6 article EN cc-by Cancer & Metabolism 2025-01-28

Abstract Within the bone marrow microenvironment, endothelial cells (EC) exert important functions. Arterial EC support hematopoiesis while H-type capillaries induce formation. Here, we show that BM sinusoidal (BM-SEC) actively control erythropoiesis. Mice with stabilized β-catenin in BM-SEC ( Ctnnb1 OE-SEC ) generated by using a BM-SEC-restricted Cre mouse line Stab2-iCreF3 develop fatal anemia. While activation of Wnt-signaling causes an increase erythroblast subsets (PII–PIV), mature...

10.1038/s41467-021-27161-3 article EN cc-by Nature Communications 2021-11-29

Abstract Pianp (also known as Leda-1) is a type I transmembrane protein with preferential expression in the mammalian CNS. Its processing characterized by proteolytic cleavage range of proteases including Adam10, Adam17, MMPs, and γ-secretase complex. can interact Pilrα GB1a subunit GABA B receptor (GBR) A recent case description boy global developmental delay homozygous nonsense variant PIANP supports hypothesis that involved control behavioral traits mammals. To investigate physiological...

10.1038/s41380-019-0519-9 article EN cc-by Molecular Psychiatry 2019-09-11

Abstract Background Cutaneous melanoma exhibits heterogeneous metastatic patterns and prognosis. In this regard, liver metastasis, which is detected in ~ 10–20% of stage 4 patients, came to the fore research, as it recently evolved decisive indicator treatment resistance immune checkpoint inhibition. Methods Hepatic metastases were induced by intrasplenic injection five different murine cell lines. The efficiencies hepatic colonization, morphologic patterns, gene expression profiles degree...

10.1186/s12967-022-03255-4 article EN cc-by Journal of Translational Medicine 2022-02-02

Objectives Sodium magnetic resonance (MR) imaging provides noninvasive insights to cellular processes by measuring tissue sodium concentration (TSC). Many clinical studies combine MR with standard procedures, in which contrast media is frequently administered. This work investigates the influence of gadolinium-based agents on quantification TSC. Thus, either scan pauses between early and late contrast-enhanced acquisitions can be used efficiently or performed as final after dynamic...

10.1097/rli.0000000000000487 article EN Investigative Radiology 2018-05-31

BackgroundOpen pneumothorax after a penetrating thorax trauma is life-threatening disease with high mortality. An emergency application of chest seal (CS) allowing the release trapped air optimum initial therapy until surgical drainage available.MethodsIn newly developed experimental porcine model open pneumothorax, we tested 3 different materials regarding their applicability for acute treatment sucking wounds in prehospital care, namely commonly used rescue blanket (RB), plastic foil from...

10.1016/j.athoracsur.2021.06.083 article EN cc-by The Annals of Thoracic Surgery 2021-08-08

Endothelial wingless-related integration site (Wnt)-/β-catenin signaling is a key regulator of the tightly sealed blood–brain barrier. In hepatic vascular niche angiokine-mediated Wnt was recently identified as an important hepatocyte function, including determination final adult liver size, regeneration, and metabolic zonation. Within vasculature, sinusoidal endothelial cells (LSECs) are morphologically unique functionally specialized microvascular (ECs). Pathological changes LSECs involved...

10.3389/fphys.2021.722394 article EN cc-by Frontiers in Physiology 2021-09-29

<title>Abstract</title> Formation of liver fibrosis patterns is a complex process that can only be marginally investigated experimentally<italic>.</italic> A digital twin (DT), computational model the liver, warranted, as it permits integration and modulation multiple mechanisms. We develop DT on chronic injury-mediated formation CCl<sub>4</sub>-induced septal based experimental iterations. This closely reproduces spatial-temporal pattern hepatocytes, hepatic stellate cells (HSCs),...

10.21203/rs.3.rs-3911195/v1 preprint EN cc-by Research Square (Research Square) 2024-08-23

Summary Liver sinusoidal endothelial cells (LSECs) critically regulate homeostatic liver function and pathogenesis. However, the isolation of LSECs remains a major technological bottleneck in studying molecular mechanisms governing LSEC functions. Current techniques to isolate LSECs, relying on perfusion-dependent digestion, are cumbersome with limited throughput. We here describe perfusion-independent high-throughput procedure high purity. Indifferently from previous approaches, chopped...

10.1101/2024.03.11.584492 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2024-03-14
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