A5044349374- Liver Disease Diagnosis and Treatment
- Telomeres, Telomerase, and Senescence
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Dietary Effects on Health
- PARP inhibition in cancer therapy
- Epigenetics and DNA Methylation
- Diabetes and associated disorders
- Pediatric Hepatobiliary Diseases and Treatments
- Metabolism and Genetic Disorders
- Pharmacogenetics and Drug Metabolism
- Cancer-related Molecular Pathways
- Computational Drug Discovery Methods
- RNA regulation and disease
- Hepatocellular Carcinoma Treatment and Prognosis
- Inflammasome and immune disorders
- Lipid metabolism and disorders
- Cell death mechanisms and regulation
- Lung Cancer Treatments and Mutations
- Endoplasmic Reticulum Stress and Disease
- Drug Transport and Resistance Mechanisms
- Pancreatitis Pathology and Treatment
- MicroRNA in disease regulation
- interferon and immune responses
- Diet, Metabolism, and Disease
- Diet and metabolism studies
Heidelberg University
2021-2025
German Cancer Research Center
2021-2024
DKFZ-ZMBH Alliance
2023
Riyadh Elm University
2019
It is currently not well known how necroptosis and responses manifest in vivo. Here, we uncovered a molecular switch facilitating reprogramming between two alternative modes of signaling hepatocytes, fundamentally affecting immune hepatocarcinogenesis. Concomitant necrosome NF-κB activation which physiologically express low concentrations receptor-interacting kinase 3 (RIPK3), did lead to immediate cell death but forced them into prolonged "sublethal" state with leaky membranes, functioning...
Abstract Cellular senescence is a stress response with broad pathophysiological implications. Senotherapies can induce to treat cancer or eliminate senescent cells ameliorate ageing and age-related pathologies. However, the success of senotherapies limited by lack reliable ways identify senescence. Here, we use nuclear morphology features devise machine-learning classifiers that accurately predict induced diverse stressors in different cell types tissues. As proof-of-principle, these...
The role and molecular mechanisms of intermittent fasting (IF) in non-alcoholic steatohepatitis (NASH) its transition to hepatocellular carcinoma (HCC) are unknown. Here, we identified that an IF 5:2 regimen prevents NASH development as well ameliorates established fibrosis without affecting total calorie intake. Furthermore, the blunted NASH-HCC when applied therapeutically. timing, length, number cycles type diet were critical parameters determining benefits fasting. Combined proteome,...
Abstract Inhibition of S6 kinase 1 (S6K1) extends lifespan and improves healthspan in mice, but the underlying mechanisms are unclear. Cellular senescence is a stable growth arrest accompanied by an inflammatory senescence-associated secretory phenotype (SASP). SASP-mediated chronic inflammation contribute to age-related pathology, specific role S6K1 has not been determined. Here we show that deletion does reduce ameliorates aged mouse livers. Using human models senescence, demonstrate...
Abstract Cell fate plasticity enables development, yet unlocked is a cancer hallmark. While transcription master regulators induce lineage-specific genes to restrict plasticity, it remains unclear whether actively suppressed by repressors. Here we computationally predict so-called safeguard repressors for 18 cell types that block phenotypic lifelong. We validated hepatocyte-specific candidates using reprogramming, revealing prospero homeobox protein 1 (PROX1) enhanced hepatocyte identity...
C57BL/6 mice are widely used for metabolic, cancer, and immunologic studies. High-caloric diets induce a heterogeneous phenotype in mice, with the majority developing obesity metabolic syndrome, while others remain lean metabolically healthy.1Burcelin R. et al.Am J Physiol Endocrinol Metab. 2002; 282: 834-842Crossref PubMed Scopus (235) Google Scholar Western (WDs), methionine-deficient or choline deficient–based to study nonalcoholic fatty liver disease steatohepatitis (NASH), important...
ABSTRACT Inhibition of the nutrient-responsive mTOR (mammalian target rapamycin) signalling pathway including key downstream effector S6 kinase 1 (S6K1) extends lifespan and improves healthspan in mice. However, underlying mechanisms contributing to broad range age-related benefits observed with loss S6K1 are unclear. Cellular senescence is a stable growth arrest accompanied by an inflammatory phenotype (termed senescence-associated secretory phenotype, or SASP). While both cellular...
Abstract The role and molecular mechanisms of intermittent fasting (IF) in non-alcoholic steatohepatitis (NASH) its transition to hepatocellular carcinoma (HCC) are unknown. Here, we identified that an IF 5:2 regimen (two non-consecutive days food deprivation per week), initiated the active phase mice, prevents/ameliorates NASH fibrosis as well reduces subsequent HCC development without affecting total calorie intake. timing, length number cycles type diet were all critical parameters...
Einleitung Mutiertes Ras (HRAS, NRAS oder KRAS) ist eines der wichtigsten Onkogene bei gastrointestinalen Tumoren und ein prognostisch ungünstiger Faktor. Die Ras-induzierte Tumorigenese verläuft in mehreren Schritten. Aktivierung von onkogenem führt zunächst zur Induktion Seneszenz prämalignen Läsionen. Durch zusätzliche genetische Veränderungen (z.B. Inaktivierung p16INK4A p53) kommt es Entstehung malignen Tumoren.