A5061166211- Liver physiology and pathology
- Pediatric Hepatobiliary Diseases and Treatments
- Ion Channels and Receptors
- Pancreatic function and diabetes
- Calcium signaling and nucleotide metabolism
- Liver Disease Diagnosis and Treatment
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Pancreatic and Hepatic Oncology Research
- Hearing, Cochlea, Tinnitus, Genetics
- Organ Transplantation Techniques and Outcomes
- Piperaceae Chemical and Biological Studies
- Epigenetics and DNA Methylation
- Drug Transport and Resistance Mechanisms
- Proteoglycans and glycosaminoglycans research
- Signaling Pathways in Disease
- Circadian rhythm and melatonin
- Pancreatitis Pathology and Treatment
- Adenosine and Purinergic Signaling
- Neurobiology and Insect Physiology Research
- Cancer-related molecular mechanisms research
- Phagocytosis and Immune Regulation
- Glycosylation and Glycoproteins Research
- Inflammasome and immune disorders
- Genetic and Kidney Cyst Diseases
- Cell death mechanisms and regulation
Technical University of Munich
2013-2025
Klinikum rechts der Isar
2013-2024
LMU Klinikum
2018
München Klinik
2018
Stanford University
2007-2012
Franklin University
2006
Charité - Universitätsmedizin Berlin
2006
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...
In peripheral nerves, Schwann cells form the myelin sheath that insulates axons and allows rapid propagation of action potentials. Although a number regulators cell development are known, signaling pathways control myelination incompletely understood. this study, we show Gpr126 is essential for other aspects nerve in mammals. A mutation causes severe congenital hypomyelinating neuropathy mice, expression differentiated markers, including Pou3f1, Egr2, protein zero basic protein, reduced....
Homozygote varitint-waddler (Va) mice, expressing a mutant isoform (A419P) of TRPML3 (mucolipin 3), are profoundly deaf and display vestibular pigmentation deficiencies, sterility, perinatal lethality. Here we show that the carrying an A419P mutation represents constitutively active cation channel can also be identified in native hair cells as distinct inwardly rectifying current. We hypothesize constitutive activation occurs result helix-breaking proline substitution transmembrane-spanning...
Ductular reactions (DRs) are observed in virtually all forms of human liver disease; however, the histogenesis and function DRs injury not entirely understood. It is widely believed that contain bipotential progenitor cells (LPCs) serve as an emergency cell pool to regenerate both cholangiocytes hepatocytes may eventually give rise hepatocellular carcinoma (HCC). Here, we used a murine model allows highly efficient specific lineage labeling biliary compartment analyze their potential...
Abstract Notch signaling through the Notch2 receptor is essential for normal biliary tubulogenesis during liver development. However, events downstream of critical this process are less well defined. Furthermore, whether also underlies adult hepatic cell fate decisions largely unknown. By implementing different genetic mouse models, we provide a comprehensive analysis that defines role in control developing and liver. We show cell-specific activation by Notch2IC ( N2IC ) transgene leads to...
Background and Aims Small‐molecule flux in tissue microdomains is essential for organ function, but knowledge of this process scant due to the lack suitable methods. We developed two independent techniques that allow quantification advection (flow) diffusion individual bile canaliculi interlobular ducts intact livers living mice, namely fluorescence loss after photoactivation intravital arbitrary region image correlation spectroscopy. Approach Results The results challenge prevailing...
The transient receptor potential channels TRPML2 and TRPML3 (MCOLN2 MCOLN3) are nonselective cation channels. They widely expressed in mammals. However, little is known about their physiological function(s) activation mechanism(s). can be activated or rather de-inhibited by exposing it first to sodium-free extracellular solution subsequently high sodium. also a variety of small chemical compounds identified throughput screen inhibited low pH. Furthermore, was found that constitutively active...
TRPML3, a member of the transient receptor potential (TRP) family, is an inwardly rectifying, non-selective Ca2+-permeable cation channel that regulated by extracytosolic Na+ and H+ can be activated variety small molecules. The severe auditory vestibular phenotype TRPML3(A419P) varitint-waddler mutation made this protein particularly interesting for inner ear biology. To elucidate physiological role murine we conditionally inactivated Trpml3 in mice. Surprisingly, lack functional TRPML3 did...
The varitint-waddler mutation A419P renders TRPML3 constitutively active, resulting in cationic overload, particularly sustained influx of Ca(2+). is expressed by inner ear sensory hair cells, and we were intrigued the fact that cells are able to cope with expressing TRPML3(A419P) isoform for weeks before they ultimately die. We hypothesized survival linked their ability deal Ca(2+) loads due abundance plasma membrane calcium ATPases (PMCAs). Here, show PMCA2 significantly reduced...
Cellular calcium homeostasis is regulated by hormones and neurotransmitters, resulting in the activation of a variety proteins, particular, channel proteins plasma membrane intracellular compartments. Such channels are, for example, TRP TRPC protein family that are activated various mediators from receptor-stimulated signaling cascades. In Drosophila, two channels, TRPL, involved phototransduction. addition, third Drosophila channel, TRPgamma, has been identified described as an auxiliary...
Significance JNK signaling has been studied intensively in models of liver physiology and disease, but previous studies had focused on young mice. However, it not recognized that plays a fundamental role maintaining homeostasis preventing the formation biliary cysts aging These observations call for caution all long-term pharmacological inhibition strategies targeting pathway. Finally, our results provide evidence molecular link between cell-death mediator RIPK1. The specific overexpression...
Ductular reactions (DRs) are observed in virtually all forms of human liver disease. Nevertheless, the histogenesis and function DRs injury not entirely understood. It is widely believed that contain bipotential progenitor cells (LPCs) serve as an emergency cell pool to regenerate both, cholangiocytes hepatocytes, may eventually give rise hepatocellular carcinoma (HCC). Here we provide a thorough analysis on their potential contribution regeneration carcinogenesis. Using mouse model allows...
Background Chronic cholestatic liver injury is linked to inflammation, the emergence of ductular reactions and fibrosis. While expression CD44, a cellular adhesion molecule, associated with fibrosis in different animal models, it remains unclear if CD44 has functional role processes culminating development hepatic In this study, we investigated chronic Mdr2-/- mice.
Abstract Small-molecule flux in tissue-microdomains is essential for organ function, but knowledge of this process scant due to the lack suitable methods. We developed two independent techniques that allow quantification advection (flow) and diffusion individual bile canaliculi interlobular ducts intact livers living mice, namely Fluorescence Loss After Photoactivation (FLAP) Intravital Arbitrary Region Image Correlation Spectroscopy (IVARICS). The results challenge prevailing...
In response to liver injury or loss of mass, hepatocytes and cholangiocytes proliferate replace the injured tissue. However, in case chronic biliary disease, when hepatocyte cholangiocyte proliferation is impaired, an expansion small putative progenitors observed (oval cell response). Oval cells reside a niche close terminal bile ducts, called canals Hering, are believed give rise both, ducts. Though controversially debated, these were recently reported not only after but even provide...
Notch signaling via the Notch2 receptor is essential for normal biliary tubulogenesis during liver development. However, events downstream of critical this process are less well defined. Furthermore, whether also underlies adult hepatic cell fate decisions largely unknown.
In virtually all forms of liver injury, ductular reactions (DRs) emerge, which comprise cellular (biliary) phenotype at the portal-parenchymal interface. It is widely believed that reactive cells (DRCs) a transit-amplifying progeny adult facultative stem located in outermost terminals biliary tree, canals Hering. Mainly derived from 2D histological and vitro studies, it has been accepted as basic principle repair these DRCs may act bipotential progenitors serve an emergency compartment. They...