Using a combination of in vivo mouse gene targeting studies, in vitro organoid culture approaches, and analyses of human patient samples, we aim to achieve better insight into the role of and interaction between NF-kB signaling, autophagy and ER stress pathways in intestinal homeostasis and pathology.
Hepatic encephalopathy (HE) describes the deterioration of brain function in patients with acute or chronic liver failure. This entity, typified by cognitive, behavioral and motoric deficits, relates to neuronal death, the origin of which is unknown in HE. About 80% of patients suffering from liver cirrhosis are at risk to develop HE, resulting in high morbidity and mortality, reduced quality of life and a high economic burden. Current ...
The endoplasmic reticulum (ER) is responsible for the correct folding of newly formed proteins and their posttranscriptional modification. Unproperly folded proteins accumulate in the ER, consume chaperone molecules and lead to activation of 3 ER stress sensors: ATF6, PERK and IRE1. IRE1 is the most conserve sensor and has 2 catalytic functions: a trans-activating kinase activity and an endonuclease domain resulting in XBP1 activation. XBP1 ...
Hepatic encephalopathy (HE) describes the deterioration of brain function in patients with acute or
chronic liver failure. This entity, typified by cognitive, behavioral and motoric deficits, relates to
neuronal death, the origin of which is unknown in HE. It has been proposed that HE is a gliopathy,
referring to the aberrant neuronal function as a secondary effect to astrocyte dysfunction. HE is
...
Recent evidence suggests that ER stress is activated in conditions of chronic inflammation. The protein A20 is an essential inhibitor of NF-U+F06BB signalling preventing chronic inflammation. We recently generated different A20 tissue-specific knockout mice which all suffer from chronic inflammation in specific disease models. We will use these models to study the complex interplay between chronic inflammation and ER stress, and determine ...
Models of portal hypertension and cirrhosis are used to study the role of ER stress in the development of angiogenesis and fibrosis in the liver and splanchnic circulation. We hypothesize that in PHT and cirrhosis, strategies inhibiting ER stress (by using silencing RNAU+2019s or JIK/Tao3K knockout mice) can decrease inflammation and hypoxia leading to less angiogenesis and fibrosis formation. But that on the other hand, strategies ...
Metabolic reprogramming plays a crucial role in T cell development, differentiation, and acquisition of effector functions. Inadequate metabolic fitness of T cells is a critical factor limiting the efficacy of immunotherapy for cancer therapy, highlighting the need for studies to improve our understanding of T cell metabolic regulation. Growing evidence indicates that metabolism is regulated at highly specialized sites of close appositions ...