A5061515333- Genetic and Kidney Cyst Diseases
- Pediatric Hepatobiliary Diseases and Treatments
- Liver physiology and pathology
- Liver Disease Diagnosis and Treatment
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Endoplasmic Reticulum Stress and Disease
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- Gallbladder and Bile Duct Disorders
- Drug Transport and Resistance Mechanisms
- Renal and related cancers
- Organ Transplantation Techniques and Outcomes
- Genetics and Neurodevelopmental Disorders
- Liver Diseases and Immunity
- Adenosine and Purinergic Signaling
- Biomedical Research and Pathophysiology
- Cancer-related gene regulation
- Cancer Mechanisms and Therapy
Biogipuzkoa Health Research Institute
2020-2024
University of the Basque Country
2020-2024
Donostia International Physics Center
2020
ORFEO-CINQA Research Network
2020
Cholestasis is characterized by intrahepatic accumulation of bile constituents, including acids (BAs), which promote liver damage. The apical sodium-dependent BA transporter (ASBT) plays an important role in reabsorption and signaling ileum, ducts, kidneys. Our aim was to investigate the pharmacokinetics pharmacological activity A3907, oral systemically available ASBT inhibitor experimental mouse models cholestasis. In addition, tolerability, pharmacokinetics, pharmacodynamics A3907 were...
Cholangiocarcinoma (CCA) comprises a heterogeneous group of malignant tumors associated with dismal prognosis. Alterations in post-translational modifications (PTMs), including NEDDylation, result abnormal protein dynamics, cell disturbances and disease. Herein, we investigate the role NEDDylation CCA development progression.Levels functions together response to pevonedistat (NEDDylation inhibitor) or CRISPR/Cas9 against NAE1 were evaluated vitro, vivo and/or patients CCA. The preneoplastic...
Abstract Background & Aims Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive development of multiple biliary cysts. Recently, novel PLD‐causative genes, encoding for endoplasmic reticulum (ER)‐resident proteins involved in protein biogenesis and transport, were identified. We hypothesized that aberrant proteostasis contributes to PLD pathogenesis, representing a potential therapeutic target. Methods ER stress was analysed at transcriptional (qPCR),...
Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive development of multiple fluid-filled biliary cysts. Most PLD-causative genes participate in protein biogenesis and/or transport. Post-translational modifications (PTMs) implicated stability, localization and activity, contributing to human pathobiology; however, their role PLD is unknown. Herein, we aimed unveil the SUMOylation its potential therapeutic targeting.Levels functional effects SUMOylation, along...
Abstract Background Polycystic liver diseases (PLDs) are genetic inherited disorders characterized by the progressive growth of numerous intrahepatic biliary cysts, which main cause morbidity. Previous studies revealed that cystic cholangiocytes endoplasmic reticulum stress and aberrant posttranslational modification (PTM) proteins, in particular hyper‐SUMOylation, promote PLD pathobiology. Protein NEDDylation is a newly PTM modulates plethora biological processes its dysregulation...
Background and Aims Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive development of symptomatic biliary cysts. Current surgical pharmacological approaches ineffective, transplantation represents the only curative option. Ursodeoxycholic acid (UDCA) histone deacetylase 6 inhibitors (HDAC6is) have arisen as promising therapeutic strategies, but with partial benefits. Approach Results Here, we tested an approach based on design, synthesis, validation a family...