Cytoskeletal determinants of pathogenesis of cholestatic liver disease
Public support
Provider
Czech Science Foundation
Programme
Standard projects
Call for proposals
SGA0202600001
Main participants
Ústav molekulární genetiky AV ČR, v. v. i.
Contest type
VS - Public tender
Contract ID
26-20811S
Alternative language
Project name in Czech
Cytoskeletal determinants of pathogenesis of cholestatic liver disease
Annotation in Czech
Cholestasis is a leading cause of liver failure, yet the molecular mechanisms enabling the liver to withstand cholestatic stress remain elusive. Our recent findings reveal that plectin, a cytoskeletal crosslinker, is essential for maintaining bile canaliculi integrity and hepatobiliary transport during injury. In this project, we will define how plectin-controlled cytoskeletal networks remodel the hepatobiliary system to sustain bile flow under stress. We will combine in vivo analyses of two complementary mouse models—liver-specific plectin-deficient mice and newly generated knock-in model carrying patient-derived mutations associated with progressive familial intrahepatic cholestasis (PFIC), a severe pediatric liver disease—with advanced imaging, biomechanics, and functional assays. In parallel, we will validate these findings using CRISPR-engineered human hepatocyte models harboring PFIC-linked mutations. Together, this integrated approach will uncover disease-driving mechanisms and provide a solid foundation for future translational and therapeutic strategies against cholestasis.
Scientific branches
R&D category
ZV - Basic research
OECD FORD - main branch
30219 - Gastroenterology and hepatology
OECD FORD - secondary branch
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OECD FORD - another secondary branch
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CEP - equivalent branches <br>(according to the <a href="http://www.vyzkum.cz/storage/att/E6EF7938F0E854BAE520AC119FB22E8D/Prevodnik_oboru_Frascati.pdf">converter</a>)
FE - Other fields of internal medicine
Solution timeline
Realization period - beginning
Jan 1, 2026
Realization period - end
Dec 31, 2028
Project status
Z - Beginning multi-year project
Latest support payment
—
Data delivery to CEP
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data delivery code
CEP26-GA0-GA-R
Data delivery date
Apr 27, 2026
Finance
Total approved costs
9,864 thou. CZK
Public financial support
9,864 thou. CZK
Other public sources
0 thou. CZK
Non public and foreign sources
0 thou. CZK