Procejt Leader
Prof. Tingting Yan |
|
Department of pharmacology, School of Pharmacy, China Pharmaceutical University Email: Tingting.yan@cpu.edu |
Primary Biliary Cholangitis (PBC) demonstrates a striking female predominance (9:1 ratio) and faces significant therapeutic challenges, with 40% of patients showing inadequate response to first-line ursodeoxycholic acid and the recent withdrawal of FXR agonists due to safety concerns. Although bile acid metabolic pathways are recognized as central to PBC pathology, recent drug development setbacks have provided new directions for mechanistic research. Despite being recognized as central to PBC pathology, the mechanisms underlying bile acid metabolism's role in regulating sexual dimorphism remain unelucidated. This proposal aims to address three fundamental scientific questions: how sexual dimorphism in bile acid metabolism affects cholangiocyte injury-repair thresholds and female susceptibility; what mechanisms govern the cross-talk between sex hormone signaling and bile acid metabolic networks in PBC progression; and whether sex-stratified bile acid characteristics can reveal novel therapeutic targets for precision medicine.
Our integrated approach combines multi-omics analysis of clinical cohorts with genetic engineering animal models to systematically investigate the role of bile acid metabolism sexual dimorphism in PBC pathogenesis. The study will specifically examine how sex-specific bile acid profiles influence cholangiocyte function and immune responses through modulation of nuclear receptor signaling pathways and cellular repair mechanisms, with particular focus on the unresolved mechanisms behind the striking female predominance in PBC incidence.
The expected outcomes will elucidate the underlying pathological mechanisms of sexual differences in PBC and provide the theoretical foundation for developing sex-specific precision treatment strategies. This research has the potential to advance personalized clinical management of PBC and address the critical unmet needs in current therapeutic approaches for this sexually dimorphic autoimmune liver disease, while resolving the paradoxical relationship between bile acid pathways and sexual dimorphism that has remained poorly understood despite its clinical significance.
TEAM
PhD Students: Mengge Dai, Kaiying Li;
Master students: Caimeng Zhuang, Xi Xu
