BLR&D Research Career Scientist Award
BLR
基本信息
- 批准号:9912633
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-04-01 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:Alcoholic Liver DiseasesAngiogenic FactorAreaAwardBasic ScienceBile Duct EpitheliumBiliaryCalcitonin Gene-Related PeptideCell AgingCellsCholangiocarcinomaCholestasisChronicClinicalClinical SciencesCollaborationsCyclic AMPDataDevelopmentDiagnosisDiseaseDisease ProgressionDuctal Epithelial CellEducational process of instructingEpithelial CellsFacultyFatty AlcoholsFatty LiverFibrosisFoundationsFundingGastroenterologyGastrointestinal DiseasesGenesGoalsGrantGrant ReviewGrowthHealthHepatic Stellate CellHepatobiliaryHepatologyHeterogeneityHomeostasisHumanIn VitroInflammationInterventionInvestigationJournalsKnowledgeLiver CirrhosisLiver FailureLiver FibrosisLiver diseasesMediatingMedicalMedical StudentsMedical centerMelatoninMentorsMicroRNAsModelingMolecularNatureNeoplastic Cell TransformationNeuropeptidesNeurosecretory SystemsNeurotransmittersPathogenesisPathway interactionsPatientsPharmaceutical PreparationsPharmacologic SubstancePhenotypePlayPopulationPostdoctoral FellowPreventionPrimary biliary cirrhosisProgram DevelopmentProliferatingPublicationsPublishingReactionRegulationResearchResearch PersonnelRodentRodent ModelRoleSamplingScientistSecretinSeminalSensorySerotoninSerumServicesSignal PathwaySignal TransductionSubstance PTherapeutic AgentsTherapeutic InterventionTrainingTreatment EfficacyUnited States National Institutes of HealthVeteransViralafferent nerveautocrinebasebile ductbiliary tractcareercell injurycholangiocytecholestatic liver diseasechronic liver diseaseclinically relevanteditorialgraduate studentin vivoliver injuryliver transplantationmeetingsmemberneuroendocrine phenotypenon-alcoholic fatty liver diseasenonalcoholic steatohepatitisnovelparacrinepeptide Pprimary sclerosing cholangitisproblem drinkerprognostic toolprogramsreceptorrepairedresponsesecretin receptorsenescencestem cellssymposiumtherapeutic developmenttherapy developmenttissue injury
项目摘要
Bile duct epithelial cells (i.e., cholangiocytes) are the target cells in cholangiopathies such as primary biliary
cholangitis (PBC), primary sclerosing cholangitis (PSC), and cholangiocarcinoma (CCA), which are
diseases characterized by the damage, proliferation and neoplastic transformation of cholangiocytes.
These cholestatic liver diseases (characterized by coordinated proliferation/damage of biliary epithelial
cells) along with other cholangiopathies represent a major clinical challenge due to the lack of effective
therapeutic interventions resulting in the need for liver transplantation during end-stage liver disease.
Management of cholangiopathies (including drug- or viral-induced liver injury) represents one of the major
challenges for Veterans Health. Targeting the neuroendocrine factors that respond to cholestasis resulting
from tissue injury may help limit inflammation and fibrosis that occur during hepatobiliary damage. There
is a critical need to understand the neuroendocrine triggers of cholangiocyte growth and their responses
to damage during cholestasis, which will help identify key signaling pathways that represent viable targets
for the development of effective therapeutic agents. Our long-term research goal is to develop an
understanding of the neuroendocrine factors and signaling mechanisms regulating biliary growth during
cholestasis, fatty liver and alcohol-induced liver disease, which will provide a foundation for the discovery
of prevention and new pharmaceutical interventions for cholangiopathies and liver diseases characterized
by hepatic fibrosis. For my current funded VA Merit Award, the central hypothesis is based upon the
postulate that the secretin/secretin receptor (Sct/SR) axis signaling is key for mediating the proliferative
and activated profibrogenic biliary phenotype that contributes to the progression of hepatic steatosis and
fibrosis during the pathogenesis of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis
(NASH). In addition, my research program is funded by multiple collaborative NIH R01 grants that explore
various aspects of the regulation of biliary growth and hepatic fibrosis by neuroendocrine factors such as
secretin, melatonin, serotonin and miRNAs in models of cholestasis, NAFLD, and alcohol-induce liver
disease. My collaborative effort with multiple VA investigators has been high productive and has resulted
in many publications in high impact journals. The exploration of the neuroendocrine features of
cholangiocytes will provide new avenues for the development of therapeutic interventions for these
diseases. Our contribution is significant since this is a critical step to provide translational knowledge for
the development of therapies for cholangiopathies. These findings will also have broader implications for
other hepatic diseases characterized by hepatic fibrosis.
胆管上皮细胞(即胆管细胞)是原发性胆道等胆管病变的靶细胞
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Gianfranco D Alpini其他文献
Gianfranco D Alpini的其他文献
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{{ truncateString('Gianfranco D Alpini', 18)}}的其他基金
Regulation of Ductular Reaction by Substance P during Alcohol-induced Liver Injury
P物质对酒精性肝损伤过程中小管反应的调节
- 批准号:
10592570 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Role of Sensory Innervation in High Fat Diet-Induced Hepatotoxicity
感觉神经支配在高脂肪饮食引起的肝毒性中的作用
- 批准号:
10467095 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Role of Sensory Innervation in High Fat Diet-Induced Hepatotoxicity
感觉神经支配在高脂肪饮食引起的肝毒性中的作用
- 批准号:
10596643 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Alcohol-induced hepatotoxicity - implications of secretin/secretin receptor axis
酒精引起的肝毒性 - 促胰液素/促胰液素受体轴的影响
- 批准号:
10252062 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Alcohol-induced hepatotoxicity - implications of secretin/secretin receptor axis
酒精引起的肝毒性 - 促胰液素/促胰液素受体轴的影响
- 批准号:
10457005 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Alcohol-induced hepatotoxicity - implications of secretin/secretin receptor axis
酒精引起的肝毒性 - 促胰液素/促胰液素受体轴的影响
- 批准号:
10676118 - 财政年份:2020
- 资助金额:
-- - 项目类别:
ShEEP Request for Leica Laser Capture Microdissection System (LMD7)
ShEEP 请求徕卡激光捕获显微切割系统 (LMD7)
- 批准号:
9908938 - 财政年份:2019
- 资助金额:
-- - 项目类别:
The Role of Stem Cell Derived Microvesicles in Cholestatic Liver Injury
干细胞衍生的微泡在胆汁淤积性肝损伤中的作用
- 批准号:
9930828 - 财政年份:2019
- 资助金额:
-- - 项目类别:
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