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

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:
BLR&D Research Career Scientist Award
BLR
  • 批准号:
    10618284
  • 财政年份:
    2019
  • 资助金额:
    --
  • 项目类别:
BLR&D Research Career Scientist Award
BLR
  • 批准号:
    9763814
  • 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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