Projects

Mechanisms of liver cell injury

  • Number: R01DK41876
  • Principal investigator: Gregory J. Gores, M.D.
  • Funded by: National Institute of Diabetes and Digestive and Kidney Diseases
  • Duration: Sept. 30, 1992, to March 31, 2015
  • Long-term objectives and specific aims: The overall objective of this proposal is to understand the cellular mechanisms by which free fatty acids modulate hepatocyte lipoapoptosis. The specific aims are to test these hypotheses: 1. Free fatty acids upregulate expression of p53 upregulated modulator of apoptosis (PUMA). 2. Free fatty acids mediate dysregulation of Mcl-1. 3. In animal models of nonalcoholic fatty liver disease, genetic deletion of apoptosis effectors modulates liver injury.

Mechanisms of carcinogenesis in biliary epithelia

  • Number: R01DK59427
  • Principal investigator: Gregory J. Gores, M.D.
  • Funded by: National Institute of Diabetes and Digestive and Kidney Diseases
  • Duration: July 1, 2001, to April 30, 2017
  • Long-term objectives and specific aims: The overall objective of this proposal is to define the cellular mechanisms responsible for the malignant transformation of biliary epithelia. The specific aims are to test these hypotheses: 1. Hedgehog signaling imparts cholangiocarcinoma cells with distinct survival pathways. 2. Cancer-associated fibroblasts promote hedgehog signaling in cholangiocarcinoma cells. 3. Inhibition of hedgehog signaling is therapeutic in a rodent model of cholangiocarcinoma.

Organelle dysfunction and apoptosis in liver epithelia

  • Number: R01DK063947
  • Principal investigator: Gregory J. Gores, M.D.
  • Funded by: National Institute of Diabetes and Digestive and Kidney Diseases
  • Duration: Aug. 1, 2003, to May 31, 2017
  • Long-term objectives and specific aims: The overall objective of this proposal is to define the cellular mechanisms causing liver injury by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The specific aims are to test these hypotheses: 1. PACS-2 mediates lysosomal permeabilization during TRAIL cytotoxicity. 2. cIAP-1 inhibits lysosomal permeabilization by TRAIL. 3. PACS-2 deletion is salutary in cholestatic liver injury.