PROJECTS LIST

R37 DK41876, MERIT Award, Gores (PI) 04/01/00 – 03/31/10
NIH/NIDDK
Mechanisms of Liver Cell Injury
Long-Term Objectives and Specific Aims: The overall objective of this proposal is to understand the cellular mechanisms by which bile salts modulate hepatocyte apoptosis in cholestasis. The specific aims are to test the hypothesis that: i) toxic bile acids induce apoptosis by a Fas-dependent process; ii) toxic bile salts increase cell surface Fas by altering cellular trafficking of Fas; and iii) nontoxic hydrophobic bile salts directly signal cell survival pathways by a phosphoinositide 3-kinase-dependent mechanism.

R56 DK59427, Gores (PI) 07/01/07 – 06/30/2011
NIH/NIDDK
Mechanisms of Carcinogenesis in Biliary Epithelia
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 the hypothesis that: 1) IL-6 upregulates Mcl-1 cellular protein levels; 2) Mcl-1 binds TRAIL-mediated apoptosis; and 3) Mcl-1 sustains cholangiocarcinoma cell survival in vivo.

RO1 DK063947 Gores (PI) 08/01/03 – 05/31/08
NIH/NIDDK
Organelle Dysfunction and Apoptosis
Long-Term Objectives and Specific Aims: The overall objective of this proposal is to define the cellular mechanisms causing liver injury by TNF-. The specific aims are to test the hypothesis that: 1) TNF- signals lysosomal permeabilization releasing cathepsin B into the cytosol; 2) release of lysosomal cathepsin B into the cytosol triggers the mitochondrial pathway of apoptosis; and 3) cathepsin B knockout mice are resistant to liver injury and fibrosis following bile duct ligation.