Signal Transduction GI Cancer / Rozengurt Laboratory
Key investigator
Enrique Rozengurt, DVM, PhD, AGAF, FRC Path (UK)
Funding
NIH P01CA236585 - Role: Project Leader; Project 2 Chemoprevention and mechanisms of obesity-promoted pancreatic adenocarcinoma,05/01/2020 – 04/30/2025
NIH R21CA258125 - (MPI: Rozengurt; Eibl) Interaction between chronic stress and obesity in pancreatic cancer progression. 05/01/2022 – 04/30/2024
NIH R21AI156592 - (MPI: Reed, Rozengurt) Targeting YAP with statins to prevent antibody-mediated transplant rejection, 012/18/2020 – 11/30/2023
VA Merit ReviewI01 BX003801 - (PI) Identification of the growth-promoting PKD/YAP axis as a novel target for the statins in intestinal epithelial cells, 07/01/18-06/30/23.
Roland Hirshberg Endowed Chair in Translational Pancreatic Cancer Research.
Current research projects
KD1 Signaling and Crosstalk Mechanisms in Intestinal Epithelial Cell Regulation
Aims: 1) characterize the role of PKD1 signaling in intestinal epithelial cell proliferation in vivo and in stem cell-derived intestinal organoids, 2) characterize crosstalk mechanisms between PKD1 and β-catenin signaling systems in intestinal epithelial cells, and 3) identify a novel mechanism of PKD1 regulation through PAK-mediated PKD1 phosphorylation at the N-terminal residue Ser203.
The Hippo/YAP/TAZ Pathway in the Regulation of Intestinal, Pancreatic and Endothelial Cell Proliferation
Aims: 1) Characterize the role of the Hippo/YAP/TAZ pathway in the control of proliferation of intestinal and pancreatic epithelial cells, and 2) Identify the signal transduction pathways that mediate the regulation of YAP expression, localization and phosphorylation in these cells.
Chemoprevention of Pancreatic Cancer with Anti-Diabetic Agents
The aim of this project is to characterize the chemo-preventive effects of metformin on the progression of PanINs using the conditional KrasG12D model subjected to standard or a high fat, high calorie diet (HFCD). This animal model system recapitulates the lesions seen in the human disease, namely pancreatic pre-neoplatic lesions followed by their conversion of carcinoma in situ to invasive ductal pancreatic carcinoma.
Future research directions
The future directions are an extension of the current research: Signal transduction mechanisms through protein kinase cascades; elucidation of crosstalk mechanism between Protein kinase D (PKD) and downstream gene-regulatory programs; novel approaches in the therapy and prevention of GI cancers, especially pancreatic cancer.
