Project Details
Grant Program
Faculty-development competitive research grants program for 2023-2025
Project Description
The goal of this project is to uncover the mechanism(s) of Zeb1-mediated inactivation of p53 in cancer cells and apply this information towards the search of FDA-approved drugs or combination thereof that would selectively target such EMT cells. To reach this goal we would need to address several objectives described below:
Objective 1. To determine whether Zeb1-mediated down-regulation of p53 is a universal mechanism or it is cell type- and p53 mutation status-specific.
Objective 2. To define the molecular mechanism(s) of Zeb1-mediated repression of p53.
Objective 3. To investigate the functional consequences of Zeb1-mediated repression of p53 in respect to drug resistance.
We believe that the accomplishment of this project will generate several important results. First, we expect to decipher the mechanism of Zeb1-mediated repression of p53 in EMT cells, which is important for understanding the basic mechanisms of tumor suppression. Furthermore, results obtained through the course of this project will also have a significance for translational research. In particular, our expected results on the search of new combinations of drugs to effectively eliminate EMT cells may lead to the implementation of new therapeutic schemes to treat solid tumors. We expect that the results of our studies will be disclosed in several publications in respected international journals with high impact factors. Future experiments will require the use of animal models to test the efficacy of the inhibitors of EMT-driven tumor progression and if successful may provide the basis for subsequent patenting.
Objective 1. To determine whether Zeb1-mediated down-regulation of p53 is a universal mechanism or it is cell type- and p53 mutation status-specific.
Objective 2. To define the molecular mechanism(s) of Zeb1-mediated repression of p53.
Objective 3. To investigate the functional consequences of Zeb1-mediated repression of p53 in respect to drug resistance.
We believe that the accomplishment of this project will generate several important results. First, we expect to decipher the mechanism of Zeb1-mediated repression of p53 in EMT cells, which is important for understanding the basic mechanisms of tumor suppression. Furthermore, results obtained through the course of this project will also have a significance for translational research. In particular, our expected results on the search of new combinations of drugs to effectively eliminate EMT cells may lead to the implementation of new therapeutic schemes to treat solid tumors. We expect that the results of our studies will be disclosed in several publications in respected international journals with high impact factors. Future experiments will require the use of animal models to test the efficacy of the inhibitors of EMT-driven tumor progression and if successful may provide the basis for subsequent patenting.
| Status | Active |
|---|---|
| Effective start/end date | 1/1/23 → 12/31/25 |
Keywords
- Epithelial-to-Mesenchymal TransitionT
- p53
- Zeb1
- drug screening
- post-translational modifications
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