Summary
Research focused on understanding the regulation and function of Wip1 phosphatase, its role in tumor cells and the immune system, and its implications in neurodevelopmental disorders, with the goal of identifying therapeutic modulators.
Regulation and Function of WIP1 Phosphatase and its Role in Tumor Cells
US · IL
NIH
grant
awarded
#nih-1ZIABC011197-17
What they want
The research involves determining the high-resolution crystal structure of Wip1, identifying its functional targets, performing high-throughput screens for modulators, conducting molecular dynamics simulations and kinetic studies, using virtual screening for new candidates, and performing biophysical, biochemical, cell-based, and animal model studies. It also includes investigating Wip1's role in the immune system using mouse models and RNAseq, and studying its impact on neurodevelopment using patient-derived organoids.
Deliverables
- Crystal structure of the PPM1D catalytic domain
- Identification of specific modulators (inhibitors and activators) of Wip1 phosphatase activity
- Mechanistic insights into PPM1D catalytic activity
- Characterization of Wip1's role in the immune system and tumor progression
- Characterization of Wip1's role in neurogenesis and brain development
Technical requirements
- High-resolution crystallography
- High-throughput screening (HTS) assays
- Molecular dynamics simulations
- Kinetic studies
- Virtual screening
- Biophysical, biochemical, and cell-based studies
- Animal models (mouse models, Ppm1d floxed mice, tm1c/mrp8cre mice)
- RNAseq analysis
- Omics methods
- Patient-derived unguided neural organoids (UNOs)
