How Integrator and PP2A control transcription in human cells
Official title: Control of transcriptional integrity by Integrator and PP2A
Funded at Wistar Institute · NIH-11376134 · Data updated 2026-11-12
A study to understand how a cellular machine called Integrator, together with PP2A, controls when RNA polymerase II pauses and resumes copying genetic information in human cells, and how disease-related PP2A changes affect this process.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Wistar Institute NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project start | June 1, 2026 |
| Project end | March 31, 2031 |
| Funding year | 2026 |
| Award (this year) | $591,549 |
| NIH project number | 1R01GM152664-01A1 |
| Project ID | NIH-11376134 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates are individuals whose cells or neural differentiation models can reflect human transcriptional regulation and disease-related PP2A mutations.
✕Less likely to help
Patients without conditions related to RNAPII pausing or PP2A mutations may not directly benefit from this basic-transcription study.
What this research studies
This project aims to uncover the molecular details of how RNA polymerase II pauses and restarts during gene transcription in mammals, focusing on the Integrator-PP2A module. Researchers will map how Int-PP2A places PP2A at active genes and how it counteracts CDK9 to regulate the RNAPII CTD. They will explore how the INTS3 subunit helps establish paused RNAPII, investigate a potentially critical methylation step on PP2A, and test how disease-associated PP2A mutations affect transcription during neuronal differentiation. The work uses human cells and relevant models to connect basic transcription control with conditions that impact neural development.
Why it matters
Potential benefit: Understanding these mechanisms could reveal new targets to influence gene expression in neurological diseases and other disorders linked to transcriptional misregulation.
How similar studies have gone: Prior work has shown that phosphatases and CDKs coordinate transcription in mammalian cells, supporting the relevance of this regulatory module.
Where this research is happening
-
Wistar Institute
Philadelphia, United States Active
Researchers
- Principal investigator: Gardini, Alessandro — Wistar Institute
- Study coordinator: Gardini, Alessandro
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About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.