Mechanisms of Pol II Elongation in Diffuse Midline Glioma

US · IL NIH grant awarded #nih-5R01NS129860-04

Summary

This project investigates the molecular mechanisms by which H3K27M mutant histones dysregulate Pol II transcription in diffuse midline gliomas (DMGs), aiming to identify specific gene regulatory complexes and their roles in tumor initiation and progression.

What they want

The project proposes three specific aims: 1) Establish roles for Pol II elongation regulators in pre-clinical mouse models of DMG and investigate genetic interactions between the elongation machinery and H3K27M; 2) Apply cutting edge next generation sequencing analyses to dissect mechanisms of crosstalk between Pol II regulatory proteins and H3K27M and determine their roles in promoting abnormal gene regulation in DMG; 3) Investigate an unexpected oncogenic role for Elongin/VHL complexes in promoting malignant gene expression patterns and DMG tumor growth.

Deliverables

New insights into how H3K27M oncogenic histones co-opt specific Pol II regulators to promote tumorigenesis
Uncover molecular mechanisms driving aberrant chromatin and gene regulation in DMG and other cancers

Technical requirements

CRISPR screens
Pre-clinical mouse models
Next generation sequencing analyses

Market context

inferred from NAICS

Professional, Scientific & Technical Services

NAICS 541714

US market size: $2.0T
Typical award: $25K – $50M

Typical buyers

All federal civilianDoDStates

Commonly required

8(a)WOSBSDVOSBPE/PMP

Sector-level estimate — full code lookup not yet in catalog.

Mechanisms of Pol II Elongation in Diffuse…

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