Blood vessel cell changes in KRAS-linked brain arteriovenous malformations
Endothelial-to-mesenchymal transition in mutant KRAS-induced brain as a cause of arteriovenous malformations
This research looks at whether a KRAS gene change causes brain blood vessel cells to change identity and lead to arteriovenous malformations in people with bAVM.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Texas Hlth Sci Ctr Houston NIH-funded |
| Lab location | 1 site (Houston, United States) |
| Project ID | NIH-11238031 on NIH RePORTER |
What this research studies
From a patient's perspective, scientists use mice engineered to carry the KRASG12V mutation in brain blood vessel cells and grow endothelial cells in the lab to see if those cells take on mesenchymal features (EndMT) linked to bAVMs. They measure markers such as CD44, KLF4, TGFβ, Notch, MMPs, and α-SMA to track these cell identity changes and study the role of calpain proteases. The team compares the animal and cell findings with existing human bAVM data to connect laboratory results to patients. The overall approach aims to pinpoint molecular steps that could be targeted by future treatments.
Who could benefit from this research
Good fit: Ideal candidates for any related future patient activities would be people diagnosed with sporadic brain arteriovenous malformations who can provide clinical information or tissue samples, especially if testing shows a KRAS mutation.
Not a fit: Patients with inherited syndromic AVMs, non-brain AVMs, or bAVMs driven by other non-KRAS mechanisms may not directly benefit from findings focused on KRAS-driven pathways.
Why it matters
Potential benefit: If successful, this work could reveal drug targets to prevent or reduce brain arteriovenous malformations and lower the risk of intracerebral bleeding.
How similar studies have performed: Genetic studies have already found activating KRAS mutations in many sporadic bAVMs and prior mouse and cell models have reproduced AVM-like features, but pharmacologic treatments targeting this pathway are not yet proven in patients.
Where this research is happening
Houston, United States
- University of Texas Hlth Sci Ctr Houston — Houston, United States (Active)
Researchers
- Principal investigator: Kim, Eunhee — University of Texas Hlth Sci Ctr Houston
- Study coordinator: Kim, Eunhee
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 below.