Why some LAM cells don’t respond to mTOR-blocking medicines like sirolimus
Cellular determinants of responsiveness to mTOR inhibitors in LAM
This project looks for the cell changes that make lymphangioleiomyomatosis (LAM) stop responding to sirolimus so new treatment targets can be found for LAM patients.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Cincinnati Childrens Hosp Med Ctr NIH-funded |
| Lab location | 1 site (Cincinnati, United States) |
| Project ID | NIH-11267970 on NIH RePORTER |
What this research studies
From my point of view as a person with LAM, researchers are using single-cell RNA sequencing on patient lung samples and laboratory models to find the small group of cells that resist sirolimus. They study LAM lung explants, a sirolimus-resistant LAM cell line, and xenograft models to track active pathways such as YAP-WNT and stemness markers. The team will test whether these pathways keep cells alive independently of mTORC1 and use molecular tools to pinpoint the cellular mechanisms of resistance. The goal is to reveal targets that could lead to new therapies for people whose disease does not respond well to current mTOR inhibitors.
Who could benefit from this research
Good fit: Ideal candidates are people diagnosed with LAM, particularly those whose lung function worsens or stops improving despite sirolimus treatment or who cannot tolerate sirolimus.
Not a fit: People without LAM, and LAM patients who are well controlled on sirolimus and not seeking alternative options, are unlikely to receive direct benefit from this project right now.
Why it matters
Potential benefit: If successful, this work could identify new drug targets or strategies to help people with LAM who do not respond to or cannot stay on sirolimus.
How similar studies have performed: Sirolimus is already known to stabilize LAM for many patients, but resistance or relapse is recognized, and applying single-cell genomics and pathway-focused lab work to find resistance mechanisms is a relatively new but promising strategy.
Where this research is happening
Cincinnati, United States
- Cincinnati Childrens Hosp Med Ctr — Cincinnati, United States (Active)
Researchers
- Principal investigator: Xu, Yan — Cincinnati Childrens Hosp Med Ctr
- Study coordinator: Xu, Yan
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.