Long-term systemic consequences of type 2 skin inflammation on epithelial stem cells
Active Project Grant Awarded Last action
- Award ID
- F31AR083275
- Recipient
-
The Rockefeller University UEI LHGDNJMZ64Y1
- Awarding agency
-
National Insititue of Arthritis and Musculoskeletal and Skin Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $292,424
Award facts
- Assistance listing
- 93.846 Arthritis, Musculoskeletal and Skin Diseases Research
- Completion date 83% complete
- Place of performance
- New York, NY 10065, USA
Award details come from USAspending.gov.
Description
- Abstract
- Modernization has been accompanied by a marked rise in disorders of allergic inflammation. These diseases are frequently borne by epithelial barrier tissues such as the skin, lung, and GUT, which provide essential protection against the inflammatory stresses of the outside world. An emerging hallmark of barrier inflammation is the ability of these tissues to durably adapt to prior experiences, enhancing future responses against a broad range of stressors. The fuchs lab and others have revealed that long-lived epithelial stem cells (epscs), which replenish and repair their tissues throughout life, are key proprietors of these barrier adaptations in the context of type 17 inflammation, generally associated with extracellular pathogen responses. Conversely, how epscs adapt to allergic "type 2" inflammatory exposures remains a poorly understood and urgent unmet health need. To address this critical problem, i seek to use the prevalent epithelial alarmin thymic stromal lymphopoietin (tslp) as a driver to uncover how type 2 skin inflammation impacts the long-term functional responsiveness and epigenetic state of epscs. My preliminary work reveals that transient tslp-driven type 2 skin inflammation endows resident epscs with long-term increased stemness in vitro, and that inflammation- experienced skin retains a concurrently heightened ability to heal wounds in vivo. Surprisingly, i discovered that this lasting hyperresponsiveness extends beyond localized sites of inflammation, as even distal epscs and skin maintain comparably enhanced stemness and wound repair upon resolution, despite having never seen pathologically evident inflammation. With these data in hand, i will define the specific cell-intrinsic mechanisms that distinguish tslp-driven inflammatory memory in both local and systemic contexts, and will interrogate the niche signaling that acts on epscs to establish cellular and tissue-level hyperresponsiveness in each. Lastly, given that my findings thus far could help explain the puzzling frequent interlinking of atopic inflammation in the skin and airway, i will determine whether tslp-driven skin inflammation may have parallel cross-tissue effects, and alter the long-term functionality and epigenetic state of airway epscs. If successful, my findings will reveal important new insights into how allergic inflammation can shape long-term, organism-wide fitness beyond antigen-specific immune sensitization and memory, and add a molecular explanation for long-standing human pathologies that could advance treatment strategies.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $50,114 | |
| Amendment | $48,974 | |
| Amendment | $1,280 | |
| Amendment | $1,280 | |
| Amendment | $47,694 | |
| Amendment | $0 | |
| Amendment | $47,694 | |
| Amendment | $47,694 | |
| Amendment | $0 | |
| Amendment | $47,694 | |
| Original award | $0 |
Show all 11
Quick answers
Who received award F31AR083275?
F31AR083275 was awarded to The Rockefeller University by National Insititue of Arthritis and Musculoskeletal and Skin Diseases (National Institutes of Health) on September 11, 2024.
How much is award F31AR083275 worth?
$292,424 has been obligated on F31AR083275.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award