Leukemia inhibitory factor-dependent modulation of lung endothelial cells during pneumonia
Active Project Grant Awarded Last action
- Award ID
- F31HL178206
- Recipient
-
University Of Massachusetts Medical School UEI MQE2JHHJW9Q8
- Awarding agency
-
National Heart Lung and Blood Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $76,306
Award facts
- Assistance listing
- 93.837 Cardiovascular Diseases Research
- Completion date 0% complete
- Originally
- Place of performance
- Worcester, MA 01655, USA
Award details come from USAspending.gov.
Description
- Abstract
- Pneumonia persists as a leading cause of death, demanding a better understanding of host immune factors controlling responses to respiratory infection. The loss of alveolar-capillary barrier integrity during pneumonia can lead to pathogen dissemination and an influx of vascular fluid into the airspaces, resulting in edema and impaired gas exchange. Thus, the resilience of this barrier is vital for limiting injury. We have identified a cytokine, leukemia inhibitory factor (LIF) as a critical driver of lung tissue protection during bacterial pneumonia, such that pharmacological or genetic interruption of LIF signaling exaggerates pneumonia-induced injury. Yet, the targets and mechanisms of LIF-mediated protection constitute a major knowledge GAP. While our previous results indicate the expression of LIF-receptor (LIFR) in various lung cell populations, endothelial cells appear to be the most prominent source. Both STAT3 and YAP/TAZ (HIPPO) signaling have been implicated downstream of LIFR engagement, but whether these factors coordinate LIF activity in endothelial or other lung cell types is unknown. Our published and preliminary results indicate that LIF-LIFR signaling influences both the STAT3 and YAP/TAZ pathways in lung cells, including the endothelium, and their established roles in cell survival suggest that both STAT3 and YAP/TAZ are mechanistically linked to the protective effects of LIF. Yet, neither the targets nor signals that confer LIF-driven protection during pneumonia are fully understood. Based on these findings, we propose the central hypothesis that LIF-dependent modulation of STAT3 and HIPPO signaling mediates lung endothelial integrity, limiting pneumonia-induced injury, to be tested across two specific aims addressing whether: 1) LIFR expression in lung endothelial cells is a critical determinant of tissue homeostasis during pneumonia, and 2) LIF signaling maintains endothelial cell homeostasis by modulating STAT3 and YAP/HIPPO activity. An improved understanding of these pathways and others controlling pneumonia outcomes has important clinical implications for patients with or at risk for acute lower respiratory infections.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $38,153 | |
| Amendment | $0 | |
| Original award | $38,153 |
Quick answers
Who received award F31HL178206?
F31HL178206 was awarded to University Of Massachusetts Medical School by National Heart Lung and Blood Institute (National Institutes of Health) on December 1, 2026.
How much is award F31HL178206 worth?
$76,306 has been obligated on F31HL178206.
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