Novel eNAMPT Targeting to Modulate Brain and Lung Injury Following TBI Exposure
NHLBI - National Heart Lung and Blood Institute
About This Grant
PROJECT SUMMARY/ ABSTRACT A major hallmark of traumatic brain injury (TBI), a leading cause of US disability and death, is non-resolving central nervous system (CNS) inflammation that systemically impacts multiple organs including the respiratory system. Approximately 25% of TBI-exposed patients develop acute lung injury and mechanical ventilation exposure contributes to brain injury and cognitive loss via a bi-directional mechanism termed the lung-brain axis. The PI of this F-32 application is a post-doctoral fellow who seeks to extend his training in TBI pathobiology to explore the specific role of eNAMPT (nicotinamide phosphoribosyltransferase) in mediating TBI- mediated inflammation and injury. The PI’s mentor identified NAMPT as a ubiquitously-expressed key metabolic enzyme regulating nicotinamide/NAD metabolism. However, similar to many damage-associated molecular pattern proteins (DAMPs), when eNAMPT is extracellularly secreted/released by injured cells via pyroptotic and non-pyroptotic mechanisms (or TBI exposure), circulating eNAMPT binds to TLR4 to potently initiate or amplify innate immunity-mediated inflammation. Key preliminary data generated by the PI indicates that TBI-exposed rodents, civilians and warfighters exhibit increased plasma eNAMPT levels that tracks with TBI severity and development of acute lung injury, findings highly similar to sepsis and ARDS subjects. eNAMPT is highly druggable and a humanized eNAMPT-neutralizing ALT-100 monoclonal antibody (mAb) is currently being tested in the PUERTA clinical trial in patients with moderate/severe ARDS. Garcia lab publications indicate that ALT- 100 mAb is highly effective in preclinical mouse, rat and porcine models of ARDS and VILI and in a rat shock tube blast model of lung injury. Thus, eNAMPT/TLR4 targeting appears to be a promising therapeutic approach to reducing TBI-induced lung and brain injury. Via two Specific Aims (SAs), the PI will examine eNAMPT/TLR4 signaling as a critical driver for TBI-mediated bidirectional injury (acute lung injury and ventilator-induced brain injury) along the lung-brain axis. SA #1 will expose both Nampt genetically-engineered mice, with very strong protective phenotypes in ARDS/VILI models, and wild type C57Bl6 mice receiving the ALT-100 mAb, to moderate controlled cortical impact (CCI)-induced TBI. SA #1 will detail the CCI-mediated activation of eNAMPT/TLR4 signaling in both brain and lung tissue injuries utilizing histologic, biochemical and genomic approaches. Using Nampt genetically-engineered, CCI-exposed mice. Finally, SA #2 will determine the therapeutic impact of ALT- 100 mAb in wild type C57Bl6 mice exposed to combined TBI and mechanical ventilation-induced brain and lung injuries. Successful completion of these F32 Aims will provide a better understanding of the role of eNAMPT in neuro- and systemic inflammatory signaling following TBI/MV exposure and with the ensuing first-authored publications, position the PI to submit a K-series career development award to further drive his transition to independent scientist.
Grant Summary
Novel eNAMPT Targeting to Modulate Brain and Lung Injury Following TBI Exposure is a NHLBI - National Heart Lung and Blood Institute grant providing up to $80K for university, nonprofit, healthcare org. Applications are due 2029-06-04 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $80K
2029-06-04
- 1Confirm your organization is eligible for Novel eNAMPT Targeting to Modulate Brain and Lung Injury Following TBI Exposure from NHLBI - National Heart Lung and Blood Institute, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NHLBI - National Heart Lung and Blood Institute before the deadline.
Don't want to draft it yourself?
We'll draft the complete application against NHLBI - National Heart Lung and Blood Institute's requirements, run a quality review, and email you a submission-ready PDF plus an editable Word doc within 5 business days. Most orders deliver in 24-48 hours. Flat $399, any grant size.
AI Requirement Analysis
Detailed requirements not yet analyzed
Have the NOFO? Paste it below for AI-powered requirement analysis.
Novel eNAMPT Targeting to Modulate Brain and Lung Injury Following TBI Exposure: Frequently Asked Questions
Who is eligible for the Novel eNAMPT Targeting to Modulate Brain and Lung Injury Following TBI Exposure?
Novel eNAMPT Targeting to Modulate Brain and Lung Injury Following TBI Exposure is offered by NHLBI - National Heart Lung and Blood Institute and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Novel eNAMPT Targeting to Modulate Brain and Lung Injury Following TBI Exposure provide?
Novel eNAMPT Targeting to Modulate Brain and Lung Injury Following TBI Exposure provides up to $80K per award from NHLBI - National Heart Lung and Blood Institute. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Novel eNAMPT Targeting to Modulate Brain and Lung Injury Following TBI Exposure deadline?
Applications for Novel eNAMPT Targeting to Modulate Brain and Lung Injury Following TBI Exposure are due 2029-06-04 (open). Because deadlines can change, verify the date with the funder, NHLBI - National Heart Lung and Blood Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Novel eNAMPT Targeting to Modulate Brain and Lung Injury Following TBI Exposure?
To apply for Novel eNAMPT Targeting to Modulate Brain and Lung Injury Following TBI Exposure, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NHLBI - National Heart Lung and Blood Institute.