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Novel eNAMPT Targeting to Modulate Brain and Lung Injury Following TBI Exposure

Award Number: F32HL179757
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 06/05/2026
PERIOD OF PERFORMANCE END DATE: 06/04/2029

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Novel eNAMPT Targeting to Modulate Brain and Lung Injury Following TBI Exposure - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $79,780 )
2026	2026	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Lung Diseases Research	001	1	5/19/2026	NEW	$0
2026	2026	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Lung Diseases Research	000	1	5/19/2026	NEW	$79,780
														Subtotal = $79,780

Grand Total All Awards = $79,780

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Novel eNAMPT Targeting to Modulate Brain and Lung Injury Following TBI Exposure

Award Number: F32HL179757

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 06/05/2026

PERIOD OF PERFORMANCE END DATE: 06/04/2029

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