NIH grant: NAD+ metabolism in pneumonia (1K23HL181207-01A1)

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NIH grant 1K23HL181207-01A1: NAD+ metabolism in pneumonia
Institute: {'code': 'HL', 'abbreviation': 'NHLBI', 'name': 'National Heart Lung and Blood Institute', 'admin_org_id': '12500068', 'admin_funding_url': ''}. PI: Taylor David Coston. Award: $191268.
Start: 2026-08-01T00:00:00.
PROJECT SUMMARY/ABSTRACT
Pneumonia causes more than 3 million deaths annually. Antibiotics are the mainstay of treatment, but
emerging resistance to many antibiotics necessitates identification of alternative therapies. One potential
opportunity involves modulating resident alveolar macrophages (AMs), which maintain lung homeostasis, and
recruited alveolar monocytes (AMos), which replace AMs during pneumonia and can drive sustained
inflammation and tissue injury. Nicotinamide adenine dinucleotide (NAD⁺) is a key regulator of cellular
metabolism, which determines immune cell phenotypes in vitro. NAD+ depletion can occur during acute
inflammation, which disrupts cellular metabolism leading to glycolytic shift and sustained pro-inflammatory
signaling. Dr. Coston’s exciting preliminary data show this process may be of critical importance in pneumonia.
Many therapeutics that modulate NAD⁺ metabolism are already in use and others are being developed.
However, before they can be tested in pneumonia patients, an improved understanding is required regarding
the clinical relevance of NAD⁺-related biomarkers during pneumonia. The goal of this project is to elucidate
clinically relevant metabolites in invasive and noninvasive pulmonary specimens from pneumonia patients and
to characterize NAD+ immunometabolism in cells key to pneumonia host defense.
In Aim 1, Dr. Coston will evaluate an association between bronchoalveolar lavage fluid NAD⁺ metabolites and
patient outcomes in pneumonia. He will test the correlation between invasive and noninvasively obtained
respiratory tract metabolites, facilitating scalable sampling for future studies. In Aim 2, he will characterize
differences in intracellular NAD⁺ concentration between lung and blood myeloid cells collected from pneumonia
patients and define the NAD⁺-related metabolic and transcriptional cellular relationships.
The Career Development Plan for this award proposal is designed to provide training in the prospective study
of clinical pneumonia cohorts as well as the development of a pulmonary biospecimen repository for
translational research. This training will augment Dr. Coston's strong background in clinical epidemiology and
facilitate his goal of developing into an independent clinical and translational physician-scientist elucidating the
metabolic host response to pneumonia. The data generated in this project will lay the foundation for a
multicenter prospective cohort study of patients with pneumonia, leveraging translational collaborations with
metabolic scientists to test the utility of NAD+ therapies to reprogram dysregulated cellular metabolism in
pneumonia patients. Together, these activities will contribute to the development of new therapeutic
approaches to reduce the global burden of pneumonia.

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