Alveolar macrophage “subsets” play an essential role in almost all aspects of lung health and disease. Determining the origin and functions of these subsets is critical to identifying cellular reprogramming targets for patients with ARDS. We have an active research program at Harborview Medical Center and the University of Washington Medical Center-Montlake that enrolls participants with acute hypoxemic respiratory failure and ARDS. In collaboration with the Mikacenic Lab and the Wurfel Lab, we have analyzed samples collected from this cohort and discovered novel alveolar macrophage subsets with unique transcriptional and phenotypic signatures that are associated with clinical outcomes. We are currently analyzing additional biospecimens collected from this cohort to determine where these alveolar macrophage subsets originate and how they function. Our overall goal is to generate knowledge on how alveolar macrophage subsets develop and function so they might be leveraged as a therapeutic target for inflammatory conditions of the lung.
Funding: DoD (PR182284), NIH (K23 HL144916), Parker B. Francis Foundation
Publications:
– The transcriptional and phenotypic characteristics that define alveolar macrophage subsets in acute hypoxemic respiratory failure. Nat Commun. 2023 Nov 17;14(1):7443 (https://pubmed.ncbi.nlm.nih.gov/37978185/)
– Alveolar Macrophage Transcriptional Programs Are Associated with Outcomes in Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2019 Sep 15;200(6):732-741 (https://pubmed.ncbi.nlm.nih.gov/30990758/)
– Cytometry TOF identifies alveolar macrophage subtypes in acute respiratory distress syndrome. JCI Insight. 2018 May 17;3(10) (https://pubmed.ncbi.nlm.nih.gov/29769438/)
– Peripheral and Alveolar Cell Transcriptional Programs Are Distinct in Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2018 Feb 15;197(4):528-532 (https://pubmed.ncbi.nlm.nih.gov/28708019/)
Collaborators:
Carmen Mikacenic (Benaroya Research Institute) (https://www.benaroyaresearch.org/our-research/labs-research/lab/mikacenic-lab)
Mark Wurfel (University of Washington) (https://pulmccsm.uw.edu/people/faculty/mark-m-wurfel)
Sina Gharib (University of Washington) (https://pulmccsm.uw.edu/people/faculty/sina-a-gharib)