Determining the molecular epidemiology of critical illness syndromes is imperative to understanding disease pathophysiology, identifying treatment targets, and predicting which patient populations are most responsive to therapies. In collaboration with the Wurfel Lab, the Fessler Lab, the Mikacenic Lab, investigators at the UW Center for Lung Biology, and the UW-SCORE Group, we have identified novel genetic pathways, soluble proteins, and lipid mediators that are associated with outcomes in patients with critical illness syndromes such as ARDS, sepsis, and trauma. We have an active research program at Harborview Medical Center that enrolls patients with acute respiratory failure supported on invasive mechanical ventilation. We are currently analyzing respiratory and blood biospecimens from this cohort to determine cellular and molecular signatures that contribute risk to outcomes in patients with pneumonia and ARDS. Our overall goal is to determine how the alveolar and systemic immune response to infection and injury might be modified to improve outcomes for patients.
Funding: NIH (K23 HL144916)
Publications:
– Association of Trauma Molecular Endotypes With Differential Response to Transfusion Resuscitation Strategies. JAMA Surg. 2023 Jul 1;158(7):728-736 (https://pubmed.ncbi.nlm.nih.gov/37099286/)
– 25-Hydroxycholesterol exacerbates vascular leak during acute lung injury. JCI Insight. 2023 Apr 10;8(7) (https://pubmed.ncbi.nlm.nih.gov/36821369/)
– Alveolar Biomarker Profiles in Subphenotypes of the Acute Respiratory Distress Syndrome. Crit Care Med. 2023 Jan 1;51(1):e13-e18 (https://pubmed.ncbi.nlm.nih.gov/36519995/)
– Alveolar CCN1 is associated with mechanical stretch and acute respiratory distress syndrome severity. Am J Physiol Lung Cell Mol Physiol. 2020 Nov 1;319(5):L825-L832 (https://pubmed.ncbi.nlm.nih.gov/32936024/)
– Alveolar MMP28 is associated with clinical outcomes and measures of lung injury in acute respiratory distress syndrome. Crit Care. 2020 Apr 8;24(1):141 (https://pubmed.ncbi.nlm.nih.gov/32268921/)
– Genetic Variation in MAP3K1 Associates with Ventilator-Free Days in Acute Respiratory Distress Syndrome. Am J Respir Cell Mol Biol. 2018 Jan;58(1):117-125 (https://pubmed.ncbi.nlm.nih.gov/28858533/)
Collaborators:
Mark Wurfel (University of Washington) (https://pulmccsm.uw.edu/people/faculty/mark-m-wurfel)
Mike Fessler (NIEHS) (https://irp.nih.gov/pi/michael-fessler)
Carmen Mikacenic (Benaroya Research Institute) (https://www.benaroyaresearch.org/our-research/labs-research/lab/mikacenic-lab)
Pavan Bhatraju (University of Washington) (https://pulmccsm.uw.edu/people/faculty/pavan-bhatraju)
UW Sepsis Center of Research Excellence (https://score.uw.edu/)
UW Center for Lung Biology (https://pulmccsm.uw.edu/research/clb)