Molecular Epidemiology of RVI

Respiratory viral infection remains a major cause of morbidity and mortality in patients with and without a lung transplant.  However, the immune mechanisms that contribute to the severity, repair, and long-term consequences following respiratory viral infection are poorly understood.  Our overall goal is to determine how the host immune response to different viral infections contributes to outcomes in immunosuppressed and non-immunosuppressed individuals. 

In collaboration with the SARI-Prep Investigators (non-lung transplant), we are determining how the host response differs between different types of viral infection (e.g. SARS-CoV-2 vs. influenza vs. RSV).  We are also using molecular measurements and epidemiologic approaches to identify the clinical characteristics and immune signatures associated with post-infectious outcomes. 

In collaboration with the Hachem Lab, Benvenuto Lab, the Fisher Lab, and the Cystic Fibrosis Lung Transplant Consortium, we are enrolling a prospective cohort of lung transplant recipients with respiratory viral infections.  We are analyzing biospecimens from this cohort using proteomic, single-cell, and microbiologic methods to determine whether “immune checkpoint” signatures are associated with development of CLAD following respiratory viral infection.  Our overall goal is to identify ways to risk stratify patients for CLAD following acute events such as infection, and to uncover therapeutic targets that could prevent the onset of CLAD.  

Funding: Cystic Fibrosis Foundation (CFF003753AB322), CDC Foundation (SARI-Prep), Cystic Fibrosis Foundation (CFF003379122)

Publications:

– CXCL10 and Soluble Programmed Death-Ligand 1 during Respiratory Viral Infections Are Associated with Chronic Lung Allograft Dysfunction in Lung Transplant Recipients. Am J Respir Cell Mol Biol. 2022 May;66(5):577-579 (https://pubmed.ncbi.nlm.nih.gov/35486077/)

– Chemokines, soluble PD-L1, and immune cell hyporesponsiveness are distinct features of SARS-CoV-2 critical illness. Am J Physiol Lung Cell Mol Physiol. 2022 Jul 1;323(1):L14-L26 (https://pubmed.ncbi.nlm.nih.gov/35608267/)

– Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study. Crit Care. 2021 Apr 19;25(1):148 (https://pubmed.ncbi.nlm.nih.gov/33874973/)

Collaborators:

Megan Neeley (Duke University, CTOT) (https://medschool.duke.edu/profile/megan-lee-neely)

Scott Palmer (Duke University, CTOT) (https://medicine.duke.edu/profile/scott-michael-palmer)

John Belperio (UCLA, CTOT) (https://profiles.ucla.edu/john.belperio)

Pavan Bhatraju (University of Washington, SARI-Prep) (https://pulmccsm.uw.edu/people/faculty/pavan-bhatraju)

Ramsey Hachem (Washington University in St. Louis) (https://physicians.wustl.edu/people/ramsey-hachem-md/)

Luke Benvenuto (Columbia University) (https://www.vagelos.columbia.edu/profile/luke-j-benvenuto-md)

Carmen Mikacenic (Benaroya Research Institute) (https://www.benaroyaresearch.org/our-research/labs-research/lab/mikacenic-lab)

Cindy Fisher (University of Washington) (https://aid.uw.edu/people/faculty/infectious-diseases/Cynthia-Fisher)

Chris Goss (University of Washington) (https://pulmccsm.uw.edu/people/faculty/christopher-h-goss)

Kathy Ramos (University of Washington) (https://pulmccsm.uw.edu/people/faculty/kathleen-ramos)

Mark Wurfel (University of Washington, SARI-Prep) (https://pulmccsm.uw.edu/people/faculty/mark-m-wurfel)

Laura Evans (University of Washington, SARI-Prep) (https://pulmccsm.uw.edu/people/faculty/laura-evans)