An interdisciplinary team of Northwestern Medicine investigators led by Karen Ridge, PhD, professor of Medicine in the Division of Pulmonary and Critical Care and of Cell and Developmental Biology, has been awarded a $14 million grant from the National Institute of Health’s National Heart, Lung, and Blood Institute to investigate the mechanisms that promote lung tissue repair in patients with severe viral pneumonia.
The multi-collaborative P01 research program is divided into four sub-projects and three research cores led by several Feinberg investigators including Ridge; Navdeep Chandel, PhD, the David W. Cugell, MD, Professor of Medicine in the Division of Pulmonary and Critical Care and professor of Biochemistry and Molecular Genetics; Scott Budinger, MD, the Ernest S. Bazley Professor of Airway Diseases and chief of Pulmonary and Critical Care in the Department of Medicine; Benjamin Singer, ’07 MD, 10 GME, the Lawrence Hicks Professor of Pulmonary Medicine; Jacob Sznajder, MD, the Ernest S. Bazley Professor of Asthma and Related Disorders; Richard Wunderink, MD, professor of Medicine in the Division of Pulmonary and Critical Care; and Alexander Misharin, MD, PhD, assistant professor of Medicine in the Division of Pulmonary and Critical Care.
In patients with severe viral pneumonia caused by the influenza A virus or SARS-CoV-2 (the virus that causes COVID-19), dysregulated immune responses drive persistent inflammation and development of the early phases of acute respiratory distress syndrome (ARDS), which occurs when the lower respiratory tract becomes damaged due to fluid buildup in the lungs’ air sacs, depriving organs of oxygen.
Despite advances in supportive care, no specific therapies currently exist for patients with ARDS. Unfortunately, most patients will succumb to persistent respiratory failure and multi-organ dysfunction soon after initial infection.
For their project, Ridge and fellow Feinberg investigators plan to identify the immunologic and cellular mechanisms that regulate these immune processes to resolve inflammation and ultimately promote lung tissue repair.
“Our findings will shed light on how inflammation could be resolved and lung repair accelerated in viral pneumonia in order to mitigate the persistent respiratory failure and multi-organ dysfunction currently seen in ARDS. Ultimately, this will lead to better treatments for patients,” Ridge said.
Co-investigators include Deborah Winter, PhD, assistant professor of Medicine in the Division of Rheumatology; Bria Coates, MD, ’08, ’11 GME, assistant professor of Pediatrics in the Division of Critical Care; Curt Horvath, ’92 PhD, professor of Medicine in the Division of Hematology and Oncology and of Microbiology-Immunology; Laura Dada, PhD, research associate professor of Medicine in the Division of Pulmonary and Critical Care; Susanne Herold, MD, PhD, adjunct associate professor of Medicine in the Division of Pulmonary and Critical Care; SeungHye Han, MD, MPH, assistant professor of Medicine in the Division of Pulmonary and Critical Care; and Hiam Abdala-Valencia, PhD, associate professor of Medicine in the Division of Pulmonary and Critical Care.
The project will also utilize resources available through Northwestern’s Successful Clinical Response In Pneumonia Therapy (SCRIPT) Systems Biology Center, led by Wunderink.
“This highly integrated project brings together scientists with a broad spectrum of expertise to determine how multiple, converging immune processes can modify cellular responses in the lung to promote resolution of inflammation and healthy repair of damaged lung tissue after viral pneumonia,” Ridge said.
Chandel, Budinger, Horvath, Misharin and Abdala-Valencia are also members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.