Jie Sun, PhD
Harrison Distinguished Teaching Professor Jie Sun, PhD, in the UVA Beirne B. Carter Center for Immunology Research and the Department of Medicine’s Division of Infectious Diseases and International Health, has secured two new five-year NIH R01 awards totaling $6.2 million. Dr. Sun’s projects aim to unravel why some people, especially older adults, never fully bounce back after severe respiratory infections such as COVID-19 or influenza and to develop strategies that restore healthy lung function.
The first grant, funded by the National Institute of Allergy and Infectious Diseases, focuses on the lingering lung problems that plague many “long-COVID” patients. Dr. Sun’s team has discovered that an immune alarm signal called interferon-gamma can remain switched on after the virus is gone, prompting a prolonged conversation between lung-resident T cells and macrophages that fuels scarring. Over the next five years, the researchers will pinpoint exactly how interferon-gamma from T cells sparks this chronic inflammation, test whether blocking its partner pathway (STAT1) in macrophages prevents long-term damage, and chart the entire molecular chain in search of drug targets.
The ultimate goal is to lay the groundwork for therapies that can stop, or even reverse, persistent lung injury after COVID-19 or other severe respiratory viral infections, common in the elderly. ~Jie Sun
The second award, from the National Institute on Aging, tackles a different piece of the puzzle: why older lungs heal more slowly after infections. Alveolar macrophages, the lungs’ resident cleanup crew, normally self-renew and calm inflammation, but with age they lose this “stem-like” vitality and adopt a senescent, inflammatory profile. Dr. Sun’s lab has shown that two key proteins act like a molecular seesaw that determines whether these cells repair tissue or exacerbate damage. The new study will decode how that balance is lost during aging, explore the consequences for influenza and COVID-19 recovery, and test an inhaled RNA therapy approach that delivers key proteins to rejuvenate macrophages and speed healing in older adults.
“Together, these complementary projects approach the same public health challenge from different angles to help ensure full recovery after infections,” said Dr. Sun.
By clarifying the immune circuits that derail healing and piloting targeted interventions, Dr. Sun and his collaborators at UVA and the Mayo Clinic aim to pave the way for precision therapies that let patients breathe easier long after the virus has cleared, while training the next generation of scientists in cutting-edge immunology and aging research.