Role of stress granule inhibition in SARS-CoV-2 immunopathogenesis

The overall objective of this project is to advance our understanding of the molecular mechanisms driving lung immunopathology in severe COVID-19, a disease that has profoundly impacted respiratory health worldwide. COVID-19 primarily affects the lungs, with severe patients exhibiting a plethora of clinical respiratory symptoms that culminate acute respiratory distress syndrome (ARDS) and respiratory failure. While initial symptoms result from the direct effects of SARS-CoV-2 infection, severe disease progression is primarily driven by innate immune dysregulation, particularly through excessive pro-inflammatory cytokine production, or “cytokine storm.” Consequently, a major therapeutic strategy in severe cases is to target innate immunity instead of the virus, aiming to modulate the response to improve disease outcomes. However, our incomplete understanding of the molecular mechanisms underlying this immune dysregulation hinders the development of effective treatments. By investigating these mechanisms, our research aims to support the development of new immunomodulatory therapies. With the potential to reduce acute lung injury in severe COVID-19 patients, this work directly aligns with the American Lung Association’s mission to save lives by improving lung health and preventing lung disease.