Research

The lab's research program aims to understand the mechanisms of disease pathogenesis associated with respiratory viral infections and to discover new therapeutic targets to reduce the respiratory morbidity caused by different respiratory viruses. One of the goals of our research program is to uncover how respiratory viruses trigger the death of neutrophils and macrophages, specialized innate immune cells and the role of innate cell death on disease pathogenesis. We have previously investigated the signaling pathways activated by respiratory syncytial virus (RSV) to induce NETosis in human neutrophils. NETosis is a mode of neutrophil death that leads to the release of neutrophil extracellular traps (NETs), which can act as antimicrobial threads but can also be detrimental to the host. More recently, we have been interested on the effects of RSV infection in macrophages, including the mechanisms underlying cytokine release by infected macrophages and the mechanisms of disease pathogenesis induced by RSV-triggered alveolar macrophage necroptosis. Necroptosis is a proinflammatory cell death that culminates with the release of intracellular contents, which may act as damage-associated molecular patterns (DAMPs), stimulating immune cells. Our recent data have demonstrated that autocrine TNF-mediated alveolar macrophage necroptosis drives disease pathogenesis during RSV infection. We also show that the activation of necroptosis proteins (RIPK1, RIPK3 and MLKL) is detrimental to virus clearance. Our long-term goal is to expand our studies to understand the mechanisms underlying disease pathophysiology during different respiratory viral infections, including RSV, rhinovirus, influenza and SARS-CoV-2 and to identify therapeutic targets to reduce respiratory morbidity caused by these infections.