Sharon Morley, M.D.,Ph.D.

Sharon Morley, M.D.,Ph.D.

Institution: Washington University in St. Louis

Project: COVID-19 infection, NLRP3 inflammasome activation and therapeutic trials to treat ARDS in a mouse model

Grant(s): COVID-19 Respiratory Virus Research Award

Severe acute respiratory virus-coronavirus-2 (SARS-CoV-2), now causing a global pandemic, infects the cells lining the airways and results in fever, cough and shortness of breath. People with severe SARS-CoV-2 lung infections can require hospitalization for supplemental oxygen and mechanical ventilation. Scientists do not understand why some people have such severe lung infections. It may be that immune system “overreaction”—too much inflammation—damages the lungs while trying to repel the virus. We will study a protein complex that may contribute to excess inflammation. We will use cell lines and mice to determine if over-activation of this complex worsens SARS-CoV-2 infection. We will also test two available drugs in mice to reduce inflammation generated by this protein complex, to see if they prevent SARS-CoV-2 infection from causing so much lung damage.

Update:

The kinds of cells and immune proteins that are caused by SARS-CoV2 infection are still not well understood. Using a new mouse model for SARS-CoV2, we are testing the different kinds of cells present in the lungs to find out which cells produce the “alarm” proteins that alert the body’s immune system that there is an infection, and whether reducing or changing the kind of “alarm” proteins can prevent SARS-CoV2 infection from causing too much inflammation. Our goal for this year was to establish which cell type and immune system receptors called inflammasomes were activated in the lungs during SARS-CoV2 pulmonary infection. we are currently studying the NLRP3 inflammasome using a mouse model.

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