Daniel Weiss, M.D., Ph.D.

Daniel Weiss, M.D., Ph.D.

Institution: The University of Vermont State and Agricultural College

Project: Mechanisms of SARS-CoV-2 induced type 2 alveolar epithelial cell pathogenesis

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

The severe acute respiratory syndrome coronavirus-2 (COVID-19) pandemic has prompted an urgent need to better understand the virus at a cellular level so that we can develop new therapeutics. In particular, the role of alveolar type 2 epithelial cells (AT2s) in COVID-19 respiratory failure remains poorly understood. AT2s are critically important for normal lung function. They are responsible for surfactant production and have the ability to turn into other alveolar cell types and participate in repair from injury, including viral injury. Increasing evidence demonstrates that AT2s are a primary lung target for infection with the virus that causes COVID-19, called SARS-CoV-2. However, little is known about the specific mechanisms by which virus infection damages normal AT2 functions and contributes to COVID-19 respiratory failure. We have a novel system of studying human AT2 cells that we will use to address these questions.

Update:

We developed a new model system utilizing SARS-CoV-2 spike protein as a surrogate for virus-cell interactions. We have developed initial data on how spike protein binding to angiotensin-converting enzyme 2 (ACE2) expressed on AT2 cell surfaces might disturb AT2 function, leading to respiratory failure. These continuing studies will provide both novel information as well as open potential new therapeutic avenues.

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