Research Project: The Role of ZFYVE21 in COVID-19 Respiratory Complications
COVID-19 Respiratory Virus Research Award
basic biologic mechanisms
COVID-19 is caused by a novel coronavirus, SARS-CoV-2. This virus can cause respiratory failure by infecting different cell types within the lung including blood vessels. In severe COVID-19, infected blood vessels in the lung show changes including inflammation, blood clots and altered permeability, resulting in fluid leakage into lung tissues. Endothelial cells (ECs) are cells that form the inner lining of blood vessels and are targeted for infection by SARS-CoV-2. We will explore the role of a set of immune proteins called complement in triggering gene changes in ECs to promote the blood vessel changes of COVID-19. We will test COVID-19 specimens and use newly developed humanized models to increase the likelihood that our work will yield clinically relevant findings. It is our hope that our studies may inform new therapies to improve survival of COVID-19 patients.
We identified a molecule called ZFYVE21 that may be implicated in the pathologic blood vessel changes occurring during SARS-CoV-2 infection, including blood clots and heart attacks. ZFYVE21 is expressed in endothelial cells, the cells that line blood vessels, and we found that this molecule may regulate COVID-19-related vascular pathologies in endothelial cells. In the upcoming funding period, we are exploring new ways to block the actions of ZFYVE21 with drugs to inhibit these COVID-19-related vascular changes.