Human Pluripotent Stem Cell, Organoids and Infectious Diseases
hPSC-derived cells/organoids provide a platform to systematically evaluate the tropism and cellular response upon viral infection, which can be adapted to screen for anti-viral drugs. Using hPSC-derived forebrain organoids, we identified hippeastrine as a compound that inhibits ZIKV infection. We found that germ cells act as a reservoir for long-term ZIKV propagation and trophectorderm plays a key route in mother-to-fetus ZIKV transmission.
In response to the COVID-19 pandemic, I led a large consortium team to apply hPSC-derived cells/organoids to study SARS-CoV-2 tropism, host response, immune cell-mediated host damage, and antiviral drug screening. We performed the first hPSC-derived lung and colonic organoid-based chemical screen and identified several anti-SARS-CoV-2 drugs. Next, we reported a host-specific response to SARS-CoV-2 infection, including cell apoptosis in lung organoids, ferroptosis in cardiac pacemaker cells and pancreatic beta cell transdifferentiation. In addition, we reported an immune-cardiac platform to model the impact of immune cell-mediated heart damage and identified a JAK inhibitor, which protects host cells from immune cell-mediated damage. At the same time, FDA approved the Emergency Use Authorization of a JAK inhibitor on COVID-19 patients.
Representative confocal image of SARS-N+ cells in ciliated-like cells of hPSC-derived airway organoids.
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