The Kenneth Bradley laboratory in the UCLA Department of Microbiology, Immunology & Molecular Genetics is interested in understanding how pathogens interact with their hosts to advance disease pathology. Specifically, the lab is working to identify host genes that are essential for bacterial toxins to exert their effects. Dr. Bradley has previously collaborated with researchers in the Department of Chemistry & Biochemistry to develop a series of novel small molecule inhibitors of endosomal trafficking. The inhibitors may be used to disrupt the cellular entry of bacterial toxins and viruses that require trafficking to acidified endosomes. Such molecules, as well as continued exploration of antimicrobial and antiviral pathways in the Bradley lab, are promising technologies for application to COVID-19 treatment and prevention.
The endocytic pathway is a crucial host cell process consisting of distinct membrane compartments, which internalize molecules from the cellular membrane and recycle them back to the surface or target them for degradation. Coronaviruses, including SARS-CoV-2, rely on the fusion of their viral envelope with the host cell membrane to deliver their nucleocapsid into the host via endocytosis. Small molecule inhibitors that disrupt the binding, entry, and trafficking of bacterial toxins or viruses could be developed as novel therapeutics for the prevention and treatment of such infectious diseases. The class of inhibitors discovered by the Bradley laboratory are powerful tools for the study of SARS-CoV-2 membrane trafficking, and set a foundation for the therapeutic development of host-targeted compounds to treat coronavirus infections.
Link to Faculty website: https://bioscience.ucla.edu/faculty/kenneth-bradley-0
Link to relevant cases:
1) 2013-466 https://techtransfer.universityofcalifornia.edu/NCD/23631.html
2) Selective inhibitor of endosomal trafficking pathways exploited by multiple toxins and viruses. Proc Natl Acad Sci U S. A. (2013)