About the Lab
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As a part of the University of Pennsylvania’s Pathology Department, the Cherry Lab is interested in rhe interface between viruses and hosts. The Lab uses chemical and genetic screening technologies to perform a wide array of cell-based screens in human and insect cells studying emerging viruses with a historical focus on arthropod-borne viruses such as chikungunya and zika virus. And more recently expanded their studies to the emerging coronaviruses. Innate immunity is the first line of defense against viruses and much of the recognition of these invaders is at the level of nucleic acid recognition. Arthropod-borne human viruses are RNA viruses and we are examining the role of RNA binding proteins and the RNA decay machinery in innate antiviral defense against these viruses in human cells. we are also discovering how specific and specialized cell types respond to infection in order to boost antiviral activities. Coronaviruses are respiratory epithelial infections and have identified STING agonists as potent antivirals in this tissue. Some arboviruses are encephalitic, targeting neurons, and we have discovered that interferons cannot protect neurons from infection while other innate pathways can. Thus, we are systematically exploring antiviral innate signaling activities in diverse cell types targeted by viruses. Since arthropod-borne viruses infect the vector insect enterically, we use Drosophila to model these intestinal infections to explore the role of microbiota and innate defenses in the gut in the response to enteric arboviral infections. Projects include understanding how dysbiosis impacts susceptibility and discovering the bacterial products that impact infection. The laboratory has many projects exploring diverse areas of viral-host interactions and innate immunity.
We have also performed large scale screens for antiviral small molecules and have found many new antivirals with activity against SARS-CoV-2. In particular, we are focusing on nucleoside analogs, which are the largest class of known antivirals. We are exploring the mechanism of action of these drugs and how we may combine drugs to increase potency and reduce resistance. Through theses studies we found that combining nucleoside biogenesis inhibitors and nucleoside analogs can can synergistically block SARS-CoV-2 infection in vitro and in vivo. Future studies are aimed at understanding these interactions to improve antiviral development in SARS-CoB-2 and other viral infections.
In addition, the Cherry lab has extended their studies to precision medicine and oncology. In collaborations across UPENN including the high-throughput screening core, oncologists and pathologists the lab has developed a pipeline to test patient tumor cells for sensitivities to chemotherapeutics in an effort to personalize treatments. Work in acute myelogenous leukemia has demonstrated clear differences in patient responses and has uncovered new dependencies that will be translated into new treatment strategies in the future.