About the Lab

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As a part of the University of Pennsylvania’s Pathology Department, the Cherry Lab is interested in the 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 RNA viruses. The laboratory is interested in emerging and globally important arthropod-borne viruses including the three major families that infect humans: the flaviviruses, alphaviruses and bunyaviruses. We are interested in how these viruses are able to hijack cellular factors from insects to humans for their replication using only a small number of proteins. And how these viruses evade immunity is poorly understood. More recently the lab has expanded their studies to the emerging coronaviruses which have more species and cell type specific tropism. The lab explores how the innate immune system, the first line of defense, can recognize and respond to these invaders. Since much of the recognition of these invaders is at the level of nucleic acid recognition, and these are all RNA viruses, we have been exploring the role of RNA binding proteins and the RNA decay machinery in innate antiviral defense against these viruses. We are systematically exploring antiviral innate signaling activities in diverse cell types targeted by these viruses. For example, in the respiratory epithelium in the case of SARS-CoV-2 and neurons in the case of encephalitic arthropod-borne viruses. Moreover, 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. 

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 these studies we found that combining nucleoside biogenesis inhibitors and nucleoside analogs 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. We are screening these drug libraries for additional antiviral activities against a large number of emerging RNA viruses.

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.