Genetic and mechanistic studies of viral-host interactions.
virus, genomics, RNAi, genetics, Drosophila, innate, immunity.
Description of Research
Research in the Cherry lab is aimed at identifying cellular factors that regulate viral pathogenesis, including factors hijacked by viruses for replication and innate anti-viral mechanisms used by the host to combat the invader. We study a number of arthropod-borne RNA viruses, including flaviviruses such as West Nile virus, dengue virus and the newly emerging Zika virus. We are also studying the alphaviruses including Sindbis and Chikungunya virus as well as the bunyaviruses Rift Valley Fever virus and La Crosse virus. These are the three major families of viruses that are important human pathogens transmitted by mosquitoes to humans.
To identify cellular factors that play important roles in infection we are taking a genetic approach and screening for factors that impact viral replication. We model the vector biology using the genetically tractable model organism Drosophila. This allows us to use a wide-variety of techniques including both high-throughput RNA interference screens in cell culture, and forward genetic screens in animals to identify genes that impact the viral life cycle. We also use human cell culture models to study the infection of mammals performing cell-based screens and mechanistic studies. Combining forward genetics and functional genomics comparing and contrasting between viruses and hosts allows us to use these unbiased and global methodologies to identify many important and novel host factors that modulate virus-host interactions. Through these studies we have discovered a large number of new factors and pathways involved from new pattern recognition receptors and nucleic acid sensing to previously unknown factors required for viral entry. In addition, our recent studies have uncovered new facets of intestinal immunity demonstrating a role for the microbiota in antiviral defense.
Interested students can perform a wide array of cell-based screens in either insect or human cells using emerging arboviruses including chikungunya and zika virus. In addition, in Drosophila, we have projects on intestinal infection where we are dissecting the role of the microbiota in protection from enteric arboviral infections. We have projects understanding how dysbiosis impacts susceptibility and to discover the bacterial products that impact infection. Furthermore, we have projects in human cells to dissect the mechanisms involved in viral RNA recognition and RNA decay as well as to study the mechanisms by which nutrient signaling and autophagy impact viral infection. Depending on the interests of the student, there are many additional possible projects in the areas of viral-host interactions and innate immunity. Students are encouraged to contact Dr. Cherry directly.
Jerome Molleston- CAMB M.D./Ph.D. Student
Frances Taschuk- CAMB Ph.D. Student
Christine Sansone- Postdoctoral Fellow
Brent Hackett- Postdoctoral Fellow
Sneh Harsh- Postdoctoral Fellow
Holly Ramage- Research Assistant Professor
Beth Gold- Research Technician
Keiko Rausch- Research Technician
Nathan Weinbren- Research Technician
Nicole Phan- Undergraduate Researcher
Brennan Lee- Undergraduate Researcher
Emily Hancin- Undergraduate Researcher
Tiffany Huang- Undergraduate Researcher
Sansone, C., Cohen, J., Yasunaga, A., Xu, J., Osborn, G., Subramanian, H., Gold, B., Buchon, N. and Cherry, S. : Microbiota-dependent priming of antiviral intestinal immunity in Drosophila. Cell Host Microbe 18(5): 571-81, Nov 2015.
Beiting, D.P., Hidano, S. Fang, Q. Baggs, J.E., Geskes, J.M., Wherry, J.E., Hunter, C.A., Roos, D.S., and Cherry, S. : A Genomic Screen Identifies the Orphan Nuclear Receptor TLX as an Enhancer of STAT1-mediated Transcription and Immunity to Toxoplasma gondii. PLoS Biology 13(7): e1002200, 2015 Notes: Synopsis in PLoS Biology.
Hopkins, K.C., Tartell, M.A., Herrmann, C., Hackett, B.A., Taschuk, F., Panda, D., Menghani, S., Sabin, L.R., Cherry, S. : Virus-induced translational arrest through 4EBP1/2-dependent decay of 5'TOP mRNAs restricts viral infection. Proc. Natl. Acad. Sci. USA 112(22): E2920-9, Jun 2015.
Hackett, B.A., Yasunaga, A., Panda, D., Tartell, M., Hopkins, K., Hensley, S.E., and Cherry S: RNASEK is required for internalization of diverse acid-dependent viruses. Proc. Natl. Acad. Sci. USA Jun 2015.
Moy, R.H, Cole, B.S., Yasunaga, A., Gold, B., Shankarling, G., Varble, A. Molleston, J., tenOever, B.R., Lynch, K.W. and Cherry S. : Stem loop recognition by DDX17 facilitates miRNA processing and antiviral defense. Cell 178(4): 764-77, Aug 2014.
Panda, D., Pascual-Garcia, P., Dunagin, D., Tudor, M., Hopkins, K.C., Xu, J., Gold, B., Raj, A., Capelson, M. and Cherry, S. : Nup98 promotes antiviral gene expression to restrict RNA virus infection in Drosophila. Proc. Natl. Acad. Sci. USA 111(37): E3890-9, 2014.
Moy, R.H., Gold, B., Molleston, J.M., Schad, V., Langer, K., Salzano, M-V., Yagi, Y., Stanger, B.Z., Soldan, S.S., and Cherry, S. : Restriction of Rift Valley fever virus infection by autophagy is conserved from flies to mammals. Immunity 40(1): 51-65, Jan 2014.
Yasunaga, A., Hanna, S.L., Li, J., Cho, H., Rose. P.P., Spiridigliozzi, A. Gold, B., Diamond, M.S. and Cherry, S. : Genome-wide RNAi screen identifies broadly-acting anti-arboviral host factors. PLoS Pathogens 10(2): e1003914, Feb 2014.
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Last updated: 02/10/2016
The Trustees of the University of Pennsylvania