Specialty Division

Cancer and Immunobiology

Research Expertise

Research Interests:
Genetic and mechanistic studies of viral-host interactions

Key Words:
Emerging virus, coronavirus, arbovirus, genomics, antivirals, genetics, Drosophila, innate, immunity

Description of Research:
The Cherry Lab is interested in genetic and mechanistic studies of viral-host interactions. The Lab uses chemical and genetic screening technologies to explore the interface between viruses and hosts. The laboratory performs 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. 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. Since these viruses can infect diverse tissues we are also exploring antiviral innate signaling activities in distinct cell types including neurons, endothelial cells, and myeloid lineages. We have demonstrated cell-type specific immune pathways. Moreover, as these arthropod-borne viruses infect the vector insect enterically, we use Drosophila to model these intestinal infections to explore the role of the 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 recent coronavirus pandemic has led us to use our screening technologies to identify drugs that have antiviral activity as well as the role of innate pathways in controlling infection of SARS-CoV-2 in respiratory cells. The laboratory has many projects exploring diverse areas of viral-host interactions and innate immunity.
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.

Rotation Projects:
Interested students can work on diverse aspects of viral-host interactions of emerging viruses from arboviruses to coronaviruses. They can involve the study of factors that facilitate infection such as entry pathways or the study of innate immune mechanisms at play.

Lab Personnel:
Benjamin Gabriel	Senior Research Investigator		Iulia Tapescu	Graduate Student - BMB Grad Student
Kasirajan Ayyanathan	Senior Research Investigator		Rachel Braun	Graduate Student - BMB Grad Student
Marie Arvidson	Research Specialist A		Tamanna Srivastava	Graduate Student - BMB Grad Student
Alex Huber	Research Specialist B		Jorge Acuña	Graduate Student - CAMB Grad Student
Jesse Hulahan	Research Specialist C		Kaeri Martinez	Graduate Student - CAMB Grad Student
Jesse Miller	Research Specialist C		Mark Dittmar	Graduate Student - CAMB Grad Student
Beth Gordesky Gold	Research Specialist D		Trevor Griesman	Graduate Student - CAMB Grad Student
Swechha Mainali Pokharel	Research Specialist D		Ashley Abraham	Undergraduate
Guangda Shi	Postdoctoral Researcher		Lara Hairapetian	Undergraduate
Jaeseung Lee	Postdoctoral Researcher		Oleksandr Zginnyk	Undergraduate
Max Ferretti	Postdoctoral Researcher
Priyanka Bhakt	Postdoctoral Researcher
Steven Miller	Postdoctoral Researcher
Zienab Etwebi	Postdoctoral Researcher

Itmat Expertise: 
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.

Graduate Groups

Biochemistry and Molecular Biophysics
Cell and Molecular Biology
Genomics and Computational Biology
Immunology
Pharmacology

Education

BS (Chemistry), University of California Berkeley, 1994
PhD (Biology), Massachusetts Institute of Technology, 2000

Specialty Certification

Postgraduate Training

Postdoctoral Fellow, Department of Genetics, Harvard Medical School, 2000-05

Awards and Honors

NIH Training Grant Appointment, 1994
NIH-NIAID NRSA Fellowship, 2000
MARCE Career Development Grant, 2007
Faculty of 1000 Medicine, Biodefense Section, 2008
BWF Investigator in the Pathogenesis of Infectious Diseases, 2011
Montague Award, 2013
Penn Fellow, 2014
John Morgan Society, 2017
Fellow, American Academy of Microbiology, 2018
Board Member, Society for Functional Precision Medicine, 2018-2021
Stanley Cohen Award, 2019
Matis Family Award, 2021
Fellow, American Association for the Advancement of Science (AAAS), 2022

Memberships and Professional Organizations

Genetics Society of America, 2002-present
-------- Larry Sandler Award Committee, 2013
-------- Drosophilia Research Conference, Chair, 2014
American Society of Virology, 2005-present
-------- Workshop Convener, 2008, 2014
-------- Program Planning Committee, Abstract Selection, 2009-13
Immunology Graduate Group (IGG), University of Pennsylvania, 2005-present
-------- Executive Committee, 2014-present
-------- Student Advising, Co-Director, 2014-present
Cell and Molecular Biology Graduate Group (CAMB), University of Pennsylvania, 2006-present
-------- CAMB MVP Graduate Group, Executive Committee, 2015-present
Genomics and Computational Biology Graduate Group, University of Pennsylvania, 2006-present
American Association of Immunology, 2009-present
-------- Major Symposium Organizer, 2019-present
Biochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania, 2011-present
MRC-Medical Research Council, Grant Reviewer, 2012
European Research Council, Grant Reviewer, “Ideas,” 2013
NIH
-------- NIH Study Section, NIH/NIAID (AITRC), Ad Hoc, 2007
-------- NIH Roadmap CPSF Workshop, Chair, 2008
-------- NIH Study Section, NHGRI ZHG1HGR-M, 2011
-------- NIH Study Section, NIAID ZAI1 RRS, 2012
-------- NIH Study Section, NIGMS ZRG1 CB-R, Ad Hoc, 2012
-------- NIH Study Section, NIAID VIRB, Ad Hoc, 2013-14; Member 2014-present
-------- MPSCoRe Working Group, 2021-present
National Science Foundation (NSF) Study Section, Ad Hoc, 2010, 2013, 2015
DOD DTRA Study Section, 2011
American Association for the Advancement of Science (AAAS), 2013-present
American Society for Microbiology (ASM), 2013-present
Keystone Symposia
-------- Meeting, Abstract Selection, Meeting Convener, 2013-14
-------- Inaugural Organizer, “Intrinsic Defenses and Counterdefenses,” 2018
University of Pennsylvania Biomedical Graduate Studies, Biostatistics Curriculum Committee, 2013-14
Abramson Cancer Center, Penn Medicine, 2017-present
Viruses International Conferences, Organizer, 2018
International Advisory Board (IAB) for Perelman School of Medicine at the University of Pennsylvania
-------- CRISPR Core, 2019-present
-------- Electron Microscopy Core, 2019-present
University of Pittsburgh, Center for Vaccines Research, External Reviewer, 2019-present
Committee for Drosophilia Research & Screening Center, Executive Advisory Committee, 2020-present
NCATS Scientific Review, Ad Hoc, 2020
Pharmacology Graduate Group, University of Pennsylvania, 2020-present
Preclinical Therapeutic In Vitro Expert Panel for Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), 2020-present
Provost Leadership Academy, University of Pennsylvania, 2020-present
Society for Laboratory Automation and Screening (SLAS), Organizer for Precision Medicine, 2021
American Association of Immunologists (AAI), Abstract Programming Chair, 2022-present
DMM 2023 Meeting London, “Infectious Diseases and Therapies: Insights from Host-Pathogen Evolution,” 2022
RNA Society, RNA 2022 Session Chair, 2022-present
Scialog, Facilitator, “Mitigating Zoonotic Threats,” 2022-present

Web Links

Selected Publications

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