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Penghua Wang, PhDAssociate Professor
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- Overview
- Education & Training
- Clinical Interests
- Teaching
- Committees & Organizations
- Research
- Research Opportunities
- Lab Rotations
- Publications
- Presentations
Research interest: Pattern Recognition Receptors, Inflammasomes, Ubiquitination, Mosquito-Borne Viruses, SARS-CoV-2.
Research support: NIH R01AI132526, R21AI170981, R21AI177623
Education
Post-Graduate Training
Awards
| Degree | Institution | Major |
|---|---|---|
| BSc | Sun Yat-sen University | Biochemistry |
| PhD | The National University of Singapore | Biochemistry |
Post-Graduate Training
| Training | Institution | Specialty |
|---|---|---|
| Postdoctoral | Yale University | Postdoctoral Associate |
Awards
| Name of Award/Honor | Awarding Organization |
|---|---|
| COVID-19 Heroes-2020 Fall | UConn Health |
| Career Development Award | Northeast Biodefense Center, NIAID |
N/A
Immunity to Viral Infection MEDS 5329, MEDS 5335
| Name & Description | Category | Role | Type | Scope | Start Year | End Year |
|---|---|---|---|---|---|---|
| Congressionally Directed Medical Research Programs, DoD | Study Section | ad hoc member | External | National | 2022 | |
| ZRG1_IDIA-T(90)S, NIH | Study Section | ad hoc member | External | National | 2022 | 2022 |
| ZGM1_RCB_W, NIH | Study Section | ad hoc member | External | National | 2022 | 2022 |
| ZAI-FDS-W, NIH, Meeting on 01/14/2021 | Study Section | Ad hoc member | External | National | 2021 | 2021 |
| Biomedical Sciences PhD Program Admission Committee | Education Committee | Member | UConn Health | University | 2020 | 2024 |
| French Agence Nationale de la Recherche-ANR | Study Section | Grant Reviewer | External | International | 2019 | 2019 |
| NIH, Topics on Virology | Study Section | Grant Reviewer | External | National | 2019 | |
| Viruses | Editorial Board | Guest Editor | External | International | 2018 | 2019 |
| American Association of Immunologists | Professional/Scientific Organization | Member | External | National | 2018 | |
| Antimicrobial Agents and Chemotherapy | Professional/Scientific Journal | Reviewing Editor | External | International | 2017 | 2023 |
| NIH, Non-HIV Infectious Agent Detection/Diagnostics, Food Safety, Sterilization/Disinfection and Bioremediation Special Emphasis Panel | Study Section | Ad hoc member | External | National | 2016 | |
| American Society For Virology | Professional/Scientific Organization | Regular Member | External | National | 2015 | |
| Frontiers in Cellular and Infection Microbiology, Frontiers in Virology | Professional/Scientific Journal | Associate Editor | External | International | 2015 | |
| American Society for Virology | Professional/Scientific Organization | Member | External | National | 2015 | |
| Hongkong Health and Medical Research Fund | Study Section | Grant Reviewer | External | International | 2014 | |
| Journal of Virology | Editorial Board | Reviewing Editor | External | International |
My research focuses on pattern recognition receptor signaling pathways and pathogenesis of mosquito-borne RNA viruses. On the host end, I am interested in cellular regulation of the major viral RNA (RIG-I like receptors)- and DNA (cGAS-STING)-sensing pathways. I am also keen on the non-canonical inflammasome. On the viral end, I attempt to understand the mechanisms of immune evasion and modulation of cellular functions by viral proteins.
Project 1. Cellular regulation of inflammasomes. Inflammasomes are large cytosolic multiprotein complexes formed in response to infections and cellular stresses, leading to auto-activation of inflammatory caspases, production of inflammatory mediators and pyroptosis. Hyperactive inflammasomes are involved in the pathogenesis of sepsis, a life-threatening illness accounting for >250,000 deaths each year in the United States. We are interested in identifying and characterizing novel cellular regulators of inflammasome signaling. We have recently generated 375 E3 ubiquitin ligase knockout cell lines by CRISPR-Cas9, completed screening these knockouts for the non-canonical inflammasome, and identified several promising candidates awaiting to be characterized in-depth.
Project 2. Cellular regulation of pattern recognition receptors (PRR). RIG-I like receptors (RLRs) and cGAS-STING are major cytoplasmic viral RNA and DNA sensors essential for triggering antiviral immune responses. However, hyperactive PRR signaling may contribute to autoinflammatory diseases. By screening 375 E3 ubiquitin ligase knockout cell lines, we have identified several promising regulators of RLR and STING signaling awaiting to be characterized in-depth. We are also investigating how glucose transporters regulate viral pathogenesis and RLR signaling.
Project 3. Manipulation of host skin microbiota by mosquito-borne viruses. Mosquito-borne viruses (dengue, Zika, Chikungunya etc.) infect roughly ~400 million people worldwide. The host-seeking motivation of mosquitoes in response to host cues is not only essential for female mosquito reproduction, but also for arbovirus transmission. We are investigating how arboviruses manipulate host skin microbiota to produce mosquito-attracting odors and promote transmission.
Accepting Lab Rotation Students: Fall Block 2024, Spring 1 and 2 Block 2025
Journal Articles
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Autoregulated splicing of TRA2β programs T cell fate in response to antigen-receptor stimulation.
Science (New York, N.Y.) 2024 Sep;385(6714):eadj1979
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UBXN3B is crucial for B lymphopoiesis.
EBioMedicine 2024 Jul;106105248
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A naturally isolated symbiotic bacterium suppresses flavivirus transmission by Aedes mosquitoes.
Science (New York, N.Y.) 2024 Apr;384(6693):eadn9524
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An evolutionarily conserved ubiquitin ligase drives infection and transmission of flaviviruses.
Proceedings of the National Academy of Sciences of the United States of America 2024 Apr;121(16):e2317978121
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A mosquito salivary protein-driven influx of myeloid cells facilitates flavivirus transmission.
The EMBO journal 2024 Feb;
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UBR5 promotes antiviral immunity by disengaging the transcriptional brake on RIG-I like receptors.
Nature communications 2024 Jan;15(1):780
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A Bayesian spatiotemporal approach to modelling arboviral diseases in Mexico.
Transactions of the Royal Society of Tropical Medicine and Hygiene 2023 Dec;117(12):867-874
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Baseline Gut Microbiome Signatures Correlate with Immunogenicity of SARS-CoV-2 mRNA Vaccines.
International journal of molecular sciences 2023 Jul;24(14):
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An mRNA-based T-cell-inducing antigen strengthens COVID-19 vaccine against SARS-CoV-2 variants.
Nature communications 2023 May;14(1):2962
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Jumonji domain-containing protein-3 (JMJD3) promotes myeloid fibroblast activation and macrophage polarization in kidney fibrosis.
British Journal of Pharmacology 2023 Apr;180(17):2250-2265
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Quantitative Analysis of B-Cell Subpopulations in Bone Marrow by Flow Cytometry.
Methods in molecular biology (Clifton, N.J.) 2023 Jan;258571-77
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UBXN3B Controls Immunopathogenesis of Arthritogenic Alphaviruses by Maintaining Hematopoietic Homeostasis.
mBio 2022 Nov;e0268722
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Neighboring mutation-mediated enhancement of dengue virus infectivity and spread.
EMBO reports 2022 Nov;23(11):e55671
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A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry.
mBio 2022 Aug;13(4):e0148522
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A volatile from the skin microbiota of flavivirus-infected hosts promotes mosquito attractiveness.
Cell 2022 Jun;
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Lipases secreted by a gut bacterium inhibit arbovirus transmission in mosquitoes.
PLoS pathogens 2022 Jun;18(6):e1010552
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A glucose-like metabolite deficient in diabetes inhibits cellular entry of SARS-CoV-2.
Nature metabolism 2022 May;4(5):547-558
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Intrinsic cardiac adrenergic cells contribute to LPS-induced myocardial dysfunction.
Communications biology 2022 Jan;5(1):96
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A human-blood-derived microRNA facilitates flavivirus infection in fed mosquitoes.
Cell reports 2021 Dec;37(11):110091
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STAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy.
Cells 2021 Nov;10(11):
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A mutation-mediated evolutionary adaptation of Zika virus in mosquito and mammalian host.
Proceedings of the National Academy of Sciences of the United States of America 2021 Oct;118(42):
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Mitofusin-2 regulates leukocyte adhesion and β2 integrin activation.
Journal of leukocyte biology 2021 Sep;
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Differential roles of RIG-I like receptors in SARS-CoV-2 infection.
Military Medical Research 2021 Sep;8(1):49
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A critical role for MSR1 in vesicular stomatitis virus infection of the central nervous system.
iScience 2021 Jun;24(6):102678
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UBX Domain Protein 6 Positively Regulates JAK-STAT1/2 Signaling.
Journal of immunology (Baltimore, Md. : 1950) 2021 Jun;206(11):2682-2691
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Glucose-mediated proliferation of a gut commensal bacterium promotes Plasmodium infection by increasing mosquito midgut pH.
Cell reports 2021 Apr;35(3):108992
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Interaction of Viruses with the Insect Intestine.
Annual review of virology 2021 Apr;
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Pharmacological Inhibition of STAT6 Ameliorates Myeloid Fibroblast Activation and Alternative Macrophage Polarization in Renal Fibrosis.
Frontiers in immunology 2021 Jan;12735014
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A critical role for STING signaling in limiting pathogenesis of Chikungunya virus.
The Journal of infectious diseases 2020 Nov;
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CXCL10 Signaling Contributes to the Pathogenesis of Arthritogenic Alphaviruses.
Viruses 2020 Nov;12(11):
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Mechanisms of SARS-CoV-2 Transmission and Pathogenesis.
Trends Immunol 2020 Oct;
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Macrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy in mice.
Communications biology 2020 Oct;3(1):556
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Roles of Symbiotic Microorganisms in Arboviral Infection of Arthropod Vectors.
Trends in parasitology 2020 Jul;36(7):607-615
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A mosquito salivary protein promotes flavivirus transmission by activation of autophagy.
Nature communications 2020 Jan;11(1):260
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Progress towards Understanding the Mosquito-Borne Virus Life Cycle.
Trends in parasitology 2019 Dec;35(12):1009-1017
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Host serum iron modulates dengue virus acquisition by mosquitoes.
Nature microbiology 2019 Sep;
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The Nuclear Matrix Protein SAFA Surveils Viral RNA and Facilitates Immunity by Activating Antiviral Enhancers and Super-enhancers.
Cell host & microbe 2019 Sep;26(3):369-384.e8
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Chikungunya Virus and (Re-) Emerging Alphaviruses.
Viruses 2019 Aug;11(9):
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The GRA15 protein from Toxoplasma gondii enhances host defense responses by activating the interferon stimulator STING.
The Journal of biological chemistry 2019 Aug;
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Endogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression.
mBio 2019 Jul;10(4):
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Identification of genetic variations in Necator americanus through resequencing by whole genome amplification.
The Journal of international medical research 2019 Jul;300060519862069
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Aedes mosquitoes acquire and transmit Zika virus by breeding in contaminated aquatic environments.
Nature communications 2019 Mar;10(1):1324
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HIPK2 is necessary for type I interferon-mediated antiviral immunity.
Science signaling 2019 Mar;12(573):
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Arbovirus lifecycle in mosquito: acquisition, propagation and transmission.
Expert reviews in molecular medicine 2019 Mar;21e1
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Genetic Determinants of the Re-Emergence of Arboviral Diseases.
Viruses 2019 Feb;11(2):
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A Gut Commensal Bacterium Promotes Mosquito Permissiveness to Arboviruses.
Cell host & microbe 2019 Jan;25(1):101-112.e5
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Interferon-stimulated TRIM69 interrupts dengue virus replication by ubiquitinating viral nonstructural protein 3.
PLoS pathogens 2018 Aug;14(8):e1007287
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UBXN3B positively regulates STING-mediated antiviral immune responses.
Nature communications 2018 Jun;9(1):2329
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Trefoil Factor 3, Cholinesterase and Homocysteine: Potential Predictors for Parkinson's Disease Dementia and Vascular Parkinsonism Dementia in Advanced Stage.
Aging and disease 2018 Feb;9(1):51-65
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Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1.
Autophagy 2018 Jan;14(2):336-346
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Zika Virus Non-structural Protein 4A Blocks the RLR-MAVS Signaling.
Frontiers in microbiology 2018 Jan;91350
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Blood meal acquisition enhances arbovirus replication in mosquitoes through activation of the GABAergic system.
Nature communications 2017 Nov;8(1):1262
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Sophoraflavenone G Restricts Dengue and Zika Virus Infection via RNA Polymerase Interference.
Viruses 2017 Oct;9(10):
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Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells.
Nature 2017 Jun;546(7660):667-670
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An essential role of PI3K in the control of West Nile virus infection.
Scientific reports 2017 Jun;7(1):3724
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Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes.
Nature 2017 May;545(7655):482-486
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A Mesh-Duox pathway regulates homeostasis in the insect gut.
Nature microbiology 2017 Mar;217020
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Multiple UBXN family members inhibit retrovirus and lentivirus production and canonical NFκΒ signaling by stabilizing IκBα.
PLoS pathogens 2017 Feb;13(2):e1006187
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Interleukin-17A Promotes CD8+ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance.
Journal of virology 2017 Jan;91(1):
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TLR8 Couples SOCS-1 and Restrains TLR7-Mediated Antiviral Immunity, Exacerbating West Nile Virus Infection in Mice.
Journal of immunology (Baltimore, Md. : 1950) 2016 Dec;197(11):4425-4435
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Flavivirus NS1 protein in infected host sera enhances viral acquisition by mosquitoes.
Nature microbiology 2016 Jun;1(9):16087
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Mosquito C-type lectins maintain gut microbiome homeostasis.
Nature microbiology 2016 May;1
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Mosquito C-type lectins maintain gut microbiome homeostasis.
Nature microbiology 2016 Mar;116023
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Exploration of West Nile Virus Infection in Mouse Models.
Methods in molecular biology (Clifton, N.J.) 2016 Jan;143571-81
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Glycosphingolipid GM3 is Indispensable for Dengue Virus Genome Replication.
International journal of biological sciences 2016 Jan;12(7):872-83
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Nlrp6 regulates intestinal antiviral innate immunity.
Science (New York, N.Y.) 2015 Nov;350(6262):826-30
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A neuron-specific antiviral mechanism prevents lethal flaviviral infection of mosquitoes.
PLoS pathogens 2015 Apr;11(4):e1004848
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Complement-related proteins control the flavivirus infection of Aedes aegypti by inducing antimicrobial peptides.
PLoS pathogens 2014 Apr;10(4):e1004027
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Transmission-blocking antibodies against mosquito C-type lectins for dengue prevention.
PLoS pathogens 2014 Feb;10(2):e1003931
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Mosquito saliva serine protease enhances dissemination of dengue virus into the mammalian host.
Journal of virology 2014 Jan;88(1):164-75
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ELF4 is critical for induction of type I interferon and the host antiviral response.
Nature immunology 2013 Dec;14(12):1237-46
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UBXN1 interferes with Rig-I-like receptor-mediated antiviral immune response by targeting MAVS.
Cell reports 2013 Apr;3(4):1057-70
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IL-22 signaling contributes to West Nile encephalitis pathogenesis.
PloS one 2012 Jan;7(8):e44153
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ISG15 facilitates cellular antiviral response to dengue and west nile virus infection in vitro.
Virology journal 2011 Oct;8468
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prM-antibody renders immature West Nile virus infectious in vivo.
The Journal of general virology 2011 Oct;92(Pt 10):2281-5
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Alterations in the Aedes aegypti transcriptome during infection with West Nile, dengue and yellow fever viruses.
PLoS pathogens 2011 Sep;7(9):e1002189
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An in vivo transfection approach elucidates a role for Aedes aegypti thioester-containing proteins in flaviviral infection.
PloS one 2011 Jan;6(7):e22786
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Dengue virus capsid protein binds core histones and inhibits nucleosome formation in human liver cells.
PloS one 2011 Jan;6(9):e24365
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Tick histamine release factor is critical for Ixodes scapularis engorgement and transmission of the lyme disease agent.
PLoS pathogens 2010 Nov;6(11):e1001205
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Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I.
Nature immunology 2010 Oct;11(10):912-9
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A C-type lectin collaborates with a CD45 phosphatase homolog to facilitate West Nile virus infection of mosquitoes.
Cell 2010 Sep;142(5):714-25
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Antibodies against a tick protein, Salp15, protect mice from the Lyme disease agent.
Cell host & microbe 2009 Nov;6(5):482-92
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IL-10 signaling blockade controls murine West Nile virus infection.
PLoS pathogens 2009 Oct;5(10):e1000610
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The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi.
PLoS pathogens 2009 May;5(5):e1000447
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Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in human synovial cells through a protein moiety.
Microbes and infection 2008 Oct;10(12-13):1300-8
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Matrix metalloproteinase 9 facilitates West Nile virus entry into the brain.
Journal of virology 2008 Sep;82(18):8978-85
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Icam-1 participates in the entry of west nile virus into the central nervous system.
Journal of virology 2008 Apr;82(8):4164-8
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Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis.
The Journal of experimental medicine 2008 Jan;205(1):133-41
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A differential role for BB0365 in the persistence of Borrelia burgdorferi in mice and ticks.
The Journal of infectious diseases 2008 Jan;197(1):148-55
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AAA ATPases regulate membrane association of yeast oxysterol binding proteins and sterol metabolism.
The EMBO journal 2005 Sep;24(17):2989-99
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Molecular characterization of Osh6p, an oxysterol binding protein homolog in the yeast Saccharomyces cerevisiae.
The FEBS journal 2005 Sep;272(18):4703-15
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Simvastatin reverses the downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex of 6-hydroxydopamine-induced Parkinsonian rats.
Brain research 2005 May;1045(1-2):229-33
Reviews
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Mosquito-borne pathogens hijack human body odors to promote transmission.
Science China. Life sciences 2022 Nov;
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Mosquito Defense Strategies against Viral Infection.
Trends in parasitology 2016 Mar;32(3):177-186
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Innate immune control of West Nile virus infection.
Cellular microbiology 2011 Nov;13(11):1648-58
| Title or Abstract | Type | Sponsor/Event | Date/Year | Location |
|---|---|---|---|---|
| UBXN3B Controls B Lymphopoiesis via BLNK | Talk | American Society for Virology Annual Meeting | 2022 | Madison, Wisconsin, U.S |
| UBXNs, new players in antiviral immunity | Talk | Department of Virology, Mount Sinai School of Medicine | 2018 | New York City, NY |
| STING Controls Chikungunya Virus Infection and Pathogenesis | Talk | Shenzhen CDC, Tsinghua University | 2016 | Shenzhen, China |
| NOD Like Receptor 6: Not A Nod to Enteric Viruses | Talk | Department of Medicine, McGill University | 2016 | Montreal Canada |
| A critical role for STING in the control of Chikungunya virus pathogenesis | Poster | Keystone Symposium | 2016 | Austin, TX, USA |