Penghua Wang, Ph.D.Assistant Professor
- Education & Training
- Committees & Organizations
- Research Opportunities
- Lab Rotations
Research interest: Innate Immunity, Viral Immunology, Mosquito-Borne Viral Disease, Respiratory Viral Disease, COVID-19, SARS-CoV-2.
Research support: NIH R01AI132526, R21AI155820
|B.Sc.||Sun Yat-sen University||Biochemistry|
|Ph.D.||The National University of Singapore||Biochemistry|
|Postdoctoral||Yale University||Postdoctoral Associate|
|Name of Award/Honor||Awarding Organization|
|COVID-19 Heroes-2020 Fall||UConn Health|
|Career Development Award||Northeast Biodefense Center, NIAID|
Immunity to Viral Infection
|Name & Description||Category||Role||Type||Scope||Start Year||End Year|
|PRMRP_VID4, Congressionally Directed Medical Research Programs, Department of Defense||Study Section||ad hoc member||External||National||2022||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||Research Committee||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||Research Committee||Grant Reviewer||External||International||2014|
My laboratory is interested in host-virus interactions, with a focus on RNA viruses in vivo and in vitro. Specifically, we attempt to understand pathogenic mechanisms of viral infection at the cellular and animal levels, and study the molecular function of host genes that influence viral pathogenesis and the disease outcomes. On the host end, we are keen on the innate immune system, detection of viruses and initiation of innate antiviral immune responses. On the viral end, we hope to understand the mechanisms of immune evasion and modulation of cellular functions by viral proteins.
1. The physiological functions of UBXNs in antiviral immunity. The human genome encodes 13 ubiquitin regulatory X (UBX) domain-containing proteins, designated UBXNs. The UBX domain shares weak homology with ubiquitin at the protein level and adopts the same three dimensional fold as ubiquitin. A number of UBXNs have been shown to bind to multiple E3 ubiquitin ligases and the ATPase associated with various cellular activities (AAA ATPase), p97, which is highly conserved across species and involved in diverse cellular processes, including ER-associated degradation (ERAD), vesicle fusion/membrane trafficking, and cell cycle. We and other research groups have recently shown that several UBXNs regulate the pattern recognition receptor (PRR) signaling including the viral RNA sensor RIG-I – MAVS axis (Retinoic acid Inducible Gene-Mitochondrial Antiviral Viral Signaling), the dsDNA sensor cGAS-STING axis (cyclic di-GMP-AMP Synthase-- Stimulator of Interferon Genes), and NF-kB signaling pathways. We are now elucidating the physiological functions of several UBXNs (Ubxn1, Ubxn3b and Ubxn9) during viral infection (arthritogenic alpahviruses: Chikungunya and O’nyong nyong, respiratory viruses: influenza and SARS-CoV-2) in tamoxifen-inducible gene knockout mice.
2. The roles of E3 ubiquitin ligases in viral pathogenesis and immune regulation. Ubiquitination is one of the best characterized and most important post-translational modifications that controls protein function and/or fate and impacts almost all cellular pathways, including viral pathogenesis. Ubiquitination is executed by three enzymes: ubiquitin-activating E1 (two genes in human genome), ubiquitin-conjugating E2 (~40 genes), and ubiquitin E3 ligases (~500) that determine substrate specificity. The ubiquitin-conjugating system impacts viral pathogenesis either directly by interfering with viral life cycle (including entry, replication, translation, assembly, egress) or indirectly by regulating antiviral immune responses. The host ubiquitination machinery can also be co-opted by viruses to complete their life cycle. We have generated a library of 374 individual E3 ligase knockout cell lines using CRSIPR-Cas9 and now systemically examining their functions in pattern recognition receptor (PRR) signaling and viral pathogenesis (influenza, SARS-CoV-2).
Accepting Lab Rotation Students: Fall 2022 and Spring 2023
Quantitative Analysis of B-Cell Subpopulations in Bone Marrow by Flow Cytometry.
Methods in molecular biology (Clifton, N.J.) 2023 Jan;258571-77
UBXN3B Controls Immunopathogenesis of Arthritogenic Alphaviruses by Maintaining Hematopoietic Homeostasis.
mBio 2022 Nov;e0268722
Neighboring mutation-mediated enhancement of dengue virus infectivity and spread.
EMBO reports 2022 Nov;23(11):e55671
A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry.
mBio 2022 Aug;13(4):e0148522
A volatile from the skin microbiota of flavivirus-infected hosts promotes mosquito attractiveness.
Cell 2022 Jun;
Lipases secreted by a gut bacterium inhibit arbovirus transmission in mosquitoes.
PLoS pathogens 2022 Jun;18(6):e1010552
A glucose-like metabolite deficient in diabetes inhibits cellular entry of SARS-CoV-2.
Nature metabolism 2022 May;4(5):547-558
Intrinsic cardiac adrenergic cells contribute to LPS-induced myocardial dysfunction.
Communications biology 2022 Jan;5(1):96
A human-blood-derived microRNA facilitates flavivirus infection in fed mosquitoes.
Cell reports 2021 Dec;37(11):110091
STAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy.
Cells 2021 Nov;10(11):
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):
Mitofusin-2 regulates leukocyte adhesion and β2 integrin activation.
Journal of leukocyte biology 2021 Sep;
Differential roles of RIG-I like receptors in SARS-CoV-2 infection.
Military Medical Research 2021 Sep;8(1):49
A critical role for MSR1 in vesicular stomatitis virus infection of the central nervous system.
iScience 2021 Jun;24(6):102678
UBX Domain Protein 6 Positively Regulates JAK-STAT1/2 Signaling.
Journal of immunology (Baltimore, Md. : 1950) 2021 Jun;206(11):2682-2691
Glucose-mediated proliferation of a gut commensal bacterium promotes Plasmodium infection by increasing mosquito midgut pH.
Cell reports 2021 Apr;35(3):108992
Interaction of Viruses with the Insect Intestine.
Annual review of virology 2021 Apr;
Pharmacological Inhibition of STAT6 Ameliorates Myeloid Fibroblast Activation and Alternative Macrophage Polarization in Renal Fibrosis.
Frontiers in immunology 2021 Jan;12735014
A critical role for STING signaling in limiting pathogenesis of Chikungunya virus.
The Journal of infectious diseases 2020 Nov;
CXCL10 Signaling Contributes to the Pathogenesis of Arthritogenic Alphaviruses.
Viruses 2020 Nov;12(11):
Mechanisms of SARS-CoV-2 Transmission and Pathogenesis.
Trends Immunol 2020 Oct;
Macrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy in mice.
Communications biology 2020 Oct;3(1):556
Roles of Symbiotic Microorganisms in Arboviral Infection of Arthropod Vectors.
Trends in parasitology 2020 Jul;36(7):607-615
A mosquito salivary protein promotes flavivirus transmission by activation of autophagy.
Nature communications 2020 Jan;11(1):260
Progress towards Understanding the Mosquito-Borne Virus Life Cycle.
Trends in parasitology 2019 Dec;35(12):1009-1017
Host serum iron modulates dengue virus acquisition by mosquitoes.
Nature microbiology 2019 Sep;
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
Chikungunya Virus and (Re-) Emerging Alphaviruses.
Viruses 2019 Aug;11(9):
The GRA15 protein from Toxoplasma gondii enhances host defense responses by activating the interferon stimulator STING.
The Journal of biological chemistry 2019 Aug;
Endogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression.
mBio 2019 Jul;10(4):
Identification of genetic variations in Necator americanus through resequencing by whole genome amplification.
The Journal of international medical research 2019 Jul;300060519862069
Aedes mosquitoes acquire and transmit Zika virus by breeding in contaminated aquatic environments.
Nature communications 2019 Mar;10(1):1324
HIPK2 is necessary for type I interferon-mediated antiviral immunity.
Science signaling 2019 Mar;12(573):
Arbovirus lifecycle in mosquito: acquisition, propagation and transmission.
Expert reviews in molecular medicine 2019 Mar;21e1
Genetic Determinants of the Re-Emergence of Arboviral Diseases.
Viruses 2019 Feb;11(2):
A Gut Commensal Bacterium Promotes Mosquito Permissiveness to Arboviruses.
Cell host & microbe 2019 Jan;25(1):101-112.e5
Interferon-stimulated TRIM69 interrupts dengue virus replication by ubiquitinating viral nonstructural protein 3.
PLoS pathogens 2018 Aug;14(8):e1007287
UBXN3B positively regulates STING-mediated antiviral immune responses.
Nature communications 2018 Jun;9(1):2329
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
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
Zika Virus Non-structural Protein 4A Blocks the RLR-MAVS Signaling.
Frontiers in microbiology 2018 Jan;91350
Blood meal acquisition enhances arbovirus replication in mosquitoes through activation of the GABAergic system.
Nature communications 2017 Nov;8(1):1262
Sophoraflavenone G Restricts Dengue and Zika Virus Infection via RNA Polymerase Interference.
Viruses 2017 Oct;9(10):
Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells.
Nature 2017 Jun;546(7660):667-670
An essential role of PI3K in the control of West Nile virus infection.
Scientific reports 2017 Jun;7(1):3724
Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes.
Nature 2017 May;545(7655):482-486
A Mesh-Duox pathway regulates homeostasis in the insect gut.
Nature microbiology 2017 Mar;217020
Multiple UBXN family members inhibit retrovirus and lentivirus production and canonical NFκΒ signaling by stabilizing IκBα.
PLoS pathogens 2017 Feb;13(2):e1006187
Interleukin-17A Promotes CD8+ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance.
Journal of virology 2017 Jan;91(1):
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
Flavivirus NS1 protein in infected host sera enhances viral acquisition by mosquitoes.
Nature microbiology 2016 Jun;1(9):16087
Mosquito C-type lectins maintain gut microbiome homeostasis.
Nature microbiology 2016 May;1
Mosquito C-type lectins maintain gut microbiome homeostasis.
Nature microbiology 2016 Mar;116023
Exploration of West Nile Virus Infection in Mouse Models.
Methods in molecular biology (Clifton, N.J.) 2016 Jan;143571-81
Glycosphingolipid GM3 is Indispensable for Dengue Virus Genome Replication.
International journal of biological sciences 2016 Jan;12(7):872-83
Nlrp6 regulates intestinal antiviral innate immunity.
Science (New York, N.Y.) 2015 Nov;350(6262):826-30
A neuron-specific antiviral mechanism prevents lethal flaviviral infection of mosquitoes.
PLoS pathogens 2015 Apr;11(4):e1004848
Complement-related proteins control the flavivirus infection of Aedes aegypti by inducing antimicrobial peptides.
PLoS pathogens 2014 Apr;10(4):e1004027
Transmission-blocking antibodies against mosquito C-type lectins for dengue prevention.
PLoS pathogens 2014 Feb;10(2):e1003931
Mosquito saliva serine protease enhances dissemination of dengue virus into the mammalian host.
Journal of virology 2014 Jan;88(1):164-75
ELF4 is critical for induction of type I interferon and the host antiviral response.
Nature immunology 2013 Dec;14(12):1237-46
UBXN1 interferes with Rig-I-like receptor-mediated antiviral immune response by targeting MAVS.
Cell reports 2013 Apr;3(4):1057-70
IL-22 signaling contributes to West Nile encephalitis pathogenesis.
PloS one 2012 Jan;7(8):e44153
ISG15 facilitates cellular antiviral response to dengue and west nile virus infection in vitro.
Virology journal 2011 Oct;8468
prM-antibody renders immature West Nile virus infectious in vivo.
The Journal of general virology 2011 Oct;92(Pt 10):2281-5
Alterations in the Aedes aegypti transcriptome during infection with West Nile, dengue and yellow fever viruses.
PLoS pathogens 2011 Sep;7(9):e1002189
An in vivo transfection approach elucidates a role for Aedes aegypti thioester-containing proteins in flaviviral infection.
PloS one 2011 Jan;6(7):e22786
Dengue virus capsid protein binds core histones and inhibits nucleosome formation in human liver cells.
PloS one 2011 Jan;6(9):e24365
Tick histamine release factor is critical for Ixodes scapularis engorgement and transmission of the lyme disease agent.
PLoS pathogens 2010 Nov;6(11):e1001205
Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I.
Nature immunology 2010 Oct;11(10):912-9
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
Antibodies against a tick protein, Salp15, protect mice from the Lyme disease agent.
Cell host & microbe 2009 Nov;6(5):482-92
IL-10 signaling blockade controls murine West Nile virus infection.
PLoS pathogens 2009 Oct;5(10):e1000610
The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi.
PLoS pathogens 2009 May;5(5):e1000447
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
Matrix metalloproteinase 9 facilitates West Nile virus entry into the brain.
Journal of virology 2008 Sep;82(18):8978-85
Icam-1 participates in the entry of west nile virus into the central nervous system.
Journal of virology 2008 Apr;82(8):4164-8
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
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
AAA ATPases regulate membrane association of yeast oxysterol binding proteins and sterol metabolism.
The EMBO journal 2005 Sep;24(17):2989-99
Molecular characterization of Osh6p, an oxysterol binding protein homolog in the yeast Saccharomyces cerevisiae.
The FEBS journal 2005 Sep;272(18):4703-15
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
Mosquito-borne pathogens hijack human body odors to promote transmission.
Science China. Life sciences 2022 Nov;
Mosquito Defense Strategies against Viral Infection.
Trends in parasitology 2016 Mar;32(3):177-186
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|