Megan L Stanifer

Megan L Stanifer,

Assistant Professor

Department: Molecular Genetics & Microbiology
Business Phone: (352) 273-7533
Business Email: m.stanifer@ufl.edu

Research Profile

Intestinal epithelial cells are in constant contact with the ever-present commensal flora. This leaves them with a complex task of maintaining a fine balance between tolerating the microbiota and being ready to respond to invading pathogens. Intestinal cells are polarized with an apical side facing the lumen of the gut and a basolateral side facing the sterile lamina propria. Our work has uncovered that one method used by human intestinal epithelial cells (hIECs) to avoid over stimulation is that they polarize the pathogen-recognition receptor TLR‑3 to the basolateral side of hIECs to avoid over detection of the commensal bacteria. Our group continues to investigate the molecular mechanisms used by hIECs to maintain immune-homeostasis and how these mechanisms are mis-regulated in patients with inflammatory bowel disease by employing organoid cultures, live-cell imaging, and single cell sequencing. Additionally, we are now extending our observations in hIECs to additional mucosal tissues (e.g. the lung and genital tract) to determine if all tissues that act as a protect barrier use similar mechanisms to detect and fight invading pathogens while tolerating the presence of the commensal flora.

Open Researcher and Contributor ID (ORCID)

0000-0002-5606-1297

Publications

2022
A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells.
Cell metabolism. 34(6):857-873.e9 [DOI] 10.1016/j.cmet.2022.04.009. [PMID] 35561674.
2022
A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling.
Cell. 185(13):2354-2369.e17 [DOI] 10.1016/j.cell.2022.04.028. [PMID] 35568036.
2022
A model for network-based identification and pharmacological targeting of aberrant, replication-permissive transcriptional programs induced by viral infection.
Communications biology. 5(1) [DOI] 10.1038/s42003-022-03663-8. [PMID] 35854100.
2022
A Model for Network-Based Identification and Pharmacological Targeting of Aberrant, Replication-Permissive Transcriptional Programs Induced by Viral Infection.
Research square. [DOI] 10.21203/rs.3.rs-1287631/v1. [PMID] 35132404.
2022
Author Correction: Multivalent 9-O-Acetylated-sialic acid glycoclusters as potent inhibitors for SARS-CoV-2 infection
Nature Communications. 13(1) [DOI] 10.1038/s41467-022-31290-8. [PMID] 35750667.
2022
Ex vivo and in vivo suppression of SARS-CoV-2 with combinatorial AAV/RNAi expression vectors
Molecular Therapy. 30(5):2005-2023 [DOI] 10.1016/j.ymthe.2022.01.024. [PMID] 35038579.
2022
Genetic regulation of OAS1 nonsense-mediated decay underlies association with COVID-19 hospitalization in patients of European and African ancestries.
Nature genetics. 54(8):1103-1116 [DOI] 10.1038/s41588-022-01113-z. [PMID] 35835913.
2022
Increased Sensitivity of SARS-CoV-2 to Type III Interferon in Human Intestinal Epithelial Cells.
Journal of virology. 96(7) [DOI] 10.1128/jvi.01705-21. [PMID] 35262371.
2022
Mapping the epithelial–immune cell interactome upon infection in the gut and the upper airways
npj Systems Biology and Applications. 8(1) [DOI] 10.1038/s41540-022-00224-x. [PMID] 35501398.
2022
Multivalent 9-O-Acetylated-sialic acid glycoclusters as potent inhibitors for SARS-CoV-2 infection
Nature Communications. 13(1) [DOI] 10.1038/s41467-022-30313-8. [PMID] 35538121.
2022
The FDA-Approved Drug Cobicistat Synergizes with Remdesivir To Inhibit SARS-CoV-2 Replication In Vitro and Decreases Viral Titers and Disease Progression in Syrian Hamsters.
mBio. 13(2) [DOI] 10.1128/mbio.03705-21. [PMID] 35229634.
2022
The link between menin and pleiotrophin in the tumor biology of pancreatic neuroendocrine neoplasms.
Cancer science. 113(5):1575-1586 [DOI] 10.1111/cas.15301. [PMID] 35179814.
2021
Adapting Gastrointestinal Organoids for Pathogen Infection and Single Cell Sequencing under Biosafety Level 3 (BSL-3) Conditions.
Journal of visualized experiments : JoVE. (175) [DOI] 10.3791/62857. [PMID] 34570087.
2021
Conserved Induction of Distinct Antiviral Signalling Kinetics by Primate Interferon Lambda 4 Proteins.
Frontiers in immunology. 12 [DOI] 10.3389/fimmu.2021.772588. [PMID] 34868037.
2021
Functional comparison of MERS-coronavirus lineages reveals increased replicative fitness of the recombinant lineage 5
Nature Communications. 12(1) [DOI] 10.1038/s41467-021-25519-1. [PMID] 34493730.
2021
Genetic regulation of OAS1 nonsense-mediated decay underlies association with risk of severe COVID-19.
medRxiv : the preprint server for health sciences. [DOI] 10.1101/2021.07.09.21260221. [PMID] 34282422.
2021
Invasiveness of Escherichia coli Is Associated with an IncFII Plasmid
Pathogens. 10(12) [DOI] 10.3390/pathogens10121645. [PMID] 34959600.
2021
Microscopy-based assay for semi-quantitative detection of SARS-CoV-2 specific antibodies in human sera: A semi-quantitative, high throughput, microscopy-based assay expands existing approaches to measure SARS-CoV-2 specific antibody levels in human sera.
BioEssays : news and reviews in molecular, cellular and developmental biology. 43(3) [DOI] 10.1002/bies.202000257. [PMID] 33377226.
2021
SARS‐CoV‐2 infection remodels the host protein thermal stability landscape
Molecular Systems Biology. 17(2) [DOI] 10.15252/msb.202010188. [PMID] 33590968.
2021
Selective Janus kinase inhibition preserves interferon-λ–mediated antiviral responses
Science Immunology. 6(59) [DOI] 10.1126/sciimmunol.abd5318. [PMID] 33990378.
2021
Single‐cell analyses reveal SARS‐CoV‐2 interference with intrinsic immune response in the human gut
Molecular Systems Biology. 17(4) [DOI] 10.15252/msb.202110232. [PMID] 33904651.
2021
Single‐cell transcriptomics reveals immune response of intestinal cell types to viral infection
Molecular Systems Biology. 17(7) [DOI] 10.15252/msb.20209833. [PMID] 34309190.
2021
The endogenous cellular protease inhibitor SPINT2 controls SARS-CoV-2 viral infection and is associated to disease severity.
PLoS pathogens. 17(6) [DOI] 10.1371/journal.ppat.1009687. [PMID] 34181691.
2021
TMPRSS2 expression dictates the entry route used by SARS‐CoV‐2 to infect host cells
The EMBO Journal. 40(16) [DOI] 10.15252/embj.2021107821. [PMID] 34159616.
2020
3D Correlative Cryo-Structured Illumination Fluorescence and Soft X-ray Microscopy Elucidates Reovirus Intracellular Release Pathway.
Cell. 182(2):515-530.e17 [DOI] 10.1016/j.cell.2020.05.051. [PMID] 32610083.
2020
A colorimetric RT-LAMP assay and LAMP-sequencing for detecting SARS-CoV-2 RNA in clinical samples
Science Translational Medicine. 12(556) [DOI] 10.1126/scitranslmed.abc7075. [PMID] 32719001.
2020
Asymmetric distribution of TLR3 leads to a polarized immune response in human intestinal epithelial cells
Nature Microbiology. 5(1):181-191 [DOI] 10.1038/s41564-019-0594-3.
2020
Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells.
Cell reports. 32(1) [DOI] 10.1016/j.celrep.2020.107863. [PMID] 32610043.
2020
Development of Feline Ileum- and Colon-Derived Organoids and Their Potential Use to Support Feline Coronavirus Infection
Cells. 9(9) [DOI] 10.3390/cells9092085. [PMID] 32932592.
2020
Enhanced Uptake and Endosomal Release of LbL Microcarriers Functionalized with Reversible Fusion Proteins.
ACS applied bio materials. 3(3):1553-1567 [DOI] 10.1021/acsabm.9b01168. [PMID] 35021646.
2020
Importance of Type I and III Interferons at Respiratory and Intestinal Barrier Surfaces.
Frontiers in immunology. 11 [DOI] 10.3389/fimmu.2020.608645. [PMID] 33362795.
2020
Integrative Imaging Reveals SARS-CoV-2-Induced Reshaping of Subcellular Morphologies.
Cell host & microbe. 28(6):853-866.e5 [DOI] 10.1016/j.chom.2020.11.003. [PMID] 33245857.
2020
Interferons and viruses induce a novel primate-specific isoform dACE2 and not the SARS-CoV-2 receptor ACE2.
bioRxiv : the preprint server for biology. [DOI] 10.1101/2020.07.19.210955. [PMID] 32743577.
2020
Interferons and viruses induce a novel truncated ACE2 isoform and not the full-length SARS-CoV-2 receptor
Nature Genetics. 52(12):1283-1293 [DOI] 10.1038/s41588-020-00731-9. [PMID] 33077916.
2020
Novel Toscana Virus Reverse Genetics System Establishes NSs as an Antagonist of Type I Interferon Responses
Viruses. 12(4) [DOI] 10.3390/v12040400. [PMID] 32260371.
2020
NSs amyloid formation is associated with the virulence of Rift Valley fever virus in mice.
Nature communications. 11(1) [DOI] 10.1038/s41467-020-17101-y. [PMID] 32612175.
2020
SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography
Nature Communications. 11(1) [DOI] 10.1038/s41467-020-19619-7. [PMID] 33208793.
2020
The origin of diarrhea in rotavirus infection.
Science (New York, N.Y.). 370(6519):909-910 [DOI] 10.1126/science.abf1914. [PMID] 33214264.
2019
Differential Regulation of Type I and Type III Interferon Signaling.
International journal of molecular sciences. 20(6) [DOI] 10.3390/ijms20061445. [PMID] 30901970.
2019
Hypoxic Environment Promotes Barrier Formation in Human Intestinal Epithelial Cells through Regulation of MicroRNA 320a Expression
Molecular and Cellular Biology. 39(14) [DOI] 10.1128/mcb.00553-18.
2019
Novel Chimeric Gene Therapy Vectors Based on Adeno-Associated Virus and Four Different Mammalian Bocaviruses.
Molecular therapy. Methods & clinical development. 12:202-222 [DOI] 10.1016/j.omtm.2019.01.003. [PMID] 30766894.
2019
Teratogenic Rubella Virus Alters the Endodermal Differentiation Capacity of Human Induced Pluripotent Stem Cells
Cells. 8(8) [DOI] 10.3390/cells8080870. [PMID] 31405163.
2019
TRIM69 Inhibits Vesicular Stomatitis Indiana Virus.
Journal of virology. 93(20) [DOI] 10.1128/JVI.00951-19. [PMID] 31375575.
2019
Type-Specific Crosstalk Modulates Interferon Signaling in Intestinal Epithelial Cells.
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research. 39(10):650-660 [DOI] 10.1089/jir.2019.0040. [PMID] 31199715.
2018
Differential induction of interferon stimulated genes between type I and type III interferons is independent of interferon receptor abundance.
PLoS pathogens. 14(11) [DOI] 10.1371/journal.ppat.1007420. [PMID] 30485383.
2018
Reversible Fusion Proteins as a Tool to Enhance Uptake of Virus-Functionalized LbL Microcarriers.
Biomacromolecules. 19(8):3212-3223 [DOI] 10.1021/acs.biomac.8b00360. [PMID] 29966082.
2018
Rubella Virus Strain-Associated Differences in the Induction of Oxidative Stress Are Independent of Their Interferon Activation.
Viruses. 10(10) [DOI] 10.3390/v10100540. [PMID] 30282907.
2017
Genome packaging of reovirus is mediated by the scaffolding property of the microtubule network.
Cellular microbiology. 19(12) [DOI] 10.1111/cmi.12765. [PMID] 28672089.
2017
Mechanism of membrane fusion induced by vesicular stomatitis virus G protein.
Proceedings of the National Academy of Sciences of the United States of America. 114(1):E28-E36 [DOI] 10.1073/pnas.1618883114. [PMID] 27974607.
2017
miR-16 and miR-125b are involved in barrier function dysregulation through the modulation of claudin-2 and cingulin expression in the jejunum in IBS with diarrhoea.
Gut. 66(9):1537-1538 [DOI] 10.1136/gutjnl-2016-311477. [PMID] 28082316.
2017
Reovirus inhibits interferon production by sequestering IRF3 into viral factories.
Scientific reports. 7(1) [DOI] 10.1038/s41598-017-11469-6. [PMID] 28883463.
2017
Type I and Type III Interferons Display Different Dependency on Mitogen-Activated Protein Kinases to Mount an Antiviral State in the Human Gut.
Frontiers in immunology. 8 [DOI] 10.3389/fimmu.2017.00459. [PMID] 28484457.
2016
Reovirus intermediate subviral particles constitute a strategy to infect intestinal epithelial cells by exploiting TGF-β dependent pro-survival signaling.
Cellular microbiology. 18(12):1831-1845 [DOI] 10.1111/cmi.12626. [PMID] 27279006.
2015
Dynamics of virus-receptor interactions in virus binding, signaling, and endocytosis.
Viruses. 7(6):2794-815 [DOI] 10.3390/v7062747. [PMID] 26043381.
2013
Arbidol inhibits viral entry by interfering with clathrin-dependent trafficking.
Antiviral research. 100(1):215-9 [DOI] 10.1016/j.antiviral.2013.08.008. [PMID] 23981392.
2013
Similar uptake but different trafficking and escape routes of reovirus virions and infectious subvirion particles imaged in polarized Madin-Darby canine kidney cells.
Molecular biology of the cell. 24(8):1196-207 [DOI] 10.1091/mbc.E12-12-0852. [PMID] 23427267.
2011
A recombinant vesicular stomatitis virus bearing a lethal mutation in the glycoprotein gene uncovers a second site suppressor that restores fusion.
Journal of virology. 85(16):8105-15 [DOI] 10.1128/JVI.00735-11. [PMID] 21680501.
2010
SV40 associated miRNAs are not detectable in mesotheliomas.
British journal of cancer. 103(6):885-8 [DOI] 10.1038/sj.bjc.6605848. [PMID] 20717113.
2009
Modulation of PML protein expression regulates JCV infection.
Virology. 390(2):279-88 [DOI] 10.1016/j.virol.2009.05.017. [PMID] 19523662.
2008
Direct correlation between sialic acid binding and infection of cells by two human polyomaviruses (JC virus and BK virus).
Journal of virology. 82(5):2560-4 [PMID] 18094176.
2008
Human alpha-defensins inhibit BK virus infection by aggregating virions and blocking binding to host cells.
The Journal of biological chemistry. 283(45):31125-32 [DOI] 10.1074/jbc.M805902200. [PMID] 18782756.
2007
Identification of amino acid residues in BK virus VP1 that are critical for viability and growth.
Journal of virology. 81(21):11798-808 [PMID] 17699578.
2006
JC virus minor capsid proteins Vp2 and Vp3 are essential for virus propagation.
Journal of virology. 80(21):10858-61 [PMID] 17041227.
2006
The human polyomaviruses.
Cellular and molecular life sciences : CMLS. 63(7-8):865-76 [PMID] 16501889.
2004
The human polyomavirus, JCV, uses serotonin receptors to infect cells.
Science (New York, N.Y.). 306(5700):1380-3 [PMID] 15550673.
Cellular polarity asymmetrically functionalizes pathogen recognition receptor-mediated intrinsic immune response in human intestinal epithelium cells
. [DOI] 10.1101/450668.
Correlative cryo-structured illumination fluorescence microscopy and soft X-ray tomography elucidates reovirus intracellular release pathway
. [DOI] 10.1101/2020.01.13.904623.
Functional comparison of MERS-coronavirus lineages reveals increased zoonotic potential of the recombinant lineage 5
. [DOI] 10.21203/rs.3.rs-38496/v1.
Host Cell Proteases Drive Early or Late SARS-CoV-2 Penetration
. [DOI] 10.1101/2020.12.22.423906.
SARS-CoV-2 structure and replication characterized byin situcryo-electron tomography
. [DOI] 10.1101/2020.06.23.167064.

Education

PhD Molecular Biology, Cell Biology and Biochemistry
2009 · Brown University
BSc Chemistry, minor Biology
2003 · Boston University

Contact Details

Phones:
Business:
(352) 273-7533
Emails:
Business:
m.stanifer@ufl.edu
Addresses:
Business Mailing:
PO Box 100266
GAINESVILLE FL 32610
Business Street:
ARB R1-273
1200 Newell Dr
Gainesville FL 32601