Megan L Stanifer

Megan L Stanifer,

Assistant Professor

Department: Molecular Genetics & Microbiology
Business Phone: (352) 273-7533
Business Email:

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)



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.
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.
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.
A Model for Network-Based Identification and Pharmacological Targeting of Aberrant, Replication-Permissive Transcriptional Programs Induced by Viral Infection.
Research square. [DOI] 10.21203/ [PMID] 35132404.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Invasiveness of Escherichia coli Is Associated with an IncFII Plasmid
Pathogens. 10(12) [DOI] 10.3390/pathogens10121645. [PMID] 34959600.
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.
SARS‐CoV‐2 infection remodels the host protein thermal stability landscape
Molecular Systems Biology. 17(2) [DOI] 10.15252/msb.202010188. [PMID] 33590968.
Selective Janus kinase inhibition preserves interferon-λ–mediated antiviral responses
Science Immunology. 6(59) [DOI] 10.1126/sciimmunol.abd5318. [PMID] 33990378.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
The origin of diarrhea in rotavirus infection.
Science (New York, N.Y.). 370(6519):909-910 [DOI] 10.1126/science.abf1914. [PMID] 33214264.
Differential Regulation of Type I and Type III Interferon Signaling.
International journal of molecular sciences. 20(6) [DOI] 10.3390/ijms20061445. [PMID] 30901970.
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.
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.
Teratogenic Rubella Virus Alters the Endodermal Differentiation Capacity of Human Induced Pluripotent Stem Cells
Cells. 8(8) [DOI] 10.3390/cells8080870. [PMID] 31405163.
TRIM69 Inhibits Vesicular Stomatitis Indiana Virus.
Journal of virology. 93(20) [DOI] 10.1128/JVI.00951-19. [PMID] 31375575.
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.
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.
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.
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.
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.
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.
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.
Reovirus inhibits interferon production by sequestering IRF3 into viral factories.
Scientific reports. 7(1) [DOI] 10.1038/s41598-017-11469-6. [PMID] 28883463.
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.
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.
Dynamics of virus-receptor interactions in virus binding, signaling, and endocytosis.
Viruses. 7(6):2794-815 [DOI] 10.3390/v7062747. [PMID] 26043381.
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.
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.
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.
SV40 associated miRNAs are not detectable in mesotheliomas.
British journal of cancer. 103(6):885-8 [DOI] 10.1038/sj.bjc.6605848. [PMID] 20717113.
Modulation of PML protein expression regulates JCV infection.
Virology. 390(2):279-88 [DOI] 10.1016/j.virol.2009.05.017. [PMID] 19523662.
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.
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.
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.
JC virus minor capsid proteins Vp2 and Vp3 are essential for virus propagation.
Journal of virology. 80(21):10858-61 [PMID] 17041227.
The human polyomaviruses.
Cellular and molecular life sciences : CMLS. 63(7-8):865-76 [PMID] 16501889.
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/
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.


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

Contact Details

(352) 273-7533
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PO Box 100266
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ARB R1-273
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