Michael Gale
University of Minnesota, MN·Microbiology & Immunology
When a virus meets a new host, the first thing it runs into is innate immunity: the fast, built-in alarm system that every cell uses to detect infection and shut it down before antibodies or T cells arrive. How strong that barrier is varies from species to species and from virus to virus, and it helps decide whether a virus stays in bats, birds or rodents or spills over into people.
- Fields
Microbiology & Immunology
Genetics
Neuroscience
- Topics
innate immunity
interferon
flavivirus
- Grants
- 5 known grants, through May 2031
What they work on
- Test how interferon-driven antiviral defenses differ between mammalian species, using model alphaviruses and flaviviruses and comparative analyses that pinpoint which stage of the viral life cycle each species' response blocks.
- Determine which viral proteins let a virus evade innate immunity in a given host species, and use these virus-species pairings to assess each species' potential as a source of human infection.
- Build and publicly release annotated genomes and transcriptomes from a 'fibroblast zoo' of primary cells spanning diverse mammals, filling a gap that currently blocks comparative studies of virus control.
- Develop computational and statistical models, including machine learning for viral ecology, that predict which host and virus features determine replication success across species.
- Identify the cells that launch the immune response to West Nile virus outside the nervous system and the cytokine targets that keep the virus from invading the brain, using new mouse models and recombinant viral strains.
- Map the signaling circuits that start and spread inflammation inside the central nervous system during West Nile virus infection, using single-cell and spatial transcriptomic and epigenomic sequencing.
- Track brain cells that survive West Nile infection by using a recombinant virus expressing Cre recombinase to permanently label them, and test their contribution to inflammation persisting after the virus is cleared.
- Define how interleukin-15, an immune signaling protein linked to vaccine protection, reprograms monocytes and T cells, using in vitro and ex vivo rhesus macaque cell models.
- Validate the whole-blood transcriptomic signature that predicts protection from the RhCMV/SIV vaccine by testing it in an independent macaque vaccination and SIV-challenge cohort with bulk RNA-seq, scRNA-seq/CITE-seq and spatial tissue profiling.
More about the research
Work in this group traces that decision at the molecular level, across three fronts: how innate immune signaling differs among mammals and limits cross-species infection, how a mosquito-borne virus breaches the brain and leaves lasting inflammation behind, and how a highly protective experimental vaccine reprograms the immune system, read out through large-scale gene-expression profiling.
Why it matters
Knowing which innate immune defenses block a virus in which animal could help predict and disrupt the spillover of new viruses into people. For West Nile virus, which has caused tens of thousands of hospitalizations in the US, a molecular account of how it enters the brain and why inflammation lingers could inform treatments for the lasting cognitive and motor effects survivors face. The vaccine studies aim to explain why a cytomegalovirus-vectored vaccine controls SIV so effectively, information meant to guide human phase I/II testing of the same concept against HIV.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Dennis Hartigan-O'Connor
University of California-Davis, CA·Microbiology & Immunology
Test whether partial-agonist IL-10 cytokines combined with mRNA vaccination can make HIV-specific T-cell responses unusually durable in macaques, including CXCR5+ follicular T cells that enter lymph-node sites where antibody-producing B cells mature.
Vijayakumar Velu
Emory University, GA·Microbiology & Immunology
Test how soluble IL-15/IL-15Rα-Fc, an immune-boosting cytokine complex, and galunisertib, a TGF-β pathway blocker, alone or combined, change T cell and natural killer cell subsets during chronic SIV infection in antiretroviral-treated rhesus macaques.
Cara Pager
University at Albany, NY·Microbiology & Immunology
Mutate conserved adenosine-rich patches in the Zika virus 3' untranslated region within an infectious clone and a luciferase reporter replicon, then measure effects on protein production, genome replication and viral fitness in mammalian and mosquito cells.
The school
University of Minnesota: 88 labs on PI Pages, $1.4B a year on research, 722 research doctorates a year.
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