Patrick Mitchell
University of Washington, WA·Microbiology & Immunology
How a cell recognizes that it has been invaded is a basic question in immunology. Rotaviruses are the main cause of severe dehydrating diarrhea, responsible for an estimated 2 million hospitalizations and more than 200,000 deaths each year in children under five.
- Fields
Microbiology & Immunology
Biochemistry
Medicine & Clinical Research
- Topics
rotavirus
inflammasome
pyroptosis
- Grants
- 1 known grant, through Jul 2028
What they work on
- Map the host and viral determinants required for rotavirus NSP1, a non-structural protein that suppresses interferon responses, to trigger activation of the human NLRP1 inflammasome.
- Test whether NLRP1 inflammasome activation by rotavirus depends on NSP1 recruiting Cullin-RING ubiquitin ligase complexes, the cellular machinery that tags proteins for degradation, using biochemistry and engineered viruses.
- Establish a physiological rotavirus infection model with genetically engineered human small-intestine enteroids skewed toward enteroendocrine cells, the only gut lining cells that express NLRP1, to ask whether they support viral replication.
More about the research
Understanding the interactions between these viruses and host cells matters for both host defense and better treatments, and this project examines a newly discovered form of immune detection triggered by a rotavirus protein.
Why it matters
Rotavirus still causes hundreds of thousands of childhood deaths annually from dehydrating diarrhea. Mapping how a viral protein inadvertently sets off the NLRP1 inflammasome could reveal why some rotavirus strains infect some species and tissues but not others, and the engineered human gut enteroid models and reagents built here would give the field tools for future work on rotavirus disease and on how cells detect infection generally.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Emily Troemel
University of California-San Diego, CA·Microbiology & Immunology
Determine where and how the RIG-I-like receptor DRH-1 promotes defense against Orsay virus in C. elegans intestinal epithelial cells, including how it senses viral replication and triggers the IPR.
Steven Baker
Loyola University Chicago, IL·Microbiology & Immunology
Determine whether the drop in the influenza NP protein, a core viral genome-packaging protein, caused by non-canonical ISG15 (ncISG15) reflects faster protein turnover, RNA turnover, or both.
Mary Estes
Baylor College of Medicine, TX·Microbiology & Immunology
Determine how human rotavirus and norovirus replication and immune responses in human intestinal organoids change with co-culture of the donor's own immune and nerve cells, co-infection with other pathogens, and commensal bacteria.
The school
University of Washington: 81 labs on PI Pages, $1.7B a year on research, 694 research doctorates a year.
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