Wayne Yokoyama
Washington University in St Louis, MO·Microbiology & Immunology
Natural killer (NK) cells are immune cells that can destroy virus-infected and cancerous cells without prior exposure. Their decisions depend on a balance between activating and inhibitory receptors on their surface.
- Fields
Microbiology & Immunology
Genetics
Medicine & Clinical Research
- Topics
natural killer cells
NK cells
Ly49 receptors
- Grants
- 3 known grants, through Aug 2029
What they work on
- Identify the effector mechanisms by which NK cells constrain immune checkpoint therapy in mouse tumor models, using NK cell depletion, NK-deficient mice and transfer of NK cells into tumors.
- Evaluate how the activating receptor NKG2D contributes to NK cell subversion of checkpoint therapy, and test whether a similar process occurs in human tumors using patient tumor databases.
- Study how Ly49 activating receptors other than Ly49H help NK cells respond to murine cytomegalovirus, using mice in which all Ly49s are removed and replaced by a single Ly49.
- Characterize NK cells whose inhibitory Ly49 receptors mediate MCMV control through licensing and missing-self detection, and how different Ly49 receptors interact during infection.
- Determine how Ly49 affinity for self-MHC-I shapes NK cell licensing, effector inhibition and missing-self responses, using Ly49 knockout and single-Ly49 knockin mice.
- Define how the Ly49 receptor repertoire is established on NK cells and whether inhibitory Ly49 signaling directly confers the licensed state.
More about the research
In mice, many of these receptors belong to the Ly49 family, which the applicant's laboratory discovered. Ly49s detect MHC class I (MHC-I), a molecule healthy cells display as a "self" tag. Three projects ask how NK cells avoid attacking healthy tissue, how they fight viral infection, and, unexpectedly, how they can work against cancer immunotherapy. Mice engineered in the lab, lacking all Ly49s or carrying just one Ly49 on every NK cell, tie the projects together.
Why it matters
Knowing how NK cells interfere with immune checkpoint therapy could guide new ways to modulate these cells and improve cancer immunotherapy for patients. Work on viral control may help explain why certain human KIR receptors and their MHC-I partners are linked to protection from viral infection. Studies of NK tolerance add basic understanding of how these potent killer cells avoid attacking healthy tissue.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Daniel Ram
University of Central Florida, FL·Microbiology & Immunology
Develop a gold nanoparticle platform that displays chosen peptides on HLA-E, a non-classical MHC class I molecule, to replace stressed cell lines as a reproducible and scalable peptide-presentation method.
Seth Pollack
Northwestern University, IL·Medicine & Clinical Research
Determine a safe and effective dose of B10G5, an antibody that neutralizes the tumor-shed immune-suppressing protein MIC, and test whether it activates NK cells within canine soft tissue sarcomas.
Susheela Tridandapani
Ohio State University, OH·Microbiology & Immunology
Determine how stimulating NOD2, an intracellular bacterial-fragment sensor, reshapes monocytes and CLL nurse-like macrophages, including loss of the inhibitory phosphatase SHIP1 and receptor CD31 and gain of the activating Fc receptor FcγRI.
The school
Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.
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