Wayne M. Yokoyama, M.D.
Sam J. Levin and Audrey Loew Levin Professor
Internal Medicine
Rheumatology
Pathology and Immunology
Immunology Program
Molecular Microbiology and Microbial Pathogenesis Program
314-362-9075 314-362-3554 314-362-6783 314-362-9257 8045 10058 Clinical Sciences Research Building yokoyama@wustl.edu
cancer, immunology, innate immunity, NK cells, tumor biology, virology Host innate immune responses to tumors and pathogens
Research Abstract:
As components of the innate immune system, natural killer (NK) cells help defend the host from pathogens and cancer while the adaptive immune system is being mustered. We are particularly interested in NK cell responses with respect to the “missing-self” hypothesis that originally postulated that NK cells are prevented from killing by normal expression of ubiquitously expressed major histocompatibility complex class I (MHC-I) molecules on targets. When MHC-I is down-regulated (“missing”), then NK cells attack. Over the years, we have identified and characterized germline-encoded NK cell receptors that help explain missing-self, including inhibitory receptors for MHC-I that block the function of NK cell activation receptors that in turn recognize other target cell surface ligands, including virus-encoded ligands. Moreover, we showed that the inhibitory receptors ironically have a second function in licensing or educating individual NK cells by recognition of self-MHC-I in the host. Licensing allows the NK cell to be functionally competent to be triggered by their activation receptors. Our current work includes use of CRISPR-Cas9 to develop mice expressing only one receptor on all NK cells, allowing definitive analysis of how these receptors guide innate immune and NK cell functions in host responses to tumors and viruses.
Our lab also works on translational human immune studies, particularly in autoimmunity and HIV. We also study immune responses to viruses, including a mouse virus that induces autoimmunity.Mentorship and Commitment to Diversity Statement:I have devoted my career to training the next generation of scientists as evidenced by my heavy involvement in the Immunology PhD program and being MSTP Director. In my lab, I guide trainees to become independent investigators by encouraging them to think outside of the box, rather than just follow my specific instructions. Moreover, I help each trainee develop career skills beyond the lab bench. Finally, I am committed to diversity in the biomedical workforce in my leadership roles and in my own lab. I am proud of my former trainees who are now in academic research and education, and in industry.
Selected Publications:
Piersma, S.J., Poursine-Laurent, J., Yang, L., Barber, G.N., Parikh, B.A., and Yokoyama, W.M. Virus infection is controlled by hematopoietic and stromal cell sensing of murine cytomegalovirus through STING. eLife 2020; 9:e56882. PMCID: PMC7413665Parikh, B.A., Bern, M.D., Piersma, S.J., Yang, L., Beckman, D.L., Poursine-Laurent, J., Plougastel Douglas, B., and Yokoyama, W.M. Control of viral infection by natural killer cell inhibitory receptors. Cell Reports 2020; 32:107969. PMCID: PMC7458139Yokoyama, W.M. (Ed.) Annual Review of Immunology Vol. 38, Annual Reviews, Inc., Palo Alto, 2020, 831 ppPark, E., Patel, S.J., Wang, Q., Andhey, P., Zaitsev, K., Porter, S., Hershey, M., Bern, M., Plougastel-Douglas, B., Collins, P., Colonna, M., Murphy, K.M., Oltz, E., Artyomov, M., Sibley, L.D., and Yokoyama, W.M. Toxoplasma gondii infection drives conversion of NK cells into ILC1-like cells. eLife 2019; 8:e47605. PMCID: PMC6703900Lauron, E.J., Yang, L., Harvey, I.B., Sojka, D.K., Williams, G.D., Paley, M.A., Bern, M.D., Park, E., Victorino, F., Boon, A.C.M., and Yokoyama, W.M. Viral MHCI inhibition evades tissue-resident memory CD8+ TRM responses and limits antigen-driven TRM formation. J Exp Med 2019; 216:117-132. PMCID:PMC6314518Bern, M.D., Parikh, B.A., Yang, L., Beckman, D.L., Poursine-Laurent, J., and Yokoyama, W.M. Inducible downregulation of MHC class I results in natural killer cell tolerance. J Exp Med 2019; 216:99-116. PMCID:PMC6314522
Last Updated: 4/8/2021 3:07:59 PM
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