Yoji Shimizu, Ph.D.
The generation of an antigen-specific immune response requires the coordinated interaction of the various cellular constituents of the immune system with each other and with components of the extracellular environment found in tissue. These adhesive events are critical to the efficient trafficking of lymphocytes through the body, the interaction of T lymphocytes with antigen-presenting cells that initiates and sustains T cell activation, and the influx of leukocytes into sites of inflammation. Dr. Shimizu's laboratory is investigating the intracellular signal transduction events that regulate the strength of these adhesive interactions and the functional significance of these molecular mechanisms of cell adhesion and migration on the ability of the immune system to respond to pathogens and tumors.
Specific areas of investigation projects include:
- Analysis of the biochemical signaling events by which the antigen-specific T cell receptor regulates the functional activity of integrins, a family of cell adhesion receptors that mediates the adhesion of cells to other cells and to extracellular matrix molecules
- Mechanisms of receptor “cross-talk” that regulate integrin function
- The function of adapter proteins in regulating T cell gene transcription and cytoskeletal reorganization
- Elucidation of pathways mediating the migration and retention of tumor-specific T cells into sites of tumor growth
- Analysis of the function of the lipid kinase p110gamma in regulating the inflammatory response and T cell-dependent immune responses to vaccinia virus
Dr. Shimizu’s laboratory combines molecular and biochemical approaches with genetic models in the mouse where the impact of altering signaling pathways on the generation of antigen-specific and tumor-specific immune responses can be assessed. The long-term objective is to provide the knowledge base necessary to specifically modulate the immune response by targeting these mechanisms of cell adhesion and migration.
- Cornell University, Ithaca, NY (1982), B.A. (Biological Sciences)
- University of Wisconsin, Madison, WI (1987), Ph.D. (Genetics)
- National Institutes of Health, Bethesda, MD (1990), Postdoctoral Training (Immunology)
- Director of Graduate Studies, University of Minnesota Medical School, Minneapolis, MN Microbiology, Immunology & Cancer Biology (MICaB) Ph.D. Graduate Program, 2004 - present
- Professor, University of Minnesota Medical School, Minneapolis, MN, Department of Laboratory Medicine and Pathology, 1999 - present
- Immunology program leader, University of Minnesota Cancer Center, Minneapolis, MN, 1996 - present
- Associate Professor, University of Minnesota Medical School, Minneapolis, MN, Department of Laboratory Medicine and Pathology, 1994 - 1999
- Harry Kay Chair in Biomedical Research, University of Minnesota Medical School, Minneapolis, MN, Department of Laboratory Medicine and Pathology, 1994 - present
- Assistant Professor , University of Michigan Medical School, Ann Arbor, MI, Department of Microbiology and Immunology, 1991 - 1994
- Damon Runyon-Walter Winchell Cancer Research Fund Postdoctoral Fellow in the laboratory of Dr. Stephen Shaw, Experimental Immunology Branch, NIH/NCI, Bethesda, MD, 1988 - 1990
- Intramural Research Training Award (IRTA) Fellow in the laboratory of Dr. Stephen Shaw, Experimental Immunology Branch, NIH/NCI, Bethesda, MD, 1987 - 1988
- NIH Predoctoral Trainee in the laboratory of Dr. Robert DeMars, Laboratory of Genetics, University of Wisconsin, Madison, WI, 1982 - 1987
- Elected to The Phi Beta Kappa Society, Theta of New York , Cornell University, 1981
- Graduated with distinction in all subjects, Cornell University, 1982
- Recipient of two year Postdoctoral Fellowship, American Cancer Society, Declined in favor of Damon Runyon Fellowship, 1988
- Recipient of Postdoctoral Fellowship for Basic Scientists (DRG-993), Damon Runyon-Walter Winchell Cancer Research Fund, 1988 - 1990
- Recipient of Junior Faculty Research Award, American Cancer Society, 1991
- Special Reviewer, Pathobiochemistry Study Section, February 1993, NIH, 1993
- Guest Reviewer, Pathology A Study Section, June 1995, NIH, 1995
- Member, Pathobiochemistry Study Section, NIH, 1995 - 1999
- Section Editor, Journal of Immunology, 1996 – 2001
- Chair, Autumn Immunology Conference, 1999
- Highly cited researcher in immunology, ISIHighlyCited.com, 2003
- DeNucci, C.C., Mitchell, J.S. and Shimizu, Y. 2009. Integrin function in T cell homing to lymphoid and non-lymphoid sites: getting there and staying there. Crit. Rev. Immunol. 29:87-109.
- Burbach, B.J., Srivastava, R., Medeiros, R.B., O'Gorman, W.E., Peterson, E.J. and Shimizu, Y. 2008. Distinct regulation of integrin-dependent T cell conjugate formation and NF-kB activation by the adapter protein ADAP. J. Immunol. 2008; 181:4840-4851.
- Nolz, J.C., Nacusi, L.P., Segovis, C.M., Medeiros, R.B., Mitchell, J.S., Shimizu, Y. and Billadeau, D.D 2008. The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL-C3G-mediated activated of Rap1. J. Cell Biol. 182:1231-1244.
- Thomas, M.S., Mitchell, J.S., DeNucci, C.C., Martin, A.L. and Shimizu, Y. 2008. The p110gamma isoform of phosphatidylinositol 3-kinase regulates migration of effector CD4 T lymphocytes into peripheral inflammatory sites. J. Leukoc. Biol. 84:814-823.
- Martin, A.L., Schwartz, M.D., Jameson, S.C. and Shimizu, Y. 2008. Selective regulation of CD8 effector T cell migration by the p110gamma isoform of phosphatidylinositol 3-kinase (PI 3-K). J. Immunol.180:2081-2088.
- Mueller, K.L., Thomas, M.S., Burbach, B.J., Peterson, E.J. and Shimizu, Y. 2007. Adhesion and degranulation-promoting adapter protein (ADAP) positively regulates T cell sensitivity to antigen and T cell survival. J. Immunol. 179:3559-3569.
- Nolz, J.C., Medeiros, R.B., Mitchell, J.S., Zhu, P., Freedman, B.D., Shimizu, Y. and Billadeau, D.D. 2007. WAVE2 recruits vinculin and talin to generate high affinity integrin binding at the immunological synapse. Mol. Cell. Biol. 27:5986-6000.
- Burbach, B.J., Medeiros, R.B., Mueller, K.L. and Shimizu, Y. 2007. T cell receptor signaling to integrins. Immunol. Rev. 218:65-81.
- Fischer, U.B., Jacovetty, E.L., Medeiros, R.B., Goudy, B.D., Zell, T., Swanson, J.-B., Lorez, E., Shimizu, Y., Miller, M.J., Khoruts, A. and Ingulli, E. 2007. MHC class II deprivation impairs CD4 T cell motility and responsiveness to antigen-bearing dendritic cells in vivo. Proc. Natl. Acad. Sci. USA 104:7181-7186.
- Gomez, T.S., Kumar, K., Medeiros, R.B., Shimizu, Y., Leibson, P.J. and Billadeau, D.D. 2007. Formins regulate the actin-related protein 2/3 complex-independent polarization of the centrosome to the immunological synapse. Immunity 26:177-190.
- Medeiros, R.B., Burbach, B.J., Mueller, K.L., Srivastava, R., Moon, J.J., Highfill, S., Peterson, E.J. and Shimizu, Y. 2007. Regulation of NF-kappaB activation in T cells via association of the adapter proteins ADAP and CARMA1. Science 316:754-758.
- George, T.C., Fanning, S.L., Fitzgerald-Bocarsly, P., Medeiros, R.B., Highfill, S., Shimizu, Y., Hall, B.E., Frost, K., Basiji, D., Ortyn, W.E., Morrissey, P.J. and Lynch, D.H. 2006. Quantitative measurement of nuclear translocation events using similarity analysis of multispectral cellular images obtained in flow. J. Immunol. Methods; 311:117-129.
- Nolz, J.C., Gomez, T.S., Zhu, P., Li, S., Medeiros, R.B., Shimizu, Y., Burkhardt, J.K., Freedman, B.D. and Billadeau, D.D. 2006. WAVE2 regulates actin cytoskeletal reorganization and CRAC-mediated calcium entry during T cell activation. Curr. Biol. 16:24-34.
- Finkelstein, L.D., Shimizu, Y. and Schwartzberg, P.L. 2005. Tec kinases regulate T cell receptor-mediated recruitment of signaling molecules and integrin-dependent cell adhesion. J. Immunol. 175:5923-5930.
- Rosenthal-Allieri, M.A., Ticchioni, M., Breittmayer, J.P., Shimizu, Y. and Bernard, A. 2005. Influence of beta1 integrin intracytoplasmic domains in the regulation of VLA-4-mediated adhesion of human T cells to VCAM-1 under flow conditions. J. Immunol. 175:1214-1223.
- Medeiros, R.B., Dickey, D.M., Chung, H., Quale, A.C., Nagarajan, L.R., Billadeau, D.B. and Shimizu, Y. 2005. Protein kinase D1 and the beta1 integrin cytoplasmic domain control beta1 integrin function via regulation of Rap1 activation. Immunity 23:213-226.
- Invited speaker, Department of Microbiology and Immunology 100th Anniversary Celebration, University of Michigan, Ann Arbor, MI, May 16-17, 2003. Presentation entitled “Integrins and the immune response.”
- Invited speaker, South Dakota Health Research Foundation/University of South Dakota, Sioux Falls, SD, October 23, 2003. Presentation entitled “Integrins and T lymphocyte function”.
- Invited speaker, Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, November 4, 2004.
- Invited speaker, Department of Immunology, Mayo Clinic, Rochester, MN, December 8, 2005. Presentation entitled “Making T cells stick: T cell receptor signal transduction and integrin activation”.
- Invited speaker, Experimental Immunology Branch, National Cancer Institute/National Institutes of Health, Bethesda, MD, April 24, 2006. Presentation entitled “T cell receptor signal transduction and integrin activation: molecular events downstream of protein kinase C”.
- Invited speaker, Seminars in Medicine, University of Minnesota-Duluth, Duluth, MN, November 7, 2006. Presentation entitled “Cell adhesion in the immune system: the role of adapter proteins in controlling T cell integrins”.
- Invited speaker, Center for Immunology, University of California-Irvine, Irvine, CA, November 29, 2007. Presentation entitled “Adapter proteins: linking the T cell receptor to integrins and beyond”.
- Invited speaker, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada, March 20, 2008. Presentation entitled “Regulation of integrin function and T cell activation by adapter proteins”.
- Invited speaker, 56th Annual Symposium on Fundamental Cancer Research, M.D. Anderson Cancer Center, Houston, TX, October 14-17, 2003. Presentation entitled “Lymphocyte adhesion, signal transduction and the immune response”.
- Invited discussion leader, Careers in Immunology Workshop, Autumn Immunology Conference, Chicago, IL, November 23, 2003 (declined due to scheduling conflict).
- Medeiros, R.B., Dickey, D.M., Chung, H., Quale, A.C., Nagarajan, L.R., Billadeau, D.D. and Shimizu, Y.: Protein kinase D and the beta1 integrin cytoplasmic domain coordinately control beta1 integrin function and clustering via regulation of Rap1 activation and membrane localization. Gordon Conference on Immunochemistry and Immunobiology, August 7-12, 2005. Invited oral presentation.
- Block symposia chair, Signal pathways in T cell development, regulation, and activation, American Association of Immunologists Annual Meeting, Boston, MA, May 12-16, 2006.
- Medeiros, R.B., Burbach, B.J., Mueller, K.L., Highfill, S., Peterson, E.J. and Shimizu, Y.: A novel function for ADAP in NF-kappaB activation downstream of PKC. 2006 AAI Annual Meeting, May 12-16, 2006. Oral presentation.
- Invited speaker, Gordon Conference on Fibronectin, Integrins and Related Molecules, Il Ciocco, Italy, April 22-27, 2007. Presentation entitled “Integrins, adapter proteins and T lymphocyte function”.