Yoji Shimizu, PhD

Professor, Department of Laboratory Medicine and Pathology

Yoji Shimizu

Contact Info

shimi002@umn.edu

Office Phone 612-626-6849

Lab Phone 612-626-6713

PhD, University of Wisconsin, Madison (Genetics), 1987

Bachelors Degree, Cornell University, Ithaca, NY (Biological Sciences), 1982

Summary

Dr. Shimizu is focused on trying to understand how immune responses are generated and how that information can be used in the clinic to improve patient care. He and his colleagues are particularly interested in identifying the general principles by which the T-cell response is initiated. These cells require contact with other cells order to become activated and play their role in an antigen-specific immune response. Cellular adhesion processes and cell-surface receptors transmit biochemical signals inside the cells that lead to T-cell activation and differentiation into cytotoxic T cells or helper T cells. Cellular adhesion spurs efficient trafficking of lymphocytes through the body and their influx to inflammatory sites. Shimizu’s laboratory is investigating the signaling pathways that regulate the strength of these adhesive interactions. His team is also exploring the functional significance of these T-cell molecular mechanisms and their role in the ability of the immune system to respond to pathogens and tumors.

Awards & Recognition

  • 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
  • U of MN Alumni Association 2011-12 Postbaccalureate, Graduate and Professional Education Award

Research

Research Summary/Interests

Shimizu has a long-standing and continuing research interest in the role of integrins in T-cell adhesion and activation. The integrins are a superfamily of cell adhesion receptors that T-cells use to carry out many of their normal functions, including their ability to migrate to sites in the body where they are needed. Shimizu and his University colleagues have identified novel signaling intermediates that promote integrin function and T-cell activation, and are currently investigating the role of integrins in controlling the localization of T-cells to specific anatomic sites in the body. Of particular interest is the tumor microenvironment, which is normally immunosuppressive and thus dampens the ability of T-cells to recognize and kill tumor cells. Sophisticated imaging technologies such as two-photon microscopy now make it possible to track the movement and behavior of T-cells in the normal and tumor tissue microenvironments. Currently, Shimizu and colleagues are using this technology to analyze the behavior of cytotoxic T-cells in the tumor microenvironment and the role of integrins and immune checkpoint blockade in controlling T-cell movement and retention in the tumor microenvironment.

Publications

  • Mitchell, J.S., Burbach, B.J., Srivastava, R., Fife, B.T. and Shimizu, Y.: Multi-stage T cell-dendritic cell interactions control optimal CD4 T cell activation through the ADAP-SKAP55 signaling module. J. Immunol. 2013; 191:2372-2383. PMCID: PMC3772631.
  • Zumwalde, N.A., Domae, E., Mescher, M.F. and Shimizu, Y.: ICAM-1 dependent homotypic aggregates regulate CD8 T cell effector function and differentiation during T cell activation. J. Immunol. 2013; 191:3681-3693. PMCID: PMC3803108.
  • Srivastava, R., Burbach, B.J., Mitchell, J.S., Pagan, A.J. and Shimizu, Y.: ADAP regulates cell cycle progression of T cells via control of cyclin E and cdk2 expression through distinct CARMA1-dependent signaling pathways. Mol. Cell. Biol. 2012; 32:1908-1917. PMCID: PMC3347422.