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Yoji
Shimizu, Ph.D.
Professor
Department of Laboratory Medicine and Pathology
University of Wisconsin - Madison, 1987, Ph.D.
shimi002@tc.umn.edu
612-626-6849 - office
612-626-6713 - lab
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Research Interests:
Signal
transduction,
lymphocyte activation, cell adhesion and migration
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:
1) 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; 2) mechanisms of receptor “cross-talk”
that regulate integrin function; 3) the function of adapter
proteins in regulating T cell gene transcription and cytoskeletal
reorganization; 4) elucidation of pathways mediating the migration
and retention of tumor-specific T cells into sites of tumor
growth; and 5) 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.
Dr. Shimizu's lab: http://www.tc.umn.edu/~shimi002/
Cancer Biology Training Grant : http://www.cancer.umn.edu/outreach/cbtraininggrant.html
Selected Recent Publications:
- 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.
- Pribila, J.T., Itano, A.A., Mueller, K.L. and Shimizu,
Y. 2004. The alpha1beta1 and alphaEbeta7 integrins define
a subset of dendritic cells in peripheral lymph nodes with
unique adhesive and antigen uptake properties. J.
Immunol. 172:282-291.
- Mueller, K.L., Daniels, M.A., Felthauser, A., Kao, C.,
Jameson, S.C. and Shimizu, Y. 2004. Cutting edge: LFA-1
integrin-dependent T cell adhesion is regulated by both
Ag specificity and sensitivity. J.
Immunol. 173:2222-2226.
- Kellermann, S.-A., Dell, C.L., Hunt, S.W., III and Shimizu,
Y. 2002. Genetic analysis of integrin activation in T lymphocytes.
Immunol.
Rev. 186:172-188.
- Woods, M.L., Kivens, W.J., Adelsman, M.A., Qiu, Y., August,
A. and Shimizu, Y. 2001. A novel function for the Tec family
tyrosine kinase Itk in activation of beta1 integrins by
the T cell receptor. EMBO
J. 20:1232-1244.
- Woods, M.L. and Shimizu, Y. 2001. Signaling networks regulating
beta1 integrin-mediated adhesion of T lymphocytes to the
extracellular matrix. J.
Leukoc. Biol. 69:874-880.
- Ottoson, N.C., Pribila, J.T., Chan, A.S.H. and Shimizu,
Y. 2001. Cutting edge: T cell migration regulated by CXCR4
chemokine receptor signaling to ZAP-70 tyrosine kinase.
J.
Immunol. 167:1857-1861.
- Peterson, E.J., Woods, M.L., Dmowski, S.A., Derimanov,
G. Jordan, M.S., Wu, J.N., Myung, P.S., Liu, Q.-H., Pribila,
J.T., Freedman, B.S., Shimizu, Y. and Koretzky, G.A. 2001.
Coupling of the TCR to integrin activation by SLAP-130/Fyb.
Science
293:2263-2265.
- Hunter, A.J., Ottoson, N., Boerth, N., Koretzky, G.A.
and Shimizu, Y. 2000. Cutting edge: a novel function for
the SLAP-130 adapter protein in beta 1 integrin signaling
and T lymphocyte migration. J.
Immunol. 164:1143-1147.
- Epler, J.A., Liu, R., Chung, H., Ottoson, N.C. and Shimizu,
Y. 2000. Regulation of b1 integrin-mediated adhesion by
T cell receptor signaling involves ZAP-70 but differs from
signaling events that regulate transcriptional activity.
J.
Immunol. 165:4941-4949.
Last updated on: August 24, 2009
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