Areas of Interest
Dr. Clark’s laboratory is interested in the cell biology of the
T lymphocyte as at relates to autoimmune diseases. The immune
response in autoimmune diseases such as Multiple Sclerosis and
Rheumatoid Arthritis, as well as animal models for these
diseases are studied at the level of the T cell. T cell gene
usage, T cell function and activation, and T cell migration and
homing are studied using T cell cloning and molecular biological
approaches. The understanding of basic T cell function as it
relates to autoimmune mediated pathology is the overall goal of
this laboratory.
Lab Rotation Projects
#1 – New mouse models of the human autoimmune diseases,
Multiple Sclerosis and Lupus.
#2 – In vivo resistance to both regulatory T cells and TGF-
-mediated immunoregulation as a new model/mechanism in
autoimmune diseases.
#3 – Studies at the molecular and protein level to
characterize the interaction of the T cell activation signaling
pathway and the TGF- signaling pathway.
Selected References
Wohlfert, EA, Nichols, FC, Nevius, E, Clark, RB. PPARγ and
Immunoregulation: Enhancement of Regulatory T cells Through
PPARγ-Dependent and Independent Mechanisms. J Immunol. 2007 Apr
1;178: 4129-35.
Wohlfert EA and Clark, RB. Vive la Résistance!’– the PI3K–Akt
pathway can determine target sensitivity to regulatory T cell
suppression. Trends in Immunology 2007 Apr;28(4):154-60.
Wohlfert, EA, Gorelik, L, Mittler, R, Flavell, RA, Clark, RB.
Cutting Edge: Deficiency in the E3 Ubiquitin Ligase Cbl-b
Results in a Multifunctional Defect in T cell TGF-β Sensitivity
in Vitro and in Vivo. J. Immunol. 176: 1316-1320, 2006.
Wohlfert E, Callahan M, Clark RB: Resistance to CD4+CD25+
Regulatory T Cells and TGF-b in Cbl-b-/- Mice. J Immunol. 173:
1059-1065, 2004.
Clark RB. The role of PPARs in inflammation and immunity.
J Leukocyte
Biology 71:388-400, 2002.
Clark RB, Bishop-Bailey D, Estrada-Hernandez T, Hla T,
Puddington L, Padula SJ: The nuclear receptor PPARg and
immunoregulation. PPARg mediates inhibition of helper T cell
responses. J Immunol. 164:1364-1371, 2000.
Clark RB, Grunnet M, Lingenheld E: The generation of
encephalitogenic T cell lines from EAE-resistant strains of
mice. International Immunol. 9:1415-1422, 1997.
Barbarese E, Soares H, Yang S, Clark RB: Comparison of CNS
homing pattern among murine TH cell lines responsive to myelin
basic protein. J Neuroimmunol. 39:151?162, 1992.
Padula SJ, Lingenheld EG, Stabach PR, Chou CHJ, Kono DH,
Clark RB: Identification of encephalitogenic Vb-4? bearing T
cells in SJL mice. Further evidence for the V? region disease
hypothesis? J Immunol. 146(3):879?883, 1991.
Ruddle NH, Bergman CM, McGrath MK, Lingenheld EG, Grunnet
ML, Padula SJ, Clark RB: An antibody to lymphotoxin and tumor
necrosis factor prevents transfer of experimental allergic
encephalomyelitis. J Exp Med. 11972:1193?1200, 1990.
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