The overall goal of our lab is to try to understand the biochemical and molecular pathways involved in T cell tolerance. Our strategy is to take a genomic approach toward uncovering both known and novel genes contributing to this state. First we are employing microarray analysis of cDNA derived from T cell clones stimulated under various tolerizing and activating conditions. By utilizing sophisticated clustering and pattern analysis computer programs we are in the process of identifying the genes as well as the pathways involved in inducing and maintaining T cell tolerance. Once these genes/pathways are identified we are determining their functional role in both our in vitro and in vivo model systems. In addition to this "differential expression" approach we are also employing a "functional genomic" approach by transfecting T cell clones with libraries derived from tolerant cells and selecting for genes that either positively or negatively effect IL-2 promoter driven transcription. Finally, based on our T cell tolerance studies we have developed a stem cell transplantation model for treating mice transgenic for sickle hemoglobin and in the future hope to apply our findings to enhancing anti-tumor immunity in vivo.

Safford M, Collins, S, Lutz, M, Allen, A, Huang CT, Kowalski J, Blackford A, Horton M, Drake CG, Schwartz RH, Powell JD. (2005) Egr-2 and Egr-3 are negative regulators of T cell activation. Nat. Immunol. 3(7):627-34 [PubMed]

Kowalski J., Drake C., Schwartz RH, and Powell J. (2004) Non-Parametric, Hypothesis-Based Analysis of Microarrays for Multiple Phenotype Comparisons with very few Samples. Bioinformatics 353: 167-170 [PubMed]

Allen A., Zheng Y, Gardner L, Safford M, Horton MR, Powell JD. (2004) The novel cyclophilin binding compound Sanglifehrin A disassociates G1 cell cycle arrest from tolerance induction. J. Immunol. 186 (8);1333-1345 [PubMed]

Powell JD, Boodoo S, Horton MR. (2004) Identification of the molecular mechanism by which TLR ligation and IFN-gamma synergize to induce MIG. Clin. Dev. Immunol. 95:7568-7573 [PubMed]

Kowalski J, Powell J. (2004) Nonparametric inference for stochastic linear hypotheses: Application to high-dimensional data. Biometrika 14, 135-143, Cover Article [PubMed]

Huang CT, Workman CJ, Flies D, Pan X, Marson AL, Zhou G, Hipkiss EL, Ravi S, Kowalski J, Levitsky HI, Powell JD, Pardoll DM, Drake CG, Vignali DA. (2004) Role of LAG-3 in regulatory T cells. Immunity 193(10):1113-21 [PubMed]

Sikder H, Huso DL, Zhang H, Wang B, Ryu B, Hwang ST, Powell, JD, Alani RM. (2003) Disruption of Id1 reveals major differences in angiogenesis between transplanted and autochthonous tumors. Cancer Cell 337: 274-276 [PubMed]

Shin T, Kennedy G, Gorski K, Tsuchiya H, Koseki H, Azuma M, Yagita H, Chen L, Powell J, Pardoll D, Housseau F. (2003) Cooperative B7-1/2 (CD80/CD86) and B7-DC Costimulation of CD4+ T Cells Independent of the PD-1 Receptor. J. Exp. Med. 370: 647-650 [PubMed]