Department Affiliation: Primary: Oncology; Secondary: Pharmacology and Molecular Sciences
Degree: M.D., Ph.D., Emory University School of Medicine
Rank: Assistant Professor
Telephone Number: 410-502-7887
Fax Number: 410-614-9705
E-mail address: poweljo@jhmi.edu
School of Medicine Address: Room 443, Cancer Research Bldg., 1650 Orleans Street, Baltimore, MD 21231
Mechanisms of T cell activation and tolerance
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.
Representative Publications:
Other graduate programs in which Dr. Powell participates:
Immunology Graduate Program
Anti-Cancer Drug Development Program
Other graduate programs in which Dr. Powell participates:
Immunology Graduate Program
Anti-Cancer Drug Development Program
- Horton, M.R., Boodoo, S., and Powell, J.D. NF-kappa B activation mediates the cross-talk between extracellular matrix and interferon-gamma (IFN-gamma) leading to enhanced monokine induced by IFN-gamma (MIG) expression in macrophages, J Biol. Chem. 277:43757-62, 2002. Pub Med Reference
- Shin, T., Kennedy, G., Gorski, K., Tsuchiya, H., Koseki, H., Azuma, M., Yagita, H., Chen, L., Powell, J., Pardoll, D., and Housseau, F. Cooperative B7-1/2 (CD80/CD86) and B7-DC costimulation of CD4+ T cells independent of the PD-1 receptor, J. Exp. Med. 198:31-38, 2003. Pub Med Reference
- Kowalski, J., Drake, C., Schwartz, R.H., and Powell, J. Non-parametric, hypothesis-based analysis of microarrays for multiple phenotype comparisons with very few samples, Bioinformatics 20:364-373, 2004. Pub Med Reference
- Sikder, H., Huso, D.L., Zhang, H., Wang, B., Ryu, B., Hwang, S.T., Powell, J.D., and Alani, R.M. Disruption of ID1 reveals major differences in angiogenesis between transplanted and autochtonous tumors, Cancer Cell. 4:291-299, 2003. Pub Med Reference
- Allen, A., Zheng, Y., Gardner, L., Safford, M., Horton, M.R., and Powell, J.D. The novel cyclophilin binding compound Sanglifehrin A disassociates G1 cell cycle arrest from tolerance induction, J. Immunology 172:4797-4803, 2004. Pub Med Reference
- Powell, J.D., Boodoo, S., and Horton, M.R. Identification of the molecular mechanism by which TLR ligation and IFN-gamma synergize to induce MIG, Clin. Dev. Immunol. 11:77-85, 2004. Pub Med Reference
- Kowalski, J. and Powell, J. Nonparametric inference for stochastic linear hypotheses: Application to high-dimensional data, Biometrika 91:393-408, 2004. Pub Med Reference Not Available.
- Huang, C.T., Workman, C.J., Flies, D., Pan, X., Marson, A.L., Zhou, G., Hipkiss, E.L., Ravi, S., Kowalski, J., Levitsky, H.I., Powell, J.D., Pardoll, D.M., Drake, C.G., and Vignali, D.A. Role of LAG-3 in regulatory T cells, Immunity 21:503-513, 2004. Pub Med Reference
- Safford, M., Collins, S., Lutz, M., Allen, A., Huang, C.T., Kowalski, J., Blackford, A., Horton, M., Drake, C.G., Schwartz, R.H., and Powell, J.D. Egr-2 and Egr-3 are negative regulators of T cell activation, Nature Immunology 6:472-480, 2005. Pub Med Reference
