Thomas M. Yankee, Pharm.D., Ph.D.
Director, Inflammation & Immunity Module (I2, CORE 810)
Microbiology, Molecular Genetics and Immunology
Pharm.D., University of Illinois at Chicago, 1995
Ph.D., Purdue University, West Lafayette, Indiana, 1999
Office: 3004 Hixon | Lab: 3005 Wahl Hall West
913-588-2507 | email | lab website
T cell homeostasis is critical for maintaining the balance between immune competency, autoimmunity, and malignancy. Immune competency is dependent on the recognition of foreign antigens and the ability to proliferate and differentiate appropriately. However, there is a fine line between recognizing foreign antigens and responding to self-antigens, which leads to autoimmunity. Peripheral T cell malignancies comprise 10% to 12% of all lymphoid tumors. In addition, understanding T cell homeostasis will permit the introduction of novel therapies for bone marrow transplant patients. The ability of T cells to "sense" the environment, distinguish "self" from "non-self", and proliferate and die appropriately is critical to sustaining the balance between immune competency, autoimmunity, and malignancy. The research in my laboratory focuses on the signaling pathways that link the cellular environment to cell fate decisions.
Our research emphasizes the function of an adaptor protein critical for T cell signaling called Gads. We have developed a mouse line that lacks Gads expression (J. Immunol. 173: 1711) and found that Gads is critical for T cell development and homeostasis. Further, we observed that homeostasis in CD4 + T cells and CD8 + T cells are differentially regulated and Gads is particularly critical for CD4 + T cell homeostasis.
Currently, our work on Gads centers on three major areas. First, we are investigating of the role of Gads in T cell development. Gads -/- mice have multiple blocks in T cell development and we are seeking to understand the molecular basis for each defect. Second, we are investigating the role of Gads in the immune response to a variety of pathogens. Third, we are investigating novel Gads-associated proteins and exploring the function of Gads in signaling through the T cell antigen receptor as well as T cell co-receptors.
- Zeng, L, Dalheimer, S.L., and Yankee, T.M. (2007) Gads-/- mice reveal functionally distinct subsets of TCRbeta+CD4-CD8- double-negative thymocytes. J. Immunol. 179: 1013.
- Yankee, T.M. , Yun, T.J., Draves, K.E., Ganesh, K., Bevan M.J., Kaja, M.K., and Clark E.A. (2004) The Gads (GrpL) adaptor protein regulates T cell homeostasis. J. Immunol. 173: 1711.
- Yankee, T.M. and Clark E.A.B-cell antigen receptor. In: Encyclopedia or Biological Chemistry. Ed. Lennarz, W.J., and Lane, M.D., Academic Press/Elsevier Science, San Diego, CA, in press.
- Yankee, T.M. , Solow, S., Draves, K.E., and Clark, E.A. (2003) Expression of the Grb2-Related Protein of the Lymphoid System/Gads adapter protein in B cell subsets enhances B cell antigen receptor signaling through Mitogen-Activated Protein Kinase pathways. J. Immunol. 170:349-55.
- Hong, J.J., Yankee, T.M., Harrison, M.L., and Geahlen, R.L. (2002) Regulation of signaling in B cells through the phosphorylation of Syk on linker-region tyrosines. J. Biol. Chem. 277: 31703-14.
- Yankee, T.M. , Draves, K.E., Ewings, M.K., Clark, E.A., and Graves, J.D. (2001) CD95/Fas induces cleavage of the GrpL/Gads adaptor and desensitization of antigen receptor signaling. Proc. Natl. Acad. Sci., 98: 6789-93.
- Graves, J., Yankee, T.M., Draves, K., Clark, E., and Krebs, E. (2001) Caspases: A signal transduction perspective. In: Protein Modules in Cellular Signaling. ed. Heilmeyer, L. and Friedrich, P. IOS Press, Washington, D.C., 2001, p. 374-83.
- Ma, H., Yankee, T.M., Hu, J., Asai, D.J., Harrison, M.L., and Geahlen, R.L. (2001) Visualization of Syk-antigen receptor interactions using green fluorescent protein: Different roles for Syk and Lyn in the regulation of receptor capping and internalization. J. Immunol. 166: 1507-16.
- Yankee, T.M. and Clark, E.A. (2000) Signaling through the B cell antigen receptor in developing B cells. Rev. Immunogenet., 2: 185-03.
- Yankee, T.M. , Keshvara, L.M., Sawaskikosol, S., Harrison, M.L., and Geahlen, R.L. (1999) Inhibition of signaling through the B cell antigen receptor by the proto-oncogene product, c-Cbl, requires Syk tyrosine 317 and the c-Cbl phosphotyrosine-binding domain. J. Immunol. 163: 5827-35.
- Keshvara, L.M., Isaacson, C.C., Yankee, T.M., Sarac, R., Harrison, M.L., and Geahlen, R.L. (1998) Syk- and Lyn-Dependent phosphorylation of Syk on multiple tyrosines following B-cell activation includes a site that negatively regulates signaling. J. Immunol. 161: 5276-83.
May 08, 2013