Dr. Donna Farber Research
The focus of Dr. Farber’s research is on immunological memory, and in particular on memory T cells which direct and coordinate anamnestic immune responses to pathogens and can mediate immunopathology in autoimmune disease and in transplantation. Memory T cells are generated following an initial encounter with antigen and can persist in multiple lymphoid and non-lymphoid peripheral tissue sites. We have recently identified that lungs contain a resident population of memory T cells that are retained in the lung and mediate optimal protective responses to influenza virus. We are investigating how these tissue resident memory T cells are generated and retained in mucosal sites in mouse virus infection models, and how pancreas-homing autoreactive memory T cells are generated and maintained in a mouse model for Type I diabetes. Biochemical and molecular approaches are also being taken to elucidate mechanisms controlling the rapid recall response of memory T cells and their homeostasis and maintenance in mouse models with conditional deletion of key signal transduction intermediates. We have recently begun translational studies on human memory T cells, with a focus on characterizing tissue-specific immune responses in multiple lymphoid and non-lymphoid human tissue obtained from organ donors in collaboration with the New York organ donor network. Other translational studies in progress include analyses of T cell homeostasis and function in human transplant recipients and in Type I diabetes.
Damian Turner, PhD
Masaru Kutoba, MD
Kara Bickham, MD
Minjin Yu, PhD
1. Tang, A.L., Bingaman, A.W., Kadavil, E.A., Leeser, D.B., and Farber, D.L. (2006) Generation and functional capacity of polyclonal alloantigen-specific memory CD4 T cells. Am. J. Transplant. 6:1275-1284. (editorial in the same issue by Fairchild, R., “Developing models to study the memory T cell barrier in transplantation”, 6:1246-1247)
2. Moulton, V., Bushar, N.D., Leeser, D., Patke, D.S. and Farber, D.L. (2006) Divergent generation of heterogeneous memory CD4 T cells. J. Immunol. 177: 869-876.
3. Ndejembi, M.P., Patke, D.S., Bingaman, A.W., Chandok, M.R., Azimzadeh, A., Nadler, S.G., and Farber, D.L. (2006) Control of Memory CD4 T cell recall by the CD28 costimulatory pathway. J. Immunol. 177: 7698-7706.
4. Chandok, M.R., Okoye, F.I., Ndejembi, M.P. and Farber, D.L. (2007) A biochemical signature for rapid recall of memory CD4 T cells. J. Immunol. 179:3689-3698.
5. Teijaro, J.R., Njau, M.P., Verhoeven, D., Chandran, S., Nadler, S.G., Hasday, J, and Farber, D.L. (2009) Costimulation modulation uncouples protection from immunopathology in memory T cell responses to influenza virus. J. Immunol. 182:6834-6843.
6. Sener, A., Tang, A.L. and Farber, D.L. (2009) Memory T cell predominance following T cell depletional therapy derives from homeostatic expansion of naive T cells. Am. J. Transplant. 9:2615-2623.
7. Chandran, S., Verhoeven, D., Teijaro, J.R., Fenton, M. and Farber, D.L. (2009) TLR2 engagement on DC promotes high frequency effector and memory CD4 T cell responses. J. Immunol. 183:7832-41.
8. Bushar, N.D., Corbo, E., Schmidt, M., Maltzman, J.S. and Farber, D.L. (2010) Ablation of SLP-76 signaling after T cell priming generates memory CD4 T cells impaired in steady-state and cytokine-driven homeostasis. Proc. Nat’l. Acad. Sci. U.S.A. 107:827-831.
9. Teijaro, J.R., Verhoeven, D., Page, C.A. and Farber, D.L. (2010) Memory CD4 T cells Direct Protective Responses to Influenza Virus in the Lung through Helper-independent Mechanisms. J. Virol. 84:9217-26. (selected for editors’ spotlight feature)
10. Lai, W., Yu, M., Okoye, F.I., Keegan, A.D. and Farber, D.L. (2011) Transcriptional control of rapid recall in Memory CD4 T cells. J. Immunol. 187: 133-40.