T lymphocytes play a major role in the generation of the host response against pathogens, control of autoimmune and inflammatory reactions and cancer surveillance. In physiological conditions, an effective T cell response occurs
in a microenvironment that facilitates the coordinated action of multiple regulatory mechanisms, including the interplay with some specific T cell subsets. In this context, emerging data reveal the critical role of two small T cell subpopulations: regulatory T cells (Tregs) and gamma-delta T cells. A
current major effort in our lab is to elucidate the cellular and molecular mechanisms involved in the activation of these two subsets and their contribution to the regulation of the immune response. To address these questions we are undertaking a similar strategy for both cell types: 1) to define the conditions that drive their maturation and function; 2) to analyze
specific signaling events engaged upon their activation; 3) to uncover the cellular and molecular mechanisms underlying their impaired activity in pathological conditions. Our research involves a broad range of cellular,
molecular, biochemical and imaging procedures performed largely in primary human cells but also in mouse models. The common long term goal is to develop rational strategies to manipulate deficient T cell function with the purpose to induce,
direct or restore the normal immune response. We have established fruitful collaborative efforts inside and outside the University of Kentucky to support our findings and to help us to provide a strong rationale for the design of novel therapeutic approaches.
Ellis,I.G.; Reneer,M.C.; Vélez-Ortega, A.C.; McCool, A.; Marti, F. Generation of induced Regulatory T Cells from primary human naïve and memory T Cells. Journal of Visualized Experiments. (In press).
Reneer,M.C.; Estes,DJ, Vélez-Ortega, A.C.; Norris, A.; Mayer, M., Marti, F. Peripherally induced human regulatory T cells uncouple Kv1.3 activation from TCR-associated signaling. European Journal of Immunology. 41(11):3170-5, 2011.
Lapinski,P,E.; Oliver, J.A.; Bodie, J.N.; Marti, F.; King, .P.D. The T-cell-specific adapter protein family: TSAd, ALX, and SH2D4A/SH2D4B. Immunological Reviews, 232(1):240-54, 2009.
Martí, F.; Garcia,G.G.; MacGregor,J.N.; Lapinski,P.E.; King,P.D. Essential role of the T-cell specific Adapter protein in the activation of LCK in peripheral T cells. Journal of Experimental Medicine, 203(2):281-7, 2006.
Blank, M.C.; Masuda,E.; Martí,F .; King,P.D.; Redecha,P.B.; Wurzburger,R.J.; Peterson, M.G.E.; Tanaka,S.; Pricop,L. Altered transcription of the human Fc?RIIB gene mediated by a promoter polymorphism and association with systemic lupus erythematosus . Human Genetics 117(2-3):220-7, 2005.
Martí, F .; King,P.D. The p95-100 kDa ligand of the T-cell specific Adapter (TSAd) protein Src-homology-2 (SH2) domain implicated in TSAd nuclear import is p97 Valosin-containing protein (VCP). Immunology Letters, 97(2): 235-245, 2005.
Drappa, J.; Kamen,L.A.; Chan,E.; Georgiev,M.; Ashany,D.; Martí,F .; King,P.D. Impaired T cell death and Lupus-like autoimmunity in T-cell specific Adapter Protein-deficient mice . Journal of Experimental Medicine, 198(5): 809-821, 2003.
Brentjens, R.J.; Latouche,J.B.; Santos,E.; Marti,F .; Gong,M.C.; Lyddane,C.; King,P.D.; Larson, S.; Weiss,M.; Rivière,I.; Sadelain,M. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15 . Nature Medicine, 9(3):279-286, 2003.
Martí, F.; Bertran,E.; Llucià,M.; Villén,E.; Peiró,M.; García,J.; Rueda,F. Platelet factor 4 induces human natural killer cells to synthesize and release interleukin-8. Journal of Leukocyte Biology, 72(3): 590-597, 2002.
Martí, F.; Post,N.H.; Chan,E.; King,P.D. A transcription function for the T-cell specific Adapter (TSAd) Protein in T cells: critical role of the TSAD SH2 domain . Journal of Experimental Medicine, 193(12): 1425-1430, 2001.
Martí, F.; Krause, A.; Dupont,B.; Sadelain,M.; King,P.D. Negative-feedback regulation of CD28 costimulation by a novel MAP-kinase phosphatase, MKP6 . Journal of Immunology, 1 66(1): 197-206, 2001.