The Scientific Core (Core B), will coordinate the use of mAbs and Ig fusion proteins for studying the expression and function of TIM proteins in T cell activation and tolerance. These reagents will be an easily accessible means of addressing the functions of these important immunoregulatory pathways. The major goals of the Scientific Core are to generate novel reagents that facilitate the analysis of the expression and function of TIM family members and to serve as a repository for and provide existing reagents for the PPG Projects. The availability of large quantities of mAbs and Ig fusion proteins Is critical to the success of Projects 1-4. MAbs will be used to visualize the expression of TIM family members and as pathway agonists and antagonists. Ig fusion proteins will be used for expression, function, and signaling studies. In addition, Ig fusion proteins may serve as a means to specifically block receptor/ligand interactions. To accomplish these goals, the Scientific Core has two aims:
Specific Aim 1 : To generate novel monoclonal antibodies and Ig fusion proteins to study the function and expression of TIM family members.
Specific Aim 2 : To serve as a repository and maintain and produce existing and newly generated TIM mAbs and Ig fusion proteins for PPG investigators. The production of these critical reagents by a core not only will be time and cost efficient, but also provide standardized reagents that will facilitate comparison of data by Investigators in this PPG.
The TIM pathway regulates immune responses and is involved in the development of asthma and autoimmune diseases. Core B will make reagents to (1) see where TIMs are expressed;(2) block the pathway;(3) activate the pathway, thereby understanding how best to regulate the immune response.
|Morales-Kastresana, Aizea; Telford, Bill; Musich, Thomas A et al. (2017) Labeling Extracellular Vesicles for Nanoscale Flow Cytometry. Sci Rep 7:1878|
|Kamphorst, Alice O; Wieland, Andreas; Nasti, Tahseen et al. (2017) Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent. Science 355:1423-1427|
|Santiago, César; Mudgal, Gaurav; Reguera, Juan et al. (2017) Allosteric inhibition of aminopeptidase N functions related to tumor growth and virus infection. Sci Rep 7:46045|
|Foks, Amanda C; Engelbertsen, Daniel; Kuperwaser, Felicia et al. (2016) Blockade of Tim-1 and Tim-4 Enhances Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice. Arterioscler Thromb Vasc Biol 36:456-65|
|Kim, Hye Young; Umetsu, Dale T; Dekruyff, Rosemarie H (2016) Innate lymphoid cells in asthma: Will they take your breath away? Eur J Immunol 46:795-806|
|Brauner, Eran; Gunda, Viswanath; Vanden Borre, Pierre et al. (2016) Combining BRAF inhibitor and anti PD-L1 antibody dramatically improves tumor regression and anti tumor immunity in an immunocompetent murine model of anaplastic thyroid cancer. Oncotarget 7:17194-211|
|Mahoney, Kathleen M; Rennert, Paul D; Freeman, Gordon J (2015) Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov 14:561-84|
|Echbarthi, Meriem; Zonca, Manuela; Mellwig, Rachel et al. (2015) Distinct Trafficking of Cell Surface and Endosomal TIM-1 to the Immune Synapse. Traffic 16:1193-207|
|Mahoney, Kathleen M; Freeman, Gordon J; McDermott, David F (2015) The Next Immune-Checkpoint Inhibitors: PD-1/PD-L1 Blockade in Melanoma. Clin Ther 37:764-82|
|Xiao, Yanping; Yu, Sanhong; Zhu, Baogong et al. (2014) RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance. J Exp Med 211:943-59|
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