The goals of our center are to 1) elucidate the mechanical biology of T cells 2) use this understanding of T cell mechanical biology to develop novel T cell culture systems'and engineered T cells for improved therapeutics. Adopfive immunotherapy overcomes many obstacles that limit vaccine strategies, by adoptively transferring T cells with controlled anfigenic specificity. In addifion, ex vivo culture of T cells allows for the generation of large numbers of T cells, which is of utmost importance in the face of T cell deficiencies in cancer. A major current challenge in adopfive immunotherapy is to control self-renewal potential of T cell, often referred to in immunology as 'memory', as it allows the immune system to maintain a higher frequency of T cells specific for pathogens encountered eariier. Another issue is self-renewal capacity in effector populafions such as Th17 CD4 cells that are high effecfive in adoptive immunotherapy models. Hence, by engineering this property into T cells used in adopfive immunotherapy, both the immediate and long-term effects of therapy could be improved. Our NDC hypothesized that the IS integrates chemical and mechanical signals to determine the course of T cell differentiafion. A major goal of our center is thus to improve immunotherapy by controlling the phenotype and funcfion of ex vivo expanded T cells and in scalable numbers. We will focus on immunotherapy of cancers including both leukemias and solid tumors. Besides using adoptive immunotherapy to selectively and directly attack the tumor or tumor stroma, immunotherapy can be used to protect the patient from immunopathology resulting from treatment efforts. During treatment of leukemia by hematopoietic cell transplant (HCT), which aims at reconstituting the recipient with hematopoietic and immune cells post chemotherapy, donor T cells can cause graft-versus-host-disease (GVHD) - a significant source of morbidity and mortality post-HCT. Current approaches to prevent GVHD, which rely on the use of convenfional drugs, and often lead to immunodeficiency, are not safisfactory and new GVHD preventive approaches are cleariy needed. Therefore, within our goal of improving pafient survival and quality of life, we also plan to make use of regulatory T cells (Tregs) to protect pafients from the GVHD toxic effect by modulating Treg funcfion and potency.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Development Center (PN2)
Project #
2PN2EY016586-07
Application #
8125678
Study Section
Special Emphasis Panel (ZEY1-VSN (20))
Program Officer
Fisher, Richard S
Project Start
2004-09-30
Project End
2015-07-31
Budget Start
2010-09-30
Budget End
2011-07-31
Support Year
7
Fiscal Year
2010
Total Cost
$3,919,500
Indirect Cost
Name
New York University
Department
Pathology
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Cai, Haogang; Muller, James; Depoil, David et al. (2018) Full control of ligand positioning reveals spatial thresholds for T cell receptor triggering. Nat Nanotechnol 13:610-617
Mayya, Viveka; Judokusumo, Edward; Abu Shah, Enas et al. (2018) Durable Interactions of T Cells with T Cell Receptor Stimuli in the Absence of a Stable Immunological Synapse. Cell Rep 22:340-349
Tipton, Laura; Müller, Christian L; Kurtz, Zachary D et al. (2018) Fungi stabilize connectivity in the lung and skin microbial ecosystems. Microbiome 6:12
Jin, Weiyang; Black, Charles T; Kam, Lance C et al. (2017) Probing Synaptic Biomechanics Using Micropillar Arrays. Methods Mol Biol 1584:333-346
Biggs, Manus J P; Fernandez, Marc; Thomas, Dilip et al. (2017) The Functional Response of Mesenchymal Stem Cells to Electron-Beam Patterned Elastomeric Surfaces Presenting Micrometer to Nanoscale Heterogeneous Rigidity. Adv Mater 29:
Lambert, Lester H; Goebrecht, Geraldine K E; De Leo, Sarah E et al. (2017) Improving T Cell Expansion with a Soft Touch. Nano Lett 17:821-826
Schmid, Eva M; Bakalar, Matthew H; Choudhuri, Kaushik et al. (2016) Size-dependent protein segregation at membrane interfaces. Nat Phys 12:704-711
Basu, Roshni; Whitlock, Benjamin M; Husson, Julien et al. (2016) Cytotoxic T Cells Use Mechanical Force to Potentiate Target Cell Killing. Cell 165:100-110
Cai, Haogang; Wolfenson, Haguy; Depoil, David et al. (2016) Molecular Occupancy of Nanodot Arrays. ACS Nano 10:4173-83
Baugh, Evan H; Simmons-Edler, Riley; Müller, Christian L et al. (2016) Robust classification of protein variation using structural modelling and large-scale data integration. Nucleic Acids Res 44:2501-13

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