B. Abstract and Specific Aims 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. Adoptive immunotherapy overcomes many obstacles that limit vaccine strategies, by adoptively transferring T cells with controlled antigenic specificity. In addition, 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 adoptive 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 earlier. Another issue is self-renewal capacity in effector populations such as Th17 CD4 cells that are high effective in adoptive immunotherapy models. Hence, by engineering this property into T cells used in adoptive 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 differentiation. A major goal of our center is thus to improve immunotherapy by controlling the phenotype and function 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 conventional drugs, and often lead to immunodeficiency, are not satisfactory and new GVHD preventive approaches are clearly needed. Therefore, within our goal of improving patient survival and quality of life, we also plan to make use of regulatory T cells (Tregs) to protect patients from the GVHD toxic effect by modulating Treg function and potency.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Development Center (PN2)
Project #
Application #
Study Section
Special Emphasis Panel (ZEY1)
Program Officer
Fisher, Richard S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
New York University
Schools of Medicine
New York
United States
Zip Code
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
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
Cai, Haogang; Wind, Shalom J (2016) Improved Glass Surface Passivation for Single-Molecule Nanoarrays. Langmuir 32:10034-10041
Wolfenson, Haguy; Meacci, Giovanni; Liu, Shuaimin et al. (2016) Tropomyosin controls sarcomere-like contractions for rigidity sensing and suppressing growth on soft matrices. Nat Cell Biol 18:33-42

Showing the most recent 10 out of 165 publications