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. 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.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Development Center (PN2)
Project #
Application #
Study Section
Special Emphasis Panel (ZEY1-VSN (20))
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
Jin, Weiyang; Black, Charles T; Kam, Lance C et al. (2017) Probing Synaptic Biomechanics Using Micropillar Arrays. Methods Mol Biol 1584:333-346
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
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
Hu, Junqiang; Gondarenko, Alexander A; Dang, Alex P et al. (2016) High-Throughput Mechanobiology Screening Platform Using Micro- and Nanotopography. Nano Lett 16:2198-204
Raviram, Ramya; Rocha, Pedro P; Müller, Christian L et al. (2016) 4C-ker: A Method to Reproducibly Identify Genome-Wide Interactions Captured by 4C-Seq Experiments. PLoS Comput Biol 12:e1004780
Cai, Haogang; Wind, Shalom J (2016) Improved Glass Surface Passivation for Single-Molecule Nanoarrays. Langmuir 32:10034-10041
Meacci, Giovanni; Wolfenson, Haguy; Liu, Shuaimin et al. (2016) ?-Actinin links extracellular matrix rigidity-sensing contractile units with periodic cell-edge retractions. Mol Biol Cell 27:3471-3479
Schmid, Eva M; Bakalar, Matthew H; Choudhuri, Kaushik et al. (2016) Size-dependent protein segregation at membrane interfaces. Nat Phys 12:704-711

Showing the most recent 10 out of 158 publications