center for systems

& synthetic biology

an NIGMS national systems biology center


Director receives Transformative Research Award on Redesigning T Cells

October 6, 2014

 Wendell Lim has been awarded a Transformative R01 Research Award, intended to support “exceptionally innovative and/or unconventional research projects that have the potential to create or overturn fundamental paradigms”.


Lim’s research proposal focuses on redesigning the T cell, using synthetic biology to engineer therapeutic cells. Engineered cells have the potential to serve as powerful "smart" therapeutic agents, but we lack a systematic framework for engineering cells to optimize their efficacy and minimize their adverse effects. For example, T cells expressing artificial tumor-directed receptors (Chimeric Antigen Receptors - CARs) have achieved unexpected success in treating certain leukemias. But the engineered cells lack the precision and control of native T cells: off-target cell killing as well as hyperactivation of the immune system lead to severe adverse effects in most patients. Achieving control over these engineered T cells remains a major challenge to making this a safe and reliable therapy that can be extended to a wider range of diseases. This award will support the effort to apply the approaches of synthetic biology to systematically engineer therapeutic immune cells with far more tailored and precisely controlled behaviors. Knowledge of cell signaling will be used to engineer modular switches and circuits that can be used to control these therapeutic cells.