Kloe Keeter

UC San Francisco

“Investigating the effect of ligand signaling function on synthetic receptor activation”

We have recently reported a toolkit of synthetic adhesion molecules (syncams) that are responsible for cell migration, cell-cell binding, and cellular activation. We are therefore applying this synthetic adhesion toolkit to investigate how ligand intracellular signaling impacts synthetic Notch and CAR T cell activation.


We hypothesize that the intracellular domain features of a ligand, such as force applied by the target cell cytoskeleton, can increase the signaling response of synNotch and CAR receptors. Creating a toolkit of ten different synCAMs, with a constant extracellular domain and varied transmembrane / intracellular domains, will allow for a wide range of characterization of synCAMs effect on receptor function. We plan to express our entire toolkit in various cell types to see their effect on the two different receptors as well as see the effect of cell type on synCAMs effectiveness. By engineering interchangeable cells with precisely controlled and rewired adhesion functionality, this project will be able to characterize the importance of the intracellular domain. The current knowledge of extracellular domain properties is only part of the mechanism; the characterization of the intracellular domain properties will inform a full picture approach for future cell therapy treatments.

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