Events
QB3 Webinar: Kyle Daniels, Stanford University. “Programmable Signaling Domains Drive T Cells and Macrophages to User-Defined Functional States”
As immune cells have emerged as powerful therapeutic vehicles, many technologies have been developed to control immune cell function. Technologies like over-expression (of natural or synthetic proteins) and gene knockout (or knockdown) can substantially increase immune cell therapeutic efficacy. However, few technologies exist to simultaneously tune multiple cell phenotypes. Here, we use synthetic receptors with programmable signaling domains to control CAR T cell survival, proliferation, differentiation, and cytotoxicity. The same synthetic receptors enable control of macrophage polarization and phagocytosis. We combine experiments and quantitative models to map signaling domain composition to cell function. The models enable rational design of new signaling domains that drive immune cells to desired cell states in which multiple phenotypes have been simultaneously co-optimized.
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About the Speaker
Kyle obtained his BS in Biochemistry from the University of Maryland College Park in 2010, conducting undergraduate research with Dr. Dorothy Beckett, PhD. He obtained his PhD in Biochemistry with a certificate in Structural Biology and Biophysics. His dissertation is titled “Kinetics of Coupled Binding and Conformational Change in Proteins and RNA” and was completed in the laboratory of Dr. Terrence G. Oas, PhD. Kyle performed postdoctoral training with Dr. Wendell A. Lim, PhD at UCSF studying how CAR T cell phenotype is encoded by modular signaling motifs within chimeric antigen receptors.
Kyle’s lab is interested in harnessing the principles of modularity to engineer receptors and gene circuits to control cell functions.
The lab uses synthetic biology, medium- and high-throughput screens, and machine learning to: (1) Engineer immune cells to achieve robust and durable responses against various cancer targets, (2) Coordinate behavior of multiple engineered cell types in cancer, autoimmune disease, and payload delivery, (3) Control survival, proliferation, and differentiation of hematopoietic stem cells (HSCs) and immune cells, and (4) Explore principles of modularity related to engineering receptors and gene circuits in mammalian cells.
