Presenter Dr. Alex Vlahos
Dr. Alexander Vlahos completed his PhD in Biomedical Engineering with Dr. Michael Sefton at the University of Toronto. Using principles in tissue engineering, regenerative medicine, and biomaterials, he developed platforms to vascularize the subcutaneous space for islet transplantation in pre-clinical animal models. In addition, he developed a “bottom-up” approach to creating pseudo-islets constructs with tuneable properties using disaggregated islet cells, exogenous vascular support cells and a collagen scaffold. Following these accomplishments, he realized that any further improvement for cell transplantation would rely on the ability to program intercellular signalling for immune modulation. For his postdoctoral studies he transitioned to the field of mammalian synthetic biology with Xiaojing Gao at Stanford University. His long-term vision is to establish synthetic protein circuits as a platform to mechanistically study complex intercellular interactions of multicellular systems, such as the immune system. The ensuing
Abstract
Tissue engineering has shown promising therapeutic potential; however, the immune system remains a key barrier that must be overcome for long-term cellular engraftment. Current strategies focused on local immune modulation often generate acute responses, largely due to their inability to dynamically respond, or finite reservoir of immune-modulating biologics. In comparison, the field of synthetic biology is uniquely suited to provide the means for probing and controlling such interactions using engineered cells with synthetic circuits that can respond to combinatorial environmental inputs, interrogate natural systems, and produce controlled therapeutic responses. An effective approach for programming cellular behavior involves the use of synthetic protein circuits, however, these circuits are limited to cytosolic proteins and achieving immune modulation requires the ability to control intercellular signalling.
To overcome these challenges, I developed a generalizable platform called RELEASE to enable synthetic protein circuits to control intercellular signaling. I then expanded the programming capabilities of RELEASE, while minimizing the overall genetic payload for engineering mammalian cells. In a separate project, I developed a high-throughput assay to determine key design principles of human transmembrane domains to guide the future engineering of synthetic protein tools and receptors. Through leveraging synthetic protein circuits, my vision is to engineer cells that interface with complex multicellular systems and identify essential signals to bias therapeutic responses, particularly in enhancing long-term cellular engraftment.
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