Graduate Student Seminar Series – Aaron Rosenstein

Graduate Student Seminar Series
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Location: TRI-UC (KITE) Basement Auditorium, 550 University Avenue
Presentation Title: FAST-STEM: A Human pluripotent stem cell engineering system toolkit for rapid design-build-test-learn development of human cell-based therapeutic devices
Abstract: Very recent clinical advances in stem cell derived tissue replacement and gene therapy, in addition to the rise of artificial intelligence-aided scientific discovery, have placed the possibility of rationally-designed human cell-based therapies firmly within reach. However, development of such cells and testing of their engineered gene circuit components, has proven highly challenging, due to the need for generating stable cell lines for each design–build–test–learn engineering cycle. Current approaches to generating stable human induced pluripotent stem cell (hiPSC) lines are highly time-consuming and suffer from lack of control, poor integration efficiency, and limited functionality. Validation in clinically relevant stem cell derived tissues is also broadly lacking. Such drawbacks are prohibitive to repeatably conducting cutting-edge stem cell engineering with broad application within a realistic timescaleframe with broad application, and will not scale with the future of regenerative medicine. Such drawbacks are prohibitive to repeatably conducting cutting-edge stem cell engineering a realistic timescale with broad application, and will not scale with the future of regenerative medicine. We have developed FAST-STEM (Facile Accelerated Stem-cell Transgene integration with SynBio Tunable Engineering Modes), a hiPSC landing-padengineering platform that drastically reduces the time to engineer generate ‘differentiation ready’ stem cell lines from several weeks to 7 days, exhibiting a ~612-fold improvement in transgene integration rate over previous methodologies. Additional FAST-STEM innovations include: (i) rapid and highly efficient transgene integration; (ii) copy number control; (iii) simultaneous or consecutive integration of multiple gene cassettes; (iv) library screen capability. In addition to this unique functional versatility, platform transportability and broad use case for stem cell-engineering was confirmed by differentiation into eight different cell types across nine different laboratories. This platform dramatically lowers the bar for integration of synthetic biology with regenerative medicine, enabling experiments which were previously deemed logistically impossible, thus and pavinges the way for sophisticated human cell device development.
Supervisor Name: Dr. Michael Garton
Year of Study: 4
Program of Study: PhD
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