(6bo) Synthetic Approaches to Control Cell Fate and Function

Cells are complex and transformable machines. In addition to their homeostatic functions, they are capable of sensing and processing diverse biochemical and biophysical signals. Furthermore, isogenic cells are capable of transforming into a multitude of states, including diseased ones, each with distinct sets of active regulatory programs. To decode these complex cellular programs, synthetic approaches provide exquisite quantitative control of the spatiotemporal, physical, and chemical properties of both extra- and intra-cellular regulatory components. My research focuses on two complementary experimental approaches: 1) Engineering synthetic cellular microenvironments with defined spatiotemporal, physical, and chemical properties; 2) Engineering synthetic intracellular signal-transducing machineries that have unique input-output functions and can interface with complex, native regulatory systems such as chromatin and the actin cytoskeleton. The main applications of these synthetic approaches are to: 1) Quantitatively interrogate and control the cellular programs and machines that define distinct stem cell and disease states and their developmental or oncogenic transformations; 2) Elucidate molecular mechanisms underlying cell regulation, including chromatin dynamics and cellular mechanotransduction. My research takes advantage of methods from and collaborations with the fields of synthetic biology, systems biology, materials science and engineering, stem cell and cancer biology, and biophysics. Together this work may be applied to diverse areas in regenerative medicine, cancer biology, and eukaryotic cellular biotechnology.

Past and current work in these areas include: 1) Organic-inorganic surface chemistry (Keung et al 2005, 2007); 2) Biophysical control of neural and embryonic stem cell differentiation and proliferation (Keung et al 2009, 2010, 2011, 2012, 2013); 3) Synthetic, site-specific genome-targeting of chromatin factors to engineer cellular logic, spatial transcriptional regulation, and memory (Keung et al 2014).