In parallel with engineering approaches, we are working to develop a multi-scale understanding of the mechanisms governing stem cell fate, including physiochemical, genetic, and epigenetic regulation of self-renewal and differentiation, in order to inform the development of novel stem cell technologies.
Molecular Mechanisms Regulating Cell Fate Stem cell differentiation recapitulates many developmentally relevant signaling pathways active during early embryogenesis; therefore, understanding stem cell identity, including the physical, transcriptional and epigenetic characteristics unique to the pluripotent state and how such characteristics change during stem cell differentiation will enable approaches aimed to model mammalian embryonic development and efficiently direct the differentiation of stem cells. In addition, stem cells produce a variety of morphogenic factors that vary over the course of differentiation. We are applying genomic, proteomic and glycomic tools in order to temporally characterize the complex profile of molecules synthesized by stem cells actively undergoing morphogenesis. We anticipate that a more comprehensive understanding of stem cell identity and endogenous patterns of molecule expression will yield new strategies to direct cell phenotype and contribute directly to the development of regenerative stem cell molecular therapies.
Dynamics of 3D Stem Cell Differentiation - In parallel, studies are aimed to specifically characterize the dynamics of differentiation in 3D systems, including the spatial and temporal patterns that arise during endogenous and directed differentiation. Characterization of cellular interactions and heterogeneity arising within the context of differentiation are expected to inform engineering approaches to perturb local differentiation patterns, in order to develop complex, functional 3D stem cell-derived tissues. Moreover, studies aimed to understand morphogenesis and remodeling of the EB microenvironment may highlight biophysical and biochemical principles relevant to developmental biology.