Research in the Stowers Lab draws from mechanical engineering, materials science, cell- and molecular biology to make discoveries at the frontier of mechanobiology.
Tunable hydrogels for 3D cell culture
3D hydrogels have been widely used to encapsulate cells in an environment that is physical and chemically more representative of the 3D extracellular matrix. However, there is still room to improve on conventional hydrogels in order to incorporate more complex aspects of the ECM or to control particular aspects in space or time. We seek to design hydrogels to serve both purposes. We are particularly interested in incorporating stimuli-responsive elements into hydrogels to provide exquisite control of gel properties. For example, the ability to tune hydrogel crosslinking with light allows the user to control the stiffness of the matrix in both space and time. This capability opens the door for exploration of interesting questions, like do cells remember their prior environments, and if so, how?
Elucidating the ECM-Epigenome connection
Tumor cells frequently have not only genetic mutations but also misregulated epigenomes. Solid tumor ECM is generally much stiffer than the soft tissue in which the tumor develops, but many of the hallmarks of cancer are associated with enhanced matrix stiffness. We seek to elucidate how the epigenome is remodeled in response to matrix stiffness. We have shown that histone remodeling enzymes (HDACs) are required for stiffness-induced tumorigenic phenotypes to occur in breast epithelium. Further, chromatin accessibility is also altered in response to matrix stiffness. We aim to further elucidate this ECM-epigenome axis to identify the players in this pathway. We also seek to extend these findings from the cancer realm to stem cell biology in order to better understand and control differentiation.
Studying and directing stem cell fate decisions.
We explore how a stem cell's microenvironment contributes to its differentiation pathway. By developing and utilizing tunable hydrogels we can direct differentiation toward specific lineages or permit maintenance of stemness. Our lab explores the molecular mechanisms stem cells use to sense their microenvironment and ultimately alter their fate.