morphogenesis

A major focus of our lab is to understand how organs take their shapes. We seek to explore the genetic and signaling regulation that modulates cell behaviors and fates in order to generate correct tissue morphologies and cellular identities during development. One of our favourite subjects is the developing tooth, which begins its formation as a single layered epithelium and gradually undergoes a series of morphological changes, while interacting with the underlying mesenchyme. Our lab interrogates the genetic pathway, signaling control, and cell-cell adhesion that govern how this developing epithelium buckles, invaginates, turns, and forms in the appropriate size. While the tooth invaginates, several other craniofacial structures, such as the taste bud and the ear, bend upwards. We are fascinated by the developmental mechanisms that generate these morphological differences and we are employing techniques, such as single cell RNA-seq and live imaging in our studies.

stem cell biology in the epithelium

Once an organ is formed, it must also be maintained or repaired in order to function normally throughout the lifespan of the animal. Tissue regeneration is dependent on proper regulation of resident somatic stem cells, which first give rise to the highly-proliferative transit amplifying cells and then differentiated cells. Using the adult incisor epithelium as a model, we investigate mechanisms that control the transition between these different stages and the coordination between cell proliferation and differentiation. From the signaling and genetic pathways to the cellular movement and orientation, we take a multidisciplinary approach to understand stem cell regulation in teeth and other craniofacial structures, and ultimately apply this knowledge towards organ bioengineering and regenerative medicine.

biomechanics of tooth development & regeneration

As an embryo develops and primordial organs begin to take shape, a confluence of biochemical and mechanical signals instructs constituent cells to organize into specific patterns and forms. What are the functional roles of these mechanical signals and how are forces integrated with signaling pathways, such as Hippo and Integrin, to control morphogenesis? We collaborate with the research groups of Otger Campàs at UCSB and Ophir Klein at UCSF to use state-of-the-art biomechanical techniques to measure cellular and tissue forces during development, and combine that with mouse genetics and live imaging to investigate the mechanical regulation of organ shape acquisition.

We also study how tissue architecture and associated mechanics contribute to stem cell regulations in adult organs, focusing on understanding the roles of cell density, adhesion, and arrangement in governing epithelial cell proliferation and differentiation.