Susan E. LaFlamme, PhD

The LaFlamme lab’s expertise is cell biology with a specific interest in the functional significance of the interaction of cells with their extracellular environment, specifically components of the extracellular matrix through integrin receptors. There are currently two projects in the lab. The first focuses on understanding mechanisms that regulate epithelial differentiation, employing the murine salivary gland as a model. Salivary glands contain multiple cell types, including acinar cells that produce saliva and myoepithelial cells which produce the contractile force to promote the secretion of saliva. Although both acinar and myoepithelial cells are critical to salivary gland function, the signaling mechanisms that drive differentiation of these two cell types remains unclear. Understanding these underlying mechanisms is important both from a basic cell biology and a tissue regeneration prospective. The latter is relevant to the salivary gland in particular, as irreversible damage to saliva producing acinar cells, as well as myoepithelial cells often occurs following radiation treatment for head and neck cancers. The lab has established a salivary gland epithelial cell line that exhibits phenotypic plasticity and can be induced to differentiate towards either pro-acinar or myoepithelial lineages when culture as spheroids. The lab is using these cells as a discovery tool together with mouse genetic models to dissect signaling pathways and niche factors that regulate acinar and myoepithelial cell fate decisions. Our recent studies demonstrate that the transcriptional co-activator TAZ and the ser/thr kinase RSK2 are critical regulators of the phenotype switch between pro-acinar and myoepithelial cell fates and suggest a role for laminin-binding integrins in the activation of TAZ and RSK2. The current focus is understanding the mechanisms regulating the activation of TAZ and RSK2 and identifying the downstream targets involved in regulating these cell fate decisions. The second project in the lab focuses on understanding the role of integrin-laminin interactions in regulating endothelial tube morphogenesis and stability, which is important step in the formation of new vessels in a process known as angiogenesis. Angiogenesis contributes to both normal and pathological processes, including tissue repair, cancer progression, and inflammation. It is a multistep process that involves the sprouting of new vessels from the preexisting vasculature, which then anastomose with neighboring sprouts to form new vascular networks. To study the contribution of integrin-laminin interactions to this process, the LaFlamme lab uses two organotypic co-culture angiogenesis assays. Using these assays, the lab recently demonstrated that two endothelial laminins, laminin-411 and laminin-511 regulate the formation of endothelial tubes and that the α6 laminin-binding integrins regulate the expression of  CXCR4 and laminin-511 to promote the formation and maintenance of endothelial tube morphology (Xu, 2019). These organotypic models together with mouse genetic models will be used to further characterize the mechanisms by which integrin-laminin interactions regulate these processes focusing on integrin-regulated signaling and gene expression.