This week we profile a recent publication in Cell Reports from Dr. Xaralabos (Bob) Varelas’
(pictured, left) lab at Boston University with first author Dr. Julia Hicks-Berthet (right).
Can you provide a brief overview of your lab’s current research focus?
My lab has broad interests in understanding the signals that control stem cell self-renewal and differentiation. One of our primary focuses is defining signals that control stem cell activity in the lung epithelium. We have shown key roles for the Hippo pathway effectors YAP and TAZ in lung epithelial development and homeostasis. Our most recent publication in Cell Reports demonstrates essential roles for YAP and TAZ in maintaining lung epithelial homeostasis. The study explored roles for YAP and TAZ in adult lung epithelium and found that conditional deletion of theYap and Wwtr1/Taz genes in animal models led to severe lung damage that included alveolar and bronchial cellular defects. One notable phenotype that was further studied was an aberrant production of mucus secreting goblet cells that resulted from the transdifferentiation of airway club cells with low YAP/TAZ activity.
What is the significance of the findings in this publication?
Goblet cells secrete mucus that normally helps protect the lining of the bronchus and traps microorganisms for clearance. Aberrant specification of goblet cells contributes to defective lung functions that associate with a range of lung diseases (e.g. asthma, COPD, Cystic Fibrosis and chronic bronchitis). Identification of YAP/TAZ as key regulators of goblet cell production offers insight into molecular signals that may dysregulated in such diseases. Signals governing YAP/TAZ activity may offer a therapeutic means to restrict goblet cell production in disease.
What are the next steps for this research?
Several interesting questions arise from our study. One clinically relevant question is whether activation of YAP/TAZ in diseases that exhibit goblet cell expansion may reverse aberrant cell fate decisions that lead to high levels of mucus production. Better understanding the upstream signals that regulate YAP/TAZ activity in the lung epithelium would offer avenues for potential control of goblet cell differentiation in a therapeutic context.
Funding Sources:
