This week we profile a recent publication in Biochimica et Biophysica Acta from
Dr. Pamela Hoodless (back, third from left) at the Terry Fox Laboratory.
Can you provide a brief overview of your lab’s current research focus?
The Hoodless laboratory investigates the mechanisms underlying gene regulation in the heart and gastrointestinal tract in the developing mouse. Previous work identified that Hippo signalling plays a critical role in cell fate determination in the liver. This pathway is known to regulate cell proliferation and organ size, and disruptions in this pathway can cause extensive overgrowth in organs, including the liver. Despite this critical role, the downstream gene targets regulated by Hippo remain unknown.
What is the significance of the findings in this publication?
In our current study, we identified Errb2 (also known as Her2 in humans) as a direct target of the TEAD and YAP complex, the downstream transcriptional effector of Hippo signalling, in both mouse liver and a human liver cell line. As the ErbB family of receptor tyrosine kinases are a well-known regulator of cell proliferation, our finding provides a mechanism through which the TEAD/YAP complex can control cell proliferation and ultimately organ size. Furthermore, YAP can act as an oncogene, which is amplified or overexpressed in many cancer types including liver, suggesting this mechanism may contribute to cancer progression.
What are the next steps for this research?
Our ongoing research is exploring how these elements of the Hippo pathway interact with other transcription factors to control cell differentiation and proliferation in these systems.
This research was funded by:
This work is funded by CIHR and the Cancer Research Society.
