Research

Background

Cellular proliferation and differentiation needs to be tightly regulated to maintain tissue mass and homeostasis and if this regulation is lost cellular overgrowth and cancer occurs. In addition, this regulation also needs to be dynamically regulated throughout development and in regenerative processes. In recent years the Hippo pathway has been elucidated as a potent regulator in these processes, where it functions as a nexus and signal integrator of diverse cellular signals. The core components of the Hippo pathway comprise a regulatory serine–threonine kinase module and a transcriptional module. Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are the major downstream effectors in this transcriptional module where they predominantly bind to and regulate the activity of the TEAD family of transcription factors. YAP/TAZ therefore coordinates regulation of stem cell proliferation and differentiation, and correct regulations of YAP/TAZ is therefore essential to maintain tissue mass and homeostasis.

Screenshot 2018-10-22 at 14.11.59

Overview

Recently, the understanding of the regulatory mechanisms of the Hippo pathway has become a major focus, especially in cancer biology and regenerative medicine. Understanding the chief biological output of the Hippo pathway centers on Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ), which are the prime mediators of the Hippo pathway. When they are active they shuttle to the nucleus and bind to and activate their cognate transcription factors. A wealth of cellular regulators have been identified, but how the dynamic subcellular regulation of the core players takes plays is not well understood. In addition we will seek to understand the biological role of the Hippo pathway in biological processes important for human health with a focus on regeneration, inflammation and cancer.

We utilize live cell and in vivo imaging in both mammalian cell culture and the Zebrafish in combination with genome editing, biochemistry, label free holographic imaging and gene expression analyses to address these questions.

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Collaborators

Prof. Gail McConnell https://www.strath.ac.uk/staff/mcconnellgailprof/ 

Dr. Pierre Bagnaninchi http://www.crm.ed.ac.uk/people/pierre-bagnaninchi

Prof. Brian Link: https://www.mcw.edu/departments/cell-biology-neurobiology-and-anatomy/faculty/brian-link-phd 

Dr. Tamir Chandra https://www.ed.ac.uk/mrc-human-genetics-unit/research/chandra-group

Dr. Binzhi Qian https://www.ed.ac.uk/centre-reproductive-health/dr-binzhi-qian

Dr. Yi Feng https://www.ed.ac.uk/inflammation-research/people/principal-investigators/dr-yi-feng

Dr. Sonja Vermeren https://www.ed.ac.uk/inflammation-research/people/principal-investigators/dr-sonja-vermeren

Prof. Donald Salter https://www.ed.ac.uk/pathology/people/staff-students/donald-salter