Our Research focuses on studying the Hippo pathway and its role in driving tumour and regenerative niches. We strive to provide fundamental insights into the pathway and the biological processes that it regulates. We use interdisciplinary approaches, including new imaging modalities and collaboration with physicists, as well as a range of cellular and in vivo model systems to gain new insights. Currently we have ongoing projects on how the Hippo pathway integrates with the immune system, mechanotransduction and resistance to therapeutics. We also have a particular interest in plasma membrane invaginations termed caveolae, as we have recently shown a direct link between caveolae and the Hippo Pathway. In addition, we are identifying small molecule modulators of the Hippo pathway. Overall we strongly believe that understanding fundamental regulation at the molecular level is necessary to fully explore the therapeutic possibilities of targeting this pathway.
I did my MSc in Aarhus, Denmark carrying out research on the serotonin transporter. I then moved to Cambridge to pursue a PhD with Dr Ben Nichols at the MRC- Laboratory of Molecular Biology in the Cell Biology division. Through a Lundbeck foundation Post Doctoral Fellowship I stayed on to maximise the output of my PhD findings. After a six-year stint in Cambridge I via a Post Doctoral Fellowship from the Danish Science Foundation moved to San Diego to work with Professor Kun-Liang Guan. While there I studied the cellular signalling pathway called the Hippo Pathway. In Nov 2015 I was recruited to the University of Edinburgh Centre for Inflammation Research on a Chancellor’s Fellowship to begin my independent career.
I am pleased that our team is diverse, international and that all are great team citizens. While carrying out our Science we strive to be challenged, hard working, inter disciplinary, but also to have fun along the way.
I am a third year PhD student at the Gram Hansen Lab currently studying the interaction between the Hippo pathway and the plasma membrane. Prior to joining the lab, I lived in Berlin, where I did my Undergrad in Biology at The Free University and a Masters degree in Moleculer life sciences at Humboldt University.
Born and raised in Egypt, I moved to the UK to continue my undergraduate studies. I recieved a First Class BSc (Hons) in Cell Biology from the University of Stirling. I later joined the University of Edinbrugh for a MSc by Research in Biomedical Sciences. My PhD project at the Gram Hansen lab is focused on studying the Hippo pathway regulation of Prostate Cancer development, progression and metastasis.
My research focusses on the role of mechanotransduction signals in osteosarcoma in relation to the Hippo pathway. I completed my undergraduate degree in BSc (Hons) Biomedical sciences (Pharmacology) at the University of Edinburgh in 2017. After graduating, I started MRC-funded Doctoral Training Programme in Precision Medicine in the Gram Hansen Lab
(Based at the University of Strathclyde, Prof. Gail McConnell lab)
“In my PhD project I am investigating the Hippo pathway in Malignant Mesothelioma. For that I use advanced imaging techniques in the lab of Prof Gail McConnell at the University of Strathclyde. Before I moved to Scotland, I finished my Master’s degree in Physics at the University of Potsdam.”
- DUNCAN MACLEAN (Honours student), Currently continuing his Medicine Degree at the University of Edinburgh.
- TAMARA HUSSAIN (Honours student), Currently working at Charles River.
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.
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 and gene expression analyses to address these questions.
Prof. Gail McConnell https://www.strath.ac.uk/staff/mcconnellgailprof/
Dr. Pierre Bagnaninchi http://www.crm.ed.ac.uk/people/pierre-bagnaninchi
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
Prof. Donald Salter https://www.ed.ac.uk/pathology/people/staff-students/donald-salter