Our Research centres on tissue homeostasis with a particular focus on the Hippo pathway and its role in driving tumour and regenerative niches. We have a special interest in how cells sense stimuli at the plasmamembrane and how these cellular responses are transduced to cellular function and memory. We have shown a direct link between both caveolae and clathrin mediated endocytosis and the Hippo pathway, and how distinct mechanical stimuli, such as shear stress and hydrostatic pressure is sensed via these plasmamembrane domains. We strive to provide fundamental insights into the Hippo pathway, and how plasmamembrane domains are integrated into different cellular processes and across cell types. We use interdisciplinary and collaborative approaches, including collaborations with physicists and clinicians. To gain new insights, we take advantage of a range of cellular and in vivo model systems, as well as new imaging modalities and ‘omics’ approaches. Currently, we have ongoing projects on the Hippo pathway’s role in the immune system, biophysical profiling, mechanotransduction, including response to Hydrostatic Pressure and resistance to therapeutics. In addition, we are identifying small molecule modulators of the Hippo pathway and seek to understand how the Hippo pathway drives developmental processes. We have ongoing projects on stratification of Pleural Mesothelioma, as well on Prostate Cancer.

Overall, we believe that understanding fundamental regulation at the molecular level is necessary to fully explore the therapeutic possibilities of targeting this pathway.

We are based at the newly opened Institute for Regeneration and Repair, Edinburgh University at the BioQuarter campus

Panel 1

The TEAM

Meet the people behind the science.

Dr Carsten Gram Hansen

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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, via a Post Doctoral Fellowship from the Danish Science Foundation I 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 set up a new lab. I am now a Senior Lecturer.

Current memberships: Biochemical Society and ASCB

I am pleased that our team is diverse, international and that all are great team citizens. Through our shared interest in discovery based inter disciplinary Science, we seek to address fundamental biological questions. We strive to be challenged and to make important discoveries, but also seek to have fun along the way.

 

Susanna Riley – PhD student (2019 -)

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Originally from rural West England, I completed a BA (Hons) in Cell and Systems Biology at the University of Oxford in 2017 before moving to the University of Edinburgh for an MSc by Research in Biomedical Sciences. I then began the Wellcome Trust PhD programme in Tissue Repair. My research in the Gram Hansen lab focusses on the role of the Hippo pathway in embryonic development and regeneration using the zebrafish.

Read about Susanna’s work

Dr Richard Cunningham – Post Doc (2019 -)

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After completing my undergraduate studies at Trinity College Dublin, I came to Scotland where I obtained my MSc in Bioinformatics at the University of Glasgow. I stayed on in Glasgow, subsequently carrying out my PhD in Professor Andrew Biankin’s group, exploring the potential in targeting tumour metabolism in pancreatic cancer. As part of the Gram Hansen lab, my research is centred on disentangling the role of the Hippo pathway in the formation and progression of malignant pleural mesothelioma.

Read about Ricky’s work

https://doi.org/10.1038/s43018-021-00259-9

DOI: 10.1126/sciimmunol.abj2132

doi.org/10.1042/CS20201474

Krishna Purohit – PhD student  (Sep 2020 – )

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I have a BSc honours in Biochemistry and hold masters in Biochemistry (University of Edinburgh) and Bioinformatics and System Biology (University of Manchester). As part of the MRC Precision Medicine DTP my PhD project in the Gram Hansen lab focuses on investigating the role of cancer mutations using a novel omics technique called proteogenomics, with the aim of stratifying diagnosis and treatments for mesothelioma patients.

Read about Krishna’s work here and

https://doi.org/10.1038/s43018-021-00259-9

Siyang Jia – PhD student 2021 –

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Sijang was a MSc student with us and is now back for more! Siyang is part funded by the CSC and is studying how the Hippo pathway regulates cancer onset and development. 

Read about Siyang’s work

Here, Here and Here

 

Nancy Hui PhD Student July 2022 –

Nancy is part of the Martin Lee PhD program and is studying how the Hippo pathway modulates ageing.

Read about Nancy’s work here

Michaela Noskova PhD Student Sep 2022 –

Michaela is a Prec Medicine PhD student and developing xenograft model systems. Here sitting on top of Calton Hill

Work from Michaela (from previous lab, but nonetheless beautiful!)

Lisa Kölln – PhD student (2017-)

foto Lisa website copy.jpg

(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.

Read about Lisa’s work

and more and more ….

——————-Alumni—————–

Dr Omar M. Salem – MSc (2018), PhD student (2018-2021), and Post Doc 2022

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“Born and raised in Egypt, I moved to the UK to continue my undergraduate studies. I received a First Class BSc (Hons) in Cell Biology from the University of Stirling. I later joined the University of Edinburgh for a MSc by Research in Biomedical Sciences. My PhD project (2018-2021) at the Gram Hansen lab was focused on studying the Hippo pathway regulation of Prostate Cancer development, progression and metastasis. He also worked on the Hippo pathway as a therapeutic target.”

Read about Omar’s work, here and here

Dr Salem went onto work as a Researcher at Artios, Cambridge UK

Dr Jiwon Park – PhD student (2017 – 2021)

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“My research focused on the role of mechanotransduction signals 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 on the  MRC-funded Precision Medicine Doctoral Training Programme in the Gram Hansen Lab. “

Read about Jiwon’s work doi: 10.1016/j.cub.2018.11.066

doi.org/10.1042/BST20200253

https://doi.org/10.15252/embj.2021108719

Dr Park then moved onto becoming a Patent attorney at Marks & Clerk.

Dr Valentina Rausch – PhD Student (2016 – 2019)

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Alumni of the Gram Hansen Lab, revealed the interaction between the Hippo pathway and caveolae. Dr Rausch was the first PhD student in the lab, and handed her thesis in after 3 years and 18 days! Then moved onto an academic Post Doc.

Read about Valentina’s work while in Edinburgh

DOI: 10.1016/j.cub.2018.11.066,

DOI: 10.1007/978-1-4939-8910-2_8.

DOI: 10.1128/mBio.02857-19.

DOI:https://doi.org/10.1016/j.tcb.2019.10.005.

 
MSc and Honours
  • 2022 Shijia Lin MScR 2nd project Biomedical Sciences. Obtained overall a distinction. Now in Singapore for her PhD.
  • 2022 Yue Lin MScR 2nd project, Biomedical Sciences. Also stayed on with us as an intern for three months. Currently applying for PhD positions. Read about Yue’s work here
  • 2020 Jon Corres (MScR) 2nd Project. Obtained overall a Distinction. Then moved on for a PhD student back in Spain.
  • 2020 Josh Martin (MScR) 2nd Project. Obtained overall a Distinction. Then moved on for a PhD student at BARTS Cancer Center.
  • 2019-2020 Emelie Shepherd (MScR) 1st Project. Obtained overall a Distinction.
  • 2018 Duncan Maclean (Honours student), then moved on to continuing his Medicine Degree at the University of Edinburgh.
  • 2017 Tamara Hussain (Honours student), moved onto working at Charles River.

SUMMER INTERN

Michael Marcin, Summer Intern 2022. Awarded a Biochemical Society Stipend. Comming back to us in Sep 2023 for a PhD studentship!

Panel 2

Research

Overview

The body is constantly making new cells. If they are healthy and regulated properly, these cells replace old dead cells so the body can grow and repair organs that have been damaged. However, if this is uncontrolled too many cells could be made, leading to tumour formation.

In recent years a group of related proteins known as the ‘Hippo Pathway’ has been identified as a regulator of this cell proliferation. Hippo pathway proteins such as YAP and TAZ respond to diverse changes in the cell’s environment with alterations in the rate of cell proliferation, activation of the immune system, and generation of new cell types, amongst others.

An infographic showing cells with low YAP/TAZ activity undergoing normal cell proliferation to replace unhealthy cells, and cells with high YAP/TAZ activity undergoing uncontrolled cell proliferation to form tumours.

How these proteins are regulated and how they perform their functions is the subject of our research, with our focus ranging from molecular to whole body processes. This includes the study of cancer, regeneration, and inflammation using imaging of cells grown in the lab and zebrafish, genetic editing, biochemistry, and gene expression analyses. This all helps towards our eventual aim of identifying targets for more effective cancer treatments with fewer side effects.

scientific Background

Cellular proliferation and differentiation must be tightly regulated to maintain tissue mass and homeostasis. If this regulation is lost cellular overgrowth and cancer occurs. However, proliferation and differentiation need to be under dynamic control for developmental and regenerative process. 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 shuttle to the nucleus. There, they predominantly bind to, and regulate the activity of, the TEAD family of transcription factors. These transcription factors promote the expression of a range of genes, including those involved in stem cell proliferation and differentiation, immune system activation, and the extracellular matrix.

An infographic showing cells with high YAP/TAZ activity have roles in immune system activation and infiltration, extracellular niche development and regulation, dedifferentiation and stem cell activation and regenerationt, and tumour formation, leading to cancer metastasis and drug resistance. Medicines are shown to inhibit tumour formation.

Recently, the understanding of the regulatory mechanisms of the Hippo pathway has become a major focus, especially in cancer biology and regenerative medicine. A wealth of cellular regulators has been identified, but how the dynamic subcellular regulation of the core players occurs is not well understood and we seek to answer this fundamental process. We also seek to understand the role of the Hippo pathway in biological processes important for human health with a focus on regeneration, inflammation and cancer.

We are a collaborative and interdisciplinary lab, that utilises live 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.

Internal webpage

Collaborators

Prof. Janne Lehtiø https://ki.se/en/onkpat/janne-lehtios-group

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

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

Prof Chris Ponting https://www.ed.ac.uk/profile/chris-ponting

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

Prof. Neil Carragher  https://www.ed.ac.uk/cancer-centre/research/carragher-group

†Dr. Andrew Sims 

 

Panel 3

Major Funding

wcr - logo aPresent major funder


Additional and previous Funding

Completed Funding
Completed Funding
Completed Funding
Panel 4

Join Us

PostDOCs: We are Always looking for motivated scientists with a strong track record to join us.
We will support excellent candidates to pursue personal fellowships. these are an excellent way to facilitate your  INDEPENDENT CAREER.

Individual Postdoc Fellowships opportunities: BBSRC Discovery Fellowships (March-May), Marie Curie Individual Fellowships (Apr-Sep), Newton International Fellowships, MSCA call July -Sep.  EACR Astra Zeneca, Wellcome, EMBO Fellowships,  Newton International INDIA Fellowship,  FEBS Long Term Fellowships ( September – ?), CSO.

Happy to discuss current projects, possible projects that you might be interested, are your entire own ideas and share our (hopefully) soon to be published papers. We have three research publications under review, so it is a  good time to join us! Feel free to reach out to team members to discuss how the lab works! Also please see additional information here from UoE etc…. For the right candidate, we are excited to help develop your career.

Please allow for time to discuss and develop your project before the deadline. 

These types of personal fellowships are excellent ways to transition towards independence, and we would be excited to facilitate and develop your research to obtain this goal with you.

Currently we have no funded positions available.

PhD STUDIES

We will likely have an opening for a cancer project, that will open around May 2023, with an expected start date in September 2023.  Please reach out by email, if interested, and include your CV and state why you want to join us, and we will let you know when this position might open.

We usually have projects available. 

However, we advertise annually competitive awarded PhD positions. If you are motivated and and think you are competitive for PhD programs, please reach out, so we can discuss how to proceed. Internally funded PhD studentships are available for students. The application to these scholarships generally opens between Oct – Dec (sometimes also in the Spring). 

In addition, institutional shortlisting for the Carnegie Trust to take place in late Jan. Here you need to be en route for (or already have obtained) a first Class Honours from a Scottish university. Please see the Carnegie Trust for further information, as well as this competitive opening.

There are international funding such as Boehringer Ingelheim, with multiple deadlines during the year. Your country of origin, or where you reside might also have PhD Fellowship.

Projects centres likely around the Hippo pathway, caveolae, mechano transductions cancer, cell size regulation, macrophages, development and regeneration and/or zebrafish. We aim for that all PhD students, upon completion of their studies, should come out with a first authored publication. Do feel free to contact me in advance if you would like to undertake your PhD research with us. We  are also interested in supporting self-funded PhD students if your interest align with ours and we think we would be a good fit.

Please also feel free to reach out to current members to find out how it is to work in the lab. Team members email addresses can be found under “The Team“.

We are a supportive lab that want YOU to succeed!

Email Dr. Carsten for inquiries

DIVERSITY & INCLUSION

We are committed to maintaining a safe and inclusive environment for everyone, regardless of race, age, gender, gender identity, sexual orientation, religion, nationality, socio-economic status, or disability. We will continuously strive to attain equity in research by promoting a respectful lab environment and being transparent in our work.

We believe that open, honest communication, professionalism in science, and a diverse workforce allows us to create new ideas and excel academically.