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The project combines our long-standing interest in determining how Wnt signalling contributes to lung development and repair with bioengineering approaches to target protein delivery to the lungs.

We will determine whether administering Wnt5a (a potential pro-repair protein) to the lungs can strengthen the capacity that the lungs already have to repair themselves. This protein has been shown to stimulate lung stem cells after injury occurs and it is these stem cells that are needed to drive the lung repair process. However we don’t yet understand exactly how the Wnt5a protein carries out this key role and this is what we will determine. We will use time-lapse imaging to video the response of lung cells to Wnt5a treatment and track exactly how this protein stimulates repair. As part of this proposal we will also encase Wnt5a protein in tiny particles of gel and formulate a Wnt5a-gel treatment that can be administered to the lungs to stimulate repair. Encasing Wnt5a in a degradable gel will enable sustained and targeted administration of this treatment.

Dr Sally Kim has been integral to the development of this project which she will co-lead through her role as a researcher co-investigator.

After being postponed for 2 years, NHLI Research Away Day was back again!

The Away Day was held on a beautiful day on Friday 17 June 2022 at the Queen Elizabeth II Conference Centre. It was a great opportunity for all staff and students to meet colleagues and to learn the breadth of research across NHLI!

Dr Sek-Shir Cheong gave a talk on ‘Temporal Control of DNA recombination and mRNA delivery in ex vivo Precision-Cut Lung Slices’, describing novel methods that our lab recently established to manipulate genes/targets in adult tissue-based models.

Our recent article ‘The Planar Polarity Component VANGL2 Is a Key Regulator of Mechanosignaling’ published in Frontiers in Cell and Developmental Biology has been selected to be featured in the collection “Editor’s Pick 2021: Highlights in Cell Adhesion and Migration”.

https://www.frontiersin.org/research-topics/30228/editors-pick-2021-highlights-in-cell-adhesion-and-migration#articles

This article highlights a previously unknown function of the core planar cell polarity (PCP) protein, VANGL2, in control of mechanosignalling and we propose this underlies the key role of the PCP pathway in tissue morphogenesis and repair.

We employed a combination of live imaging of ex vivo 3D precision-cut lung slices, in vitro 2D cell culture and functional assays to show that disrupted epithelial cell migration in Vangl2^Lp (Looptail) mutant mice was caused by underlying aberrant cell mechanics. Our findings were further consolidated by the use of sophisticated elastic micropillar arrays that demonstrated abnormal cellular traction force in epithelial cells from Looptail mutant mice (collaboration with Dr Armando del Río Hernández, ICL Department of Bioengineering).

Click the link below for more details about this study:

VANGL2 (Van Gogh-like 2): In Control of Mechanosignalling

The full article can be found here :

https://www.frontiersin.org/articles/10.3389/fcell.2020.577201/full

After 4 years in the lab, Róisín is off to begin a new role training to be a Clinical Trials manager at Medpace. Róisín came to the lab as a Master’s student and was subsequently awarded a PhD to study the role of retinoic acid in lung repair. After completing her PhD in early 2021, Róisín stayed on for a year as a post-doc. During her time in the lab Róisín worked to establish a novel model of lung injury and repair (Kim-Mongey et al. 2021 Biomaterials) which she then used to investigate the role of retinoic acid. In addition, Róisín has shown an important role for dietary vitamin A intake on lung function through large-scale population studies (collaboration with Dr Cosetta Minelli).

We wish Róisín every success in her new role!

“I was made to feel a part of the team as I attended weekly laboratory meetings with the group, which enabled me to keep up with and gain an understanding of the current research” – Onyinyechi

“As part of my master’s degree in Cardiovascular and Respiratory Healthcare at Imperial College London, I spent four months with the Dean group. Here I undertook a research project that investigated lung development in mouse models of Down syndrome. I was supervised by Charlotte Dean and Sek Shir Cheong who taught me how to analyse sections of lung histology using the software Fiji, as well as how to use a range of scientific databases for genetic analysis.

The research we carried out was important in adding to the small number of studies that had previously investigated lung development in Down syndrome. In our study, we used a range of mouse models which all had three copies of different portions of chromosome 21. This allowed us to narrow down and identify the region of chromosome 21 that was critical in the development of the abnormalities found in the lung histology of these mouse models and the possible candidate genes causing them.

I was made to feel a part of the team as I attended weekly laboratory meetings with the group, which enabled me to keep up with and gain an understanding of the current research taking place at the lab. Additionally, observing presentations, as well as delivering some myself to the group, helped me to develop my presentation skills and allowed me to progress quicker as I received useful and regular feedback. I had a great time working at the lab, especially as I had not done any work like that before.”

– Onyinyechi

“My time in the Dean lab allowed me to develop a deeper understanding into how ideas are developed in the lab and how much collaboration is involved in research.” – Lauren

“For my master’s thesis I was lucky enough to undertake a 6-month research project with the dean lab. This experience was incredible, for the first time I was truly integrated into a labs’ research. For my project I was able to work with the on the Acid Injury Repair (AIR) model. This novel model uses hydrochloric acid to mimic lung injury and allows for the study of lung repair and regeneration. Working with Rosin Mongey, who established the AIR Model, I tested ways to image dynamic processes happening in the injured tissue.

Throughout my project I learnt new techniques and concepts. Thanks to the great supervision of Rosin and the FILM department, I became confident with microscopy, an area I knew little about. As microscopy is a central technique in biological research, these newly developed skills will help me in future research.

Alongside my lab work, I was invited to attend weekly lab and section meetings. These meetings helped to highlight the collaborative nature of research. In lab meetings I was kept up to date with the labs work and was able to present and receive feedback on my own, whilst in section meetings, I learnt about the research being performed by other groups.

My time in the Dean lab allowed me to develop a deeper understanding into how ideas are developed in the lab and how much collaboration is involved in research. I hope that the skills I have learnt during this project will help me in a future research career.”

– Lauren

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Walking through my local shopping centre the other week, I was surprised to see this new store that has just opened (see picture). It’s clear that ‘Regenerative Medicine’ is something the public responds favourably to. As a lab that conducts research aimed at identifying novel regenerative medicine treatments for lung disease, our hope is that funding agencies will be equally responsive to supporting research in this important area.

The ERS has published a new monograph focused on lung stem cells.

A variety of experts in the field discuss how stem cells can be generated or stimulated from endogenous lung tissue. The book also contains several chapters on modelling lung and stem cell functions including a chapter on our own favourite model- precision-cut lung slices.

https://www.ersbookshop.com/lung-stem-cells-in-development-health-and-disease-669-p.asp

31^st March 2021 – Massive congratulations to Róisín on a very successful PhD!

Róisín defended her thesis entitled ‘Investigating the role of vitamin A and retinoic acid signalling in lung homeostasis and repair’ and passed her viva without corrections! This coincided with the UK lockdown restriction easing and we were able to share a toast in a socially distanced manner on the beautiful Queen’s lawn.