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.

“The conference was a great opportunity to interact with experts in the field and to learn about exciting new developments at the cutting edge of lung regenerative science.” – Róisín

“In March 2021 I won a bursary to attend the 19^th European Respiratory Society Lung Science conference and present my work on ‘Investigating the role of vitamin A intake and retinoic acid signalling in lung homeostasis and repair- a multidisciplinary approach’. The presentation summarised key findings from my PhD: using dietary intake and genetic data from the large UK Biobank population to study the association between vitamin A intake, retinoic acid pathway genes and adult lung function in addition to lab-based work using our novel Acid Injury and Repair (AIR) model to study and manipulate RA signalling following lung injury. The presentations involved an online poster as well as 3 minute oral presentation followed by a stimulating discussion session. I thoroughly enjoyed the experience and was honoured to win the best poster award for my session.

As a recipient of a bursary award, I was also able to take part in the mentorship programme during which I received invaluable advice on my career progression from leaders in the field.

The organisers did an exceptional job putting together the conference programme despite the challenges of an online format. There were many exciting talks from leaders across the field of lung repair and regeneration. Topics covered cellular differentiation and interaction in the alveolar niche, exciting novel scaffolds to replicate and repair the lung and new in vitro and ex vivo models for the study of lung disease and repair to name a few. The conference was a great opportunity to interact with experts in the field and to learn about exciting new developments at the cutting edge of lung regenerative science.”

– Róisín

 

Studying the mechanisms of lung repair and regeneration in the human lungs is challenging given their critical role. We have developed a new model, using slices of lung tissue, that can be used to study lung repair and regeneration. The Acid Injury and Repair (AIR) model works by using hydrochloric acid to injure a small part of the tissue slice whilst the surrounding area remains uninjured. This mimics the pattern of injury often observed in lung diseases. The AIR model enables tracking of different cell types, including stem cells as well as providing a platform to test potential new treatments to repair the lungs.

Researchers Sally Kim and Roisin Mongey worked on developing and validating this new tool which was recently published in Biomaterials. You can read about their work on the Imperial Faculty of medicine blog http://wwwf.imperial.ac.uk/blog/imperial-medicine/2021/01/13/a-breath-of-fresh-air-in-the-study-of-lung-repair-and-regeneration/

Our new research article “The Planar Polarity Component VANGL2 Is a Key Regulator of Mechanosignaling” has been published in Frontiers in Cell and Developmental Biology. 

In this study, Dr Sek Shir Cheong discovers how a mutation in the VANGL2 gene (Vangl2^Lp), in mutant mice, interferes with normal mechanosignalling and directed cell migration which contribute to abnormal formation of alveoli, the site of gas exchange in the lungs. Mechanosignalling, “mechano-signalling”, simply put, is a signalling process induced by mechanical forces.

By monitoring in real time the movement of alveolar epithelial cells (an important cell type that form alveoli) in slices of lung tissue, we found that cells from the Vangl2^Lp/+ mutant mice had slower and more restricted movement compared to cells from normal healthy mice. This resulted in fewer alveoli being formed, which reduces lung function in the mutant mice. To help us understand what causes the abnormal movement in these mutant cells, we isolated epithelial cells from the tracheas and lungs of Vangl2^Lp/+ mutant mice, and labelled different components in the cells using antibodies. This process revealed that the Vangl2^Lp mutation caused disruption of the actomyosin network (a kind of scaffold present in  cells that is analogous to the musculoskeletal system in the human body), as well as focal adhesions, which function as molecular clutches, enabling cells to attach to their surrounding matrix. In addition we found a reduction in key proteins responsible for mechanosignalling within the lung epithelial cells. All of these abnormalities leads to the the cells being floppy as they are unable to generate force, thereby affecting their ability to move or migrate which is particularly important during the process of lung formation or lung repair after injury. 

Lastly, we tested a drug WNT5A, a molecule that belongs to the same pathway as VANGL2, and showed that it could improve wound healing ability in the mutant cells, suggesting that WNT5A could be a potential target for lung repair. 

This article highlights a previously unknown role of VANGL2 in command and control of mechanosignalling.

 

During my second year of medical school I decided that I wanted to gain some lab experience over Summer, as I realised medical research was an area I’d like to explore further. I was very fortunate to arrange to spend my Summer in the Dean lab and subsequently worked with Charlotte and Matt to design a project that would contribute to the labs work in investigating the mechanisms underlying Congenital Pulmonary Airway Malformation (CPAM). I applied for and gratefully received a Wellcome Student Scholarship to facilitate this, producing a report based on my findings. I found it a fantastic experience working within the research team and gained valuable insight into clinical academia through collaborating with clinicians at the Royal Brompton Hospital.

I have subsequently presented the results of my project at the 2019 Pathology Society Winter meeting held at the Royal Society of Medicine, and this year our article was published in BMJ Thorax. DOI: 10.1136/thoraxjnl-2020-214752.

My experience in the Dean lab has been integral to informing my choice to pursue academic research alongside my clinical work. I have since completed my BSc at Imperial in Cardiovascular Sciences, during which I conducted a lab project at Tokyo Medical and Dental University, and I am currently working as an academic foundation doctor in which I will complete my academic rotation in transplant and regeneration at Addenbrooke’s hospital, Cambridge.

Taylor B et al. Mechanism of lung development in the aetiology of adult congenital pulmonary airway malformations. Thorax 2020

A new study cross-disciplinary study from several groups in NHLI demonstrates the importance of lung development genes in regulating adult lung function. This project used UK Biobank to investigate whether lung development genes influence adult lung function. Future experimental investigation of these developmental pathways could lead to druggable targets to improve lung function.

Am J Respir Crit Care Med. 2020 May 11. doi: 10.1164/rccm.201912-2338OC. Online ahead of print.PMID: 32392078

A new paper from Sally Kim and colleagues looks at the potential for stem cells and Extracellular vesicles as potential treatments for lung damage caused by COVID-19.