Professor Sejal Saglani: Getting to know Rosetrees researchers

Professor Sejal Saglani: Getting to know Rosetrees researchers

Rosetrees researcher profile: Professor Sejal Saglani, Imperial College London

Who Rosetrees Trust is funding
Professor Sejal Saglani leads the childhood severe asthma research programme at the National Heart & Lung Institute, Imperial College London. Her research focuses on investigating how childhood asthma starts, and finding new treatments to treat, but also to prevent asthma.

Professor Sejal Saglani

Asthma is predominantly a childhood onset disease and affects over 1 million children in the UK. It results in symptoms of difficulty in breathing, breathlessness and wheezing and acute attacks which frequently require hospitalisation. In studies that have followed children from birth, approximately one-third of all preschool children under 5 years have suffered from wheezing attacks, usually caused by common cold viruses, and one-third of those preschool wheezers progress to develop asthma in later life. The children that develop asthma suffer a reduction in lung function, and this loss never recovers even into adulthood. Children with asthma, especially those with severe asthma, therefore go on to develop a lifelong illness.

It is known that certain environmental exposures are protective from the development of asthma, this includes being raised on a farm with traditional cattle farming practices. Professor Saglani is investigating which components of the “farmyard environment” are protective.

Professor Sejal Saglani’s lab is aiming to find new treatments that can stop progression of wheezing in preschool children to asthma and also to stop the permanent loss in lung function to adult life.

“We want to know what it is about the cattle farm environment that stops children from getting asthma, so that we can make it into a preventive asthma treatment for use in the UK.”

How Rosetrees Trust have supported Professor Sejal Saglani
Professor Sejal Saglani is a Rosetrees Trust-funded researcher at Imperial College London who has received funding from Rosetrees for 1 project, starting in 2018.

What the outcomes are of Rosetrees Trust-funded research from Professor Sejal Saglani
Professor Sejal Saglani has previously shown that specific bacteria that are inhaled from the farmyard environment are protective in a mouse model of “asthma” (Science Immunology, 2018). She is now investigating how this protection occurs, and also whether it occurs in children with virus infections and wheezing. The aim is to find the component of the farmyard bacteria that confers protection and formulate this into a compound that may achieve prevention of childhood asthma.

Written by: Dr. Rebecca Downing and Professor Sejal Saglani

Joubert syndrome: rare disease, genetics, gene modifiers, and therapies

Joubert syndrome: rare disease, genetics, gene modifiers, and therapies

Professor John Sayer and his team have recently completed a Rosetrees Trust-funded project which aimed to further develop their nephronophthisis (NPHP) mouse model, and subsequent treatment opportunities, at Newcastle University. NPHP is an early onset cystic kidney disease, and it is the lethal component of an incurable, inherited disorder known as Joubert syndrome. Currently, treatment options for NPHP are limited to symptomatic therapy. Therefore, Professor Sayer’s research will help bring treatments for NPHP to the clinic.

Professor John Sayer

In their latest paper, published in the Proceedings of the National Academy of Sciences (PNAS), Rosetrees Trust funding has helped support their research on the identification of a “modifier gene” involved in cystic kidney disease. Using their mouse model, they showed for the first time that the single locus, Barttin, is a modifier. Then, in a cohort of patients, they also showed that the human homolog plays a similar role in disease. These findings provide researchers with a novel potential target to exploit in their model systems, which could have future use in patients. Through altering levels of modifier genes, this may alleviate the effects of Joubert syndrome.

Sayer Lab

Professor Sayer said: “We have elegantly shown using mouse and human DNA samples that Barttin modifies the severity of kidney disease in Joubert syndrome. This is the first time that a modifier gene for cystic kidney disease has been identified. This information will improve diagnoses and will be used to develop therapies to reduce the severity of kidney disease in affected patients.”

“Our research is a major step forwards proving the power of using mouse models to study rare human inherited disease and in the future we may be able to offer a therapy that switches on the protective modifier gene and reduces the development of genetic kidney disease.

“This work paves the way towards personalised therapies in patients with the inherited kidney disease.”

Overall, this research offers new hope to understanding the genetic, and mechanistic, basis of rare diseases to ultimately improve diagnoses and treatment options.

Written by: Dr. Rebecca Downing and Professor John Sayer