By Dr Mark Jean-Aan Koh

My name is Dr. Mark Jean-Aan Koh and I head the Department of Dermatology at KK Women’s & Children's Hospital in Singapore.

I will be working with Dr Ene-Choo Tan, a molecular geneticist, on using a third-generation sequencing machine to achieve a higher genetic diagnosis rate for EB patients. This is a new machine that sequences longer stretches of DNA and can reduce the number of EB patients for whom we can’t find a genetic change. You can see Dr Tan (above photo), wearing yellow, standing next to the machine for short-read sequencing and myself next to the third-generation, long-read sequencer here in our laboratory. 

We diagnose and care for both child and adult patients with inherited epidermolysis bullosa (EB). Our goal is to improve the lives and wellbeing of EB patients, not only in Singapore but in the Southeast Asian region.

 

Which aspect of EB are you most interested in?

I am interested in multi-disciplinary care for EB patients, both children and adults. We have set up a multi-disciplinary rare skin conditions clinic in our centre, with specialists from dermatology (skin), ophthalmology (eyes), dentistry (teeth), orthopaedics (bones and muscles), pain, podiatry (feet), physiotherapy, occupational therapy, speech therapy, dietetics (nutrition), and psychology (mental health). I am also passionate about EB diagnosis and management in lesser-served communities, as well as EB pruriginosa, a form of EB that is associated with severe itching. This form of EB is common in the Southeast Asian region.

 

What difference will your work make to people living with EB?

Although there is currently no cure, we can improve the quality of lives of people living with EB. Multi-disciplinary care of EB patients can alleviate and improve the complications associated with EB, especially with early detection and treatment. In lesser-served communities, by providing low-cost, accurate genetic diagnosis to EB patients, we hope to provide better predictions of how a person’s EB will progress over time, more effective treatment, and appropriate genetic counselling. This will reduce the burden of EB on patients, their families, and society. Recently, treatment of EB pruriginosa patients with dupilumab has led to tremendous improvements in managing itching and quality of life.

 

Who/what inspired you to work on EB?

Caring for, working with, and journeying with both children and adults with EB and their families, has inspired me to do more to improve the lives of EB patients.

 

What does the funding from DEBRA mean to you?

With funding from DEBRA, our team will be better able to perform genetic testing for patients with EB, especially for those patients that we were not able to find genetic changes for from regular genetic testing using short-read sequencing. The long-read sequencing platform we will be using is able to detect larger genetic changes such as insertions, deletions and expansions of parts of the DNA sequence, in addition to small sequence changes where  only one or two DNA ‘letters’ are changed or missing.

 

What does a day in your life as an EB researcher look like?

Half my day is spent in the clinics, seeing not only EB patients but also other children with combinations of symptoms that make their diagnosis and treatment complex. It is through my clinical work with all my patients and their families that I understand the unmet needs of people with EB. The other half of my workday is a combination of administrative, research and innovation work. In between, I teach paediatric dermatology and dermatopathology, the study of skin and skin conditions under the microscope.

 

Who’s on your team and what do they do to support your EB research?

Our dermatology team consists of four dermatologists, 10 paediatricians, six dermatology nurses, three dermatology pharmacists, and administrative staff. We work very closely with our hospital’s genetics team and genetics laboratory for the diagnosis of EB patients. We also collaborate with the Skin Research Lab at A*Star, one of the largest research institutes in the world, on some of our EB research.

 

How do you relax when you’re not working on EB?

I try to spend at least one hour a day exercising, either before or after work. I find it relaxes the mind and body, so that I can focus more and think more clearly, and to generate new ideas. I also enjoy music – listening, playing, and composing music, especially church music. I happen to also conduct a church choir. I occasionally indulge in playing Xbox FIFA!

 

What these terms mean:

Molecular genetics = the study of DNA molecules - as opposed to population genetics which looks more at evolutionary changes within groups of plants or animals.

Molecular diagnosis = identifying the specific DNA change causing a person’s EB symptoms.

EB pruriginosa = a form of DEB that is particularly itchy.

Dermatopathology = studying diseases and conditions of the skin under the microscope.

Dietetics = studying how our food and drink affects our health.

Ophthalmology = studying disease and conditions of the eyes.

Orthopaedics = studying muscles and bones.

Podiatry = studying diseases and conditions of the feet and lower legs.

Sequencing = reading the ‘letters’ on the DNA molecule that make up our genes 

Third generation sequencing  = newly developed method for reading longer stretches of DNA, as compared to second generation sequencing which produces lots of short sequences, and the original ‘Sanger’ sequencing which was the main method for around 40 years from its development in the 1970s.

 

This 5min blog from Genomics England explains the difference between short-read and long-read genetic sequencing.

 

Full glossary of scientific terms