Of Butterfly Wings and Fragile Skin – What Science Can Offer

Aug 30, 2015

Ng YiZhen

Research Fellow

Institute of Medical Biology (IMB)

IMB was formed in 2007, with a mission to study mechanisms of human disease in order to discover new and effective therapeutic strategies for improved quality of life. IMB has 22 research teams working in three primary focus areas - stem cells, genetic disease, and skin biology. The teams work closely with clinical collaborators as well as industry partners, to target the challenging interface between basic science and clinical medicine. IMB’s strategic research topics are targeted at translational research to understand the mechanisms of human disease so as to identify new strategies for disease amelioration, cure and eradication and to improve health and wellbeing.

An interview with Harshit, a bright ‘butterfly child’ from Singapore who wants to be in the navy or air-force when he grows up.

©2015 A*STAR Institute of Medical Biology

Blister formed along the epidermis where mutant keratin 14 is expressed in EB simplex skin.

Blister formed along the epidermis where mutant keratin 14 is expressed in EB simplex skin.

©2015 A*STAR Institute of Medical Biology

Prof. Birgit Lane and Dr. Cedric Badowski from the IMB also contributed to the writing of this blog post.

As fragile as butterfly wings, the skin of butterfly children is so sensitive that the slightest touch can cause painful blisters to form. These butterfly children are born with a rare genetic condition known broadly as epidermolysis bullosa (EB). Their skin is unable to withstand the stress of everyday rubs and knocks, and bandages become part of their everyday routine. With technological advances in molecular genetics, as many as 18 causative genes have been identified in skin blistering disorders since the 1990s, leading to great improvements in EB classification and diagnosis. However, there is currently no effective therapy and cure for EB.

Blisters seen on the foot of an EB butterfly baby.

Blisters seen on the foot of an EB butterfly baby.

© 2015 National Skin Centre, Singapore

EB affects more than 30 families in Singapore, and an estimated half a million worldwide. Research into EB has provided deep insights into general skin biology, wound healing, and basement membrane structure and function. Your skin is made up of multiple layers of tightly packed cells (epidermis) which seats on top of a collagenous cushion (dermis). To anchor the epidermis down to the dermis in healthy skin, there exists a highly organized network of specialized interconnected structures. These structures consist of intermediate filaments like keratin, hemidesmosomes, anchoring filaments and anchoring fibrils. In the case of EB, mutations in the genes of these specialized structures lead to loss of adhesion within the skin, and blistering results.

The keratin network in each keratinocyte is stained fluorescent green: (Left) Normal filamentous keratin network seen in healthy keratinocyte. (Right) Abnormal keratin network with aggregates (small bright spots) seen in mutant EB keratinocyte.

The keratin network in each keratinocyte is stained fluorescent green: (Left) Normal filamentous keratin network seen in healthy keratinocyte. (Right) Abnormal keratin network with aggregates (small bright spots) seen in mutant EB keratinocyte.

©2015 A*STAR Institute of Medical Biology

With funding from an EB charity (DebRA International), we are working on understanding the mechanisms behind EB blistering and an effective therapy for EB. Mutations in the keratin gene can lead to dysfunctional keratin filament networks which clump together to form keratin aggregates in skin cells of patients with EB (simplex subtype). Our research suggests that the keratin aggregates in these EB skin cells may be reduced by the application of certain drugs. We hope to eventually develop promising treatments such as a cream formulation which could increase the strength of the EB skin, and give the patients a better quality of life.

Dr Yi Zhen Ng is a research fellow in the Epithelial Biology Laboratory at the Institute of Medical Biology. She was awarded the A*STAR-University of Dundee PhD scholarship where she studied skin tumor microenvironments. Her interests lie in exploring the importance and diversity of this tissue microenvironment, and she is currently modeling skin cancer and skin blistering disease for use in drug screening.

Dr. Cedric Badowski is a senior research fellow in Epithelial Biology Laboratory where he studies the complex molecular mechanisms underlying the skin fragility of patients suffering from Epidermolysis Bullosa Simplex Dowling-Meara (EBS-DM), a severe form of skin blistering disorder. Since 2012, his research has been funded by 2 international grants from DebRA (Dystrophic Epidermolysis Bullosa Simplex Research Association) to identify potential drug candidates which could reduce the painful blisters associated with this disease.

Prof E. Birgitte Lane is the executive director of A*STAR’s Institute of Medical Biology and principal investigator of Epithelial Biology Laboratory. She is also co-director of the Skin Research Institute of Singapore, with Prof Roy Chan. Her research career has focused on epithelial biology, particularly in genetic skin diseases, the keratin filament cytoskeleton, skin cancer and recently wound healing.