February 2015 | ISSUE 16
Facing a global problem: skin researchers look for new treatments

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By Andrea Loh
Higher Executive, Communications & External Relations

With one in three people suffering from a skin disorder, it is no wonder that pharmacy shelves are stacked high with skincare products. But effective treatments for debilitating skin conditions, such as psoriasis, non-healing wounds or eczema, are limited and often lead to unwanted side effects.

To address this need, LKCMedicine has assembled a team of researchers that over the next five years will further our understanding of the mechanisms that maintain skin health and drive disease.

“Our goal is to establish a strong collaborative environment that enables translation of basic discoveries to the clinic and industry, delivering better treatment options for patients with skin conditions,” said Professor of Dermatology & Skin Biology Artur Schmidtchen.

Healing more than wounds

With Singapore's ageing population and rising rate of diabetes, non-healing wounds - which in severe cases can lead to amputations - are becoming increasingly commoln and a cause for concern.

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LKCMedicine Dermatology & Skin Research Team (from top left): Prof Artur Schmidtchen, Prof David Becker, Asst Prof Navin Kumar Verma and Asst Prof Woo Wei Meng

Although treatments are available, most only reduce levels of bacteria in wounds.

To promote healing, Professor of Tissue Repair & Regeneration David Becker has developed a promising antisense oligonucleotide gel-based drug. It not only helps wounds heal twice as fast, but more importantly, it can kick-start the healing process in non-healing wounds.

“At the moment, we are trying to raise funds for a phase III trial of the antisense gel in diabetic ulcers and venous leg ulcers,” said Prof Becker.

At the same time, Prof Becker is collaborating with engineers at NTU to develop a nanoparticle version of the drug to treat ischaemia-reperfusion injuries, such as pressure ulcers. “Using nanoparticles, we can deliver the drug just to the site of the injury to help repair the leaky blood vessels,” said Prof Becker.

If successful, it may also help repair damage to blood vessels in other ischaemia-reperfusion related injuries, such as heart attacks and strokes.


Promoting skin regeneration
Another promising approach focuses on the molecular processes that underlie hair growth. Hair follicles, present all over the body, are easily accessible mini-organs that continuously regenerate.

When the skin is torn, hair follicle stem cells migrate to the wound site, where they regenerate part of the wounded skin. However, as we age, this ability deteriorates.

Assistant Professor Woo Wei Meng hopes to pinpoint the molecules involved in instructing these stem cells to migrate, particularly the signalling interactions with dermal papilla cells, which cluster at the base of hair follicles.

“It could potentially contribute to the development of regenerative medicine that promotes wound healing,” said Asst Prof Woo, who hopes to also shed light on how to regenerate other injured tissues.

‘Tunable’ immune response

Another key factor in skin health is the immune system, which protects us against harmful micro-organisms. But sometimes, regulated immune responses become dysregulated, triggering chronic inflammatory diseases, such as psoriasis, which are significant causes of long-term morbidity worldwide.

Immune reactions in the skin, in particular T-cell adhesion and migration to sites of inflammation, are mainly regulated by the integrin leukocyte function-associated antigen-1 (LFA-1). However, long-term use of LFA-1 targeting drugs causes serious side effects, highlighting the complexity of LFA-1-mediated signalling pathways.

Assistant Professor of Immunology & Cell Biology Navin Kumar Verma and his team are investigating these pathways and their biological significance in T-cells.

“It is important to clearly understand human T-cell functioning at the molecular level, so that targeted and ‘tunable’ therapies which allow T-cell migration to be controlled to treat immune-mediated diseases can be developed,” said Asst Prof Verma.

New drugs and biomarkers

Our innate immunity also plays a key role in maintaining the balance between the body and the one to two kilograms of bacteria it hosts. Understanding these underlying processes in healthy individuals and under different disease conditions may yield novel immune modulation therapies and early disease markers.

“Utilising our body’s endogenous defence mechanisms may give us novel alternatives to currently available antibiotics and antiinflammatory drugs. We may also be able to pre-determine the severity of wounds and skin conditions like eczema,” said Prof Schmidtchen.

The possibility of early diagnostics is not only important for patients, but also the pharmaceutical industry. Understanding these markers may help the industry develop suitable drugs for different types of wounds, skin diseases and inflammatory conditions.

Multidisciplinary and translational research
Going beyond these strategic thrusts, the Dermatology & Skin Biology research team aims to link its research to other areas of strengths of the School, NTU and the new S$100-million Skin Research Institute of Singapore. Particular areas of shared interest span from metabolic and infectious diseases, neuroscience and microbiome research to bioengineering and biomaterials.