Professor Lan devoted his academic efforts to the battle against scarring in the body’s vital organs. He has identified the main pathway that leads to scarring, as well as the molecules that bind with receptors, then proceed down the pathway to the gene and cause or inhibit fibrosis. His discovery could stem the deterioration in patients with diabetes, heart disease or liver damage.
Professor Hui Yao LAN
Department of Medicine & Therapeutics
Hui Yao LAN is a professor of biomedical sciences in CUHK’s Department of Medicine & Therapeutics.
A CUHK research team led by Professor LAN has uncovered a signalling mechanism that leads to tissue scar formation and cancer progression by studying transforming growth factor-beta (TGF-β), a set of proteins that play an essential role in the immune system.
The team found that Smad3, a key molecule downstream of TGF-β signalling, is the ‘bad guy’ and is over-activated in scar tissue and tumour microenvironments. In contrast, Smad7, another protein in TGF-β signalling, plays the ‘good guy’ role, countering the functions of Smad3. When Smad7 is lost, as in scar and tumour tissues, Smad3 overrides, causing scarring.
“I am proud of our new discovery,” said Lan, who has devoted his academic efforts to the battle against tissue scarring and tumour inflammation. “The finding leads to the identification of a new pathway of tissue scarring.”
In the context of the scarring of connective tissues, called fibrosis, Smad3 binds to fibrosis genes and mediates tissue scarring in chronic heart, kidney, liver, and lung diseases. Targeting the molecules regulating gene expression can combat tissue fibrosis.
Importantly, ‘bad guy’ Smad3 can also bind to many check-point genes on immune cells and can cause tissue scarring by converting macrophages to fibroblasts and can promote cancer progression by dysregulating immune system responses to cancer in the tumour microenvironment. Even more recently, Lan’s team discovered that Smad3 plays an essential role in the disease procession of type-2 diabetes and diabetic complications, and deletion of Smad3 corrects the diabetic phenotype in diabetic mice.
These discoveries have led to novel therapies for diseases associated with fibrosis, diabetes, and cancer by rebalancing TGF-β/Smad signalling.
Professor Ng’s research interest is to unveil the causes of inflammatory bowel disease (IBD). Her research group has focused on how environmental factors lead to the disease. And their revelations are now being used to developed targeted therapies for IBD.
Professor Siew NG
Department of Medicine & Therapeutics
Siew NG is Professor at the Department of Medicine and Therapeutics, CUHK and Honorary Consultant at the Prince of Wales Hospital, Hong Kong.
When inflammatory bowel disease (IBD), a lifelong and debilitating gastrointestinal condition, began to increase in Asia two decades ago, the causes were still a mystery. When Siew Ng joined CUHK in 2010 after obtaining her PhD at Imperial College London, she witnessed the explosion of this ‘western’ disease in Asia and began her quest to crack it.
Ng’s team was the first to launch the Asia-Pacific Crohn’s and Colitis Epidemiology Study (ACCESS), which, for the past five years, has tracked several thousands of new cases of Crohn’s disease and ulcerative colitis — the two major forms of IBD — across 15 countries in Asia, as well as Australia. Their studies have revealed that the disease progression of IBD, in both the West and the East, is driven by the interplay of an abnormal immune response and gut microbes. Having identified specific microorganisms that may contribute to the disease, Ng and her collaborators also suggested environmental exposures that can be modulated for disease prevention. These revelations are now being used to develop targeted therapies for IBD.
The ideal time to tease apart the complex web of environmental triggers and genetic associations, says Ng, is before the IBD incidence peaks, when urbanization is happening. “We are going into rural areas of China where IBD is still rare,” says Ng. “We are studying how the environment, diets and gut microbes of rural people differ from those living in China’s megacities.”
Ng’s team is using new approaches, such as genomics and microbiomics, to unlock the aetiology, or set of causes, underlying IBD. “The golden time for identifying the cause of the disease is the next ten years,” says Ng. “We need to seize this golden opportunity now”.