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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.

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