The objective of the Weng lab is to investigate and manipulate the innate immune systems using chemical biology, and to develop lead compounds and protein drugs against inflammatory disorders. The immune systems defend us against external infection and internal damage. Dysregulated equilibrium between activation and tolerance of immune responses is the key causal element to numerous disorders, including cancers, autoimmune diseases, and ageing. Innate immune disorders can be treated with small molecules (e.g. NSAIDs) and protein drugs (e.g. TNF blocker). Yet, many inflammatory diseases are still hard to treat. We see major opportunity to modulate immune equilibrium and restore homeostasis by targeting the innate immune inhibitory pathways, starting with the anti-inflammatory hepatokine GDF15.
Colchicine is a common anti-inflammatory medicine that is finding new uses
Colchicine is one of the popular medicines with around three million prescriptions per year in the US. It treats acute inflammation and provides life-long protection in the autoinflammatory disease FMF. Interest of colchicine has grown steadily in the last decade thanks to repurposing trials in cardiology, dermatology and other diseases where myeloid cells drive inflammation. How does colchicine treat inflammation? Colchicine concentrates in the liver. We proved that it acts selectively in the liver hepatocytes.
Novel inter-organ communication from liver to myeloid cells blocks inflammation
We have discovered a novel axis of liver-myeloid cell communication and identified the colchicine-triggered, anti-inflammatory hepatokine GDF15. We characterized the molecular pathways by which GDF15 is induced in liver, and by which it inhibits activation of myeloid cells.