Vicky Nguyen:
Involvement of Tie-2 signalling in lymphangiogenesis
Lymphatic vessels play important roles in immune surveillance, fat absorption, and tumour metastasis. Proper function of lymphatic vessels ensures drainage of excess interstitial fluids and proteins. The lymphatic system complements the blood circulatory system in absorption and transport of nutrients, and in the maintenance of homeostasis. In molecular cell biological research, disproportionately greater amount of attention has been given to the blood circulation, relative to the lymphatic system. The two systems are seldom studied in parallel even though the two systems share various ligands including the angiopoietins and the VEGFs, and certain malfunctions in either system can affect functions of the other.
Angiopoietins 1 and 2 (Ang-1 and -2) have recently emerged as regulators of both angiogenesis and lymphangiogenesis through the Tek/Tie-2 receptor tyrosine kinase. Ang-2, in particular, plays an important role in proper lymphatic function and is implicated in pathological conditions involving deregulated angiogenesis. Development of Ang-2 or its downstream signalling molecules as therapeutic targets for diseases involving lymphatic or blood vasculature dysfunction requires understanding of Ang-2 signalling in both lymphatic and blood endothelial cells.
My strategy to characterize Ang-2 signalling is to use a system of primary bovine endothelial cells: venous, arterial, and lymphatic endothelial cells that I have isolated from mesenteric vessels. The three-cell system will allow comparative study of the lymphatic and blood endothelium within the context of Ang-2/Tie-2 signalling. Understanding the mechanisms of cell-type-specific responses elicited by shared ligands such as Ang-2 will aid the rational design of drugs specifically targeting one system and not the other.
