Cancer Research UK

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London Research Institute

Taija Makinen : Lymphatic Development

Goals

Lymphatic vasculature constitutes a network of vessels critical for fluid homeostasis and immune surveillance. Dysfunction of lymphatic vessels leads to lymphoedema, while in cancer the metastatic tumour cells can spread via lymphatic vessels to the lymph nodes, necessitating radical surgery that destroys the vessel network and frequently causes secondary lymphoedema. Our laboratory aims to understand, at the molecular level but in the context of a living organism, the regulation of lymphangiogenesis and to use this knowledge to gain insights into the mechanisms underlying lymphatic disorders. We use molecular, cellular and genetic approaches, combined with real-time in vivo multiphoton imaging, to elucidate the mechanisms by which a functional lymphatic vasculature is generated. It is hoped that these studies will lead to novel therapeutic approaches to stimulate lymphatic vessel growth and repair in lymphoedema, and to inhibit lymphangiogenesis and associated metastasis in cancer.

Selected Papers

Bazigou E, Lyons OTA, Smith A, Venn GE, Cope C, Brown NA and Makinen T. Genes regulating lymphangiogenesis control venous valve formation and maintenance in mice. J Clin Invest. 2011;121(8):2984-92. doi: 10.1172/JCI58050 (Abstract)
Bazigou E, Xie S, Chen C, Weston A, Miura N, Sorokin L, Adams R, Muro AF, Sheppard D, Makinen T. Integrin-a9 is required for fibronectin matrix assembly during lymphatic valve morphogenesis. Dev. Cell. 2009;17:175-186 (Abstract)
Haiko P, Makinen T, Keskitalo S, Taipale J, Karkkainen MJ, Baldwin ME, Stacker SA, Achen MG, Alitalo K. Deletion of vascular endothelial growth factor C (VEGF-C) and VEGF-D is not equivalent to VEGF receptor 3 deletion in mouse embryos. Mol. Cell Biol. 2008;15:4843-4850 (Abstract)
Mäkinen T, Adams RH, Bailey J, Lu Q, Ziemiecki A, Alitalo K, Klein R, Wilkinson GA. PDZ interaction site in ephrinB2 is required for the remodelling of lymphatic vasculature. Genes Dev. 2005;19:397-410 (Abstract)