Monday Lunch Livestream

with Professor Ben Hogan

30 May 2022

Professor Ben Hogan uses model organism genetics in zebrafish to discover new molecular regulators of lymphangiogenesis. This has led to the discovery of new and unexpected mechanisms of human disease and potential new therapeutic targets.

Learn about his discoveries and the unexpected new finding that may offer ways to target diseases of excessive lymphangiogenesis, such as cancer, in the future.

Lymphangiogenesis is the formation of lymphatic vessels from pre-existing lymphatic vessels in a method believed to be like angiogenesis (blood vessel development). Lymphangiogenesis plays an important physiological role in homeostasis, metabolism and immunity.

Lymphatic vessels play key roles in the maintenance of tissue fluid homeostasis, trafficking of immune cells and the metastatic spread of cancer. The formation of lymphatic vessels in both development and disease is driven by the Vascular Endothelial Growth Factor C (VEGFC), which signals through VEGF Receptor 3 (VEGFR3). The targeting of the VEGFC/VEGFR3 pathway is thought to offer much promise in the clinic but has led to mixed results and variable outcomes for patients.

Professor Hogan discusses the recent discovery of a role for the RNA helicase Ddx21 in lymphangiogenesis. Ddx21 is a regulator of ribosomal RNA transcription and ribosome biogenesis and was discovered through genetic screening in zebrafish. His findings show that Ddx21 is regulated in response to VEGFC/VEGFR3 signalling in zebrafish and human cells. This may offer ways to target VEGFC/VEGFR3 signalling outcomes in diseases of excessive lymph-angiogenesis such as cancer metastasis or lymphatic malformation in the future.