研究概要

Endothelial cells line the inner surface of blood vessels and are subjected to the mechanical forces of blood flow and pressure. While these haemodynamic forces can instruct cellular processes such as lumen expansion, they need to be tightly controlled for the formation of healthy, well-patterned blood vessels. Previous studies from my lab demonstrated that endothelial cells generate a balanced network of branched and linear actin bundles at the cell cortex to resist the deforming forces of blood pressure. When compromised, membrane blebbing, cell enlargement and vessel dilation occur. These findings highlight a critical function of endothelial mechanoresponse to haemodynamic forces to regulate vessel architecture and that force imbalance at the luminal-endothelial cell interface can lead to the deregulation of membrane shape and vessel malformation. One focus in this group grant is to collaborate with Group B01-1 to model how endothelial cells integrate haemodynamic forces and intracellular forces produced by actomyosin network to control vessel morphology and diameter. Other interests in my lab include deciphering how haemodynamic forces are sensed and transduced to alter endothelial cell behaviours; cellular mechanism(s) of developmental vessel constriction; and how cortical actin remodelling modulates membrane dynamics to shape endothelial cells.

経歴

Li-Kun studied Pharmacology as an undergraduate student at the University of Bristol, UK, and completed her Masters in Life Science at the University of Edinburgh. She obtained her Ph.D. from University College London in 2009, for her work on the role of Notch signalling in blood vessel patterning in the laboratory of Dr. Holger Gerhardt at the Cancer Research UK London Research Institute. She was awarded the EMBO and HFSP Long-term Fellowships to pursue postdoctoral research at the European Molecular Biology Laboratory (EMBL), Heidelberg in 2009, and in VIB/KU Leuven, Belgium in 2011. She next moved to the National Cerebral and Cardiovascular Center Research Institute, Osaka, in 2014, after receiving the JSPS Postdoctoral Fellowship for Foreign Researchers. She was appointed to her current position as Team Leader at RIKEN CDB/BDR in Kobe, Japan, in October 2016.

関連業績

• High-throughput imaging of blood flow reveals developmental changes in distribution patterns of hemodynamic quantities in developing zebrafish.
  Maung Ye SS, Kim KJ, Carretero NT and Phng LK
  FRONTIERS IN PHYSIOLOGY (2022)
  DOI: https://doi.org/10.3389/fphys.2022.881929
• Endothelial cell mechanics and blood flow forces in vascular morphogenesis.
  Phng LK and Belting HG.
  SEMINARS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)
  DOI: https://doi.org/10.1016/j.semcdb.2021.06.005
• Marcksl1 modulates endothelial cell mechanoresponse to haemodynamic forces to control blood vessel shape and size.
  Kondrychyn I, Kelly DJ, Taberner Carretero N, Nomori A, Kato K, Chong J, Nakajima H, Okuda S, Mochizuki N and Phng LK
  NATURE COMMUNICATIONS (2020)
  DOI: https://doi.org/10.1038/s41467-020-19308-5
• Blood flow drives lumen formation by inverse membrane blebbing during angiogenesis in vivo.
  Gebala V, Collins R, Geudens I, Phng LK* and Gerhardt H*
  NATURE CELL BIOLOGY (2016).
  DOI: https://doi.org/10.1038/ncb3320
• Formin-mediated actin polymerization at endothelial junctions is required for vessel lumen formation and stabilization.
  Phng LK, Gebala V, Bentley K, Philippides A, Wacker A, Mathivet T, Sauteur L, Stanchi S, HG Belting, Affolter M, Gerhardt H
  DEVELOPMENTAL CELL (2015).
  DOI: https://doi.org/10.1016/j.devcel.2014.11.017
• Filopodia are dispensable for endothelial tip cell guidance.
  Phng LK*, Stanchi F and Gerhardt H
  DEVELOPMENT (2013)
  DOI: https://doi.org/10.1242/dev.097352
• Nrarp coordinates endothelial Notch and Wnt signalling to control vessel density in angiogenesis.
  Phng LK, Potente M, Leslie JD, Babbage J, Nyqvist D, Lobov I, Ondr JK, Rao S, Lang RA, Thurston G, Gerhardt H
  DEVELOPMENTAL CELL (2009).
  DOI: https://doi.org/10.1016/j.devcel.2008.12.009
• Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis.
  Hellström M, Phng LK, Hofmann JJ, Wallgard E, Coultas L, Lindblom P, Alva J, Nilsson AK, Karlsson L, Gaiano N, Yoon K, Rossant J, Iruela-Arispe ML, Kalén M, Gerhardt H, Betsholtz C
  NATURE (2007)
  DOI: https://doi.org/10.1038/nature05571