Bierings Lab
Molecular mechanisms of Von Willebrand factor secretion
Ruben (R.) Bierings
E-mail: r.bierings@erasmusmc.nl
X: @rbierings
Scopus: link
PubMed: link
LinkedIn: link
Contact:
Tessa Mannee, secretary, t.mannee@erasmusmc.nl
Ruben Bierings is an endothelial cell biologist and Associate Professor in the Department of Hematology. He received his PhD from Utrecht University for his work on Von Willebrand factor secretion in endothelial cells (2007, thesis “Sorting out the Weibel-Palade body), which was carried out at CLB-Sanquin Research in Amsterdam. He completed postdoctoral research as an MRC Career Development Fellow (2007-2011) at the National Institute for Medical research (NIMR) in London (UK). Upon his return to the Netherlands he started his own lab, first at Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, but since 2018 at Erasmus MC. He serves as a co-chair of the International Society for Thombosis and Haemostasis (ISTH) Vascular Biology Scientific Standardization Subcommittee (SSC). Research in the Bierings lab revolves around the molecular mechanisms of Von Willebrand factor secretion, biogenesis and exocytosis of Weibel-Palade bodies and how defects in these process can give rise to bleeding abnormalities in patients.
Our research
In our lab we study the molecular mechanisms of secretion in endothelial cells and platelets in order to understand how defects in these mechanism can lead to bleeding disorders.
Using innovative (patient-derived) cellular model systems such as blood outgrowth endothelial cells (BOECs) and induced pluripotent stem cells (iPS)-derived megakaryocytes we are systematically investigating the mechanisms that control how secretory organelles such as endothelial Weibel-Palade bodies (WPBs) or platelet alpha- and dense granules are formed and how they acquire the molecular machinery to undergo exocytosis.
Our team
Ruben Bierings, principal investigator
Petra Bürgisser, research technician
Iris van Moort, postdoc
Isabel Bär, PhD student
Sophie Hordijk, PhD student
Bas Laan, PhD student
Buram Ardiç, intern
Key publications
Swinkels M, Hordijk S, Bürgisser PE, Slotman JA, Carter T, Leebeek FWG, Jansen AJG, Voorberg J, and Ruben Bierings. Quantitative super-resolution imaging of platelet degranulation reveals differential release of von Willebrand factor and von Willebrand factor propeptide from alpha-granules. J. Thromb. Haemost. 2023;21(7):1967–1980.
Kat M, Karampini E, Hoogendijk AJ, Bürgisser PE, Mulder AA, Van Alphen FPJ, Olins J, Geerts D, Van den Biggelaar M, Margadant C, Voorberg J, and Ruben Bierings. Syntaxin 5 determines Weibel-Palade body size and Von Willebrand factor secretion by controlling Golgi architecture. Haematologica. 2022;2021.12.10.472050.
Kat M, Bürgisser PE, Janssen H, De Cuyper IM, Conte IL, Hume AN, Carter T, Voorberg J, Margadant C, and Ruben Bierings. GDP/GTP exchange factor MADD drives activation and recruitment of secretory Rab GTPases to Weibel-Palade bodies. Blood Adv. 2021;5(23):5116–5127.
Schillemans M, Kat M, Westeneng J, Gangaev A, Hofman M, Nota B, van Alphen FPJJ, de Boer M, van den Biggelaar M, Margadant C, Voorberg J, and Ruben Bierings. Alternative trafficking of Weibel-Palade body proteins in CRISPR/Cas9-engineered von Willebrand factor-deficient blood outgrowth endothelial cells. Res. Pract. Thromb. Haemost. 2019;3(4):718–732.
Swinkels M, Atiq F, Bürgisser PE, Slotman JA, Houtsmuller AB, de Heus C, Klumperman J, Leebeek FWG, Voorberg J, Jansen AJG, and Ruben Bierings. Quantitative 3D microscopy highlights altered von Willebrand factor α-granule storage in patients with von Willebrand disease with distinct pathogenic mechanisms. Res. Pract. Thromb. Haemost. 2021;5(6):e12595.
Karampini E, Bürgisser PE, Olins J, Mulder AA, Jost CR, Geerts D, Voorberg J, and Ruben Bierings. Sec22b determines Weibel-Palade body length by controlling anterograde ER-Golgi transport. Haematologica. 2021;106(4):1138–1147.
Karampini E, Schillemans M, Hofman M, van Alphen F, de Boer M, Kuijpers TW, van den Biggelaar M, Voorberg J, and Ruben Bierings. Defective AP-3-dependent VAMP8 trafficking impairs Weibel-Palade body exocytosis in Hermansky-Pudlak Syndrome type 2 blood outgrowth endothelial cells. Haematologica. 2019;104(10):2091–2099.
Schillemans M, Karampini E, van den Eshof BL, Gangaev A, Hofman M, van Breevoort D, Meems H, Janssen H, Mulder AA, Jost CR, Escher JC, Adam R, Carter T, Koster AJ, van den Biggelaar M, Voorberg J, and Ruben Bierings. Weibel-Palade Body Localized Syntaxin-3 Modulates Von Willebrand Factor Secretion From Endothelial Cells. Arterioscler. Thromb. Vasc. Biol. 2018;38(7):1549–1561.
Van Breevoort D, Snijders AP, Hellen N, Weckhuysen S, Van Hooren KWEMEM, Eikenboom J, Valentijn K, Fernandez-Borja M, Ceulemans B, De Jonghe P, Voorberg J, Hannah M, Carter T, and Ruben Bierings. STXBP1 promotes Weibel-Palade body exocytosis through its interaction with the Rab27A effector Slp4-a. Blood. 2014;123(20):3185–3194.
Ruben Bierings, Hellen N, Kiskin N, Knipe L, Fonseca A-V, Patel B, Meli A, Rose M, Hannah MJ, and Carter T. The interplay between the Rab27A effectors Slp4-a and MyRIP controls hormone-evoked Weibel-Palade body exocytosis. Blood. 2012;120(13):2757–2767.
Rondaij MG, Ruben Bierings, van Agtmaal EL, Gijzen KA, Sellink E, Kragt A, Ferguson SSG, Mertens K, Hannah MJ, van Mourik JA, Fernandez-Borja M, and Voorberg J. Guanine exchange factor RalGDS mediates exocytosis of Weibel-Palade bodies from endothelial cells. Blood. 2008;112(1):56–63.