Bierings lab

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.

Orchestration of Primary Hemostasis by Platelet and Endothelial Lysosome-Related Organelles. Karampini E, Bierings R, Voorberg J. 
Arterioscler Thromb Vasc Biol. 2020 May 7
https://pubmed.ncbi.nlm.nih.gov/32375545/

Sec22b Determines Weibel-Palade Body Length by Controlling Anterograde ER-Golgi Transport. Karampini E, Bürgisser PE, Olins J, Mulder AA, Jost CR, Geerts D, Voorberg J, Bierings R.
Haematalogica. 2020 Mar 26
https://www.ncbi.nlm.nih.gov/pubmed/32336681

Alternative Trafficking of Weibel-Palade Body Proteins in CRISPR/Cas9-engineered Von Willebrand Factor-Deficient Blood Outgrowth Endothelial Cells. Schillemans M, Kat M, Westeneng J, Gangaev A, Hofman M, Nota B, Van Alphen FPJ, De Boer M, van den Biggelaar M, Margadant C, Voorberg J, Bierings R.
Res Pract Thromb Haemost. 2019 Aug 1
https://www.ncbi.nlm.nih.gov/pubmed/31624792

Defective AP-3-dependent VAMP8 trafficking impairs Weibel-Palade body exocytosis in Hermansky-Pudlak Syndrome type 2 blood outgrowth endothelial cells. Karampini E, Schillemans M, Hofman M, van Alphen F, de Boer M, Kuijpers TW, van den Biggelaar M, Voorberg J, Bierings R.
Haematologica. 2019 Jan 10
https://www.ncbi.nlm.nih.gov/pubmed/30630984

Synaptotagmin 5 regulates Ca2+-dependent Weibel-Palade body exocytosis in human endothelial cells. Lenzi C, Stevens J, Osborn D, Hannah MJ, Bierings R, Carter T.
J Cell Sci. 2019 Feb 15;132(5)
https://www.ncbi.nlm.nih.gov/pubmed/30659119

Exocytosis of Weibel-Palade bodies: how to unpack a vascular emergency kit. Schillemans M, Karampini E, Kat M, Bierings R.
J Thromb Haemost. 2019 Jan;17(1):6-18.
https://www.ncbi.nlm.nih.gov/pubmed/30375718

Weibel-Palade Body Localized Syntaxin-3 Modulates Von Willebrand Factor Secretion From Endothelial Cells. 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, Bierings R.
Arterioscler Thromb Vasc Biol. 2018 Jul;38(7):1549-1561.
https://www.ncbi.nlm.nih.gov/pubmed/29880488

Is there more than one way to unpack a Weibel-Palade body?
Conte IL, Cookson E, Hellen N, Bierings R, Mashanov G, Carter T.
Blood. 2015 Oct 29;126(18):2165-7
https://www.ncbi.nlm.nih.gov/pubmed/26377598

STXBP1 promotes Weibel-Palade body exocytosis through its interaction with the Rab27A effector Slp4-a. van Breevoort D, Snijders AP, Hellen N, Weckhuysen S, van Hooren KW, Eikenboom J, Valentijn K, Fernandez-Borja M, Ceulemans B, De Jonghe P, Voorberg J, Hannah M, Carter T, Bierings R.
Blood. 2014 May 15;123(20):3185-94.
https://www.ncbi.nlm.nih.gov/pubmed/24700782

The interplay between the Rab27A effectors Slp4-a and MyRIP controls hormone-evoked Weibel-Palade body exocytosis.
Bierings R, Hellen N, Kiskin N, Knipe L, Fonseca AV, Patel B, Meli A, Rose M, Hannah MJ, Carter T.
Blood. 2012 Sep 27;120(13):2757-67.
https://www.ncbi.nlm.nih.gov/pubmed/22898601

The Epac-Rap1 signaling pathway controls cAMP-mediated exocytosis of Weibel-Palade bodies in endothelial cells.
van Hooren KW, van Agtmaal EL, Fernandez-Borja M, van Mourik JA, Voorberg J, Bierings R.
J Biol Chem. 2012 Jul 13;287(29):24713-20.
https://www.ncbi.nlm.nih.gov/pubmed/22511766

External collaborations:

• Prof. dr. Tom Carter (St. George's Universitiy London, United Kingdom)
• Prof. dr. Jan Voorberg (Sanquin Research and Landsteiner Laboratory, Amsterdam)
• Dr. Coert Margadant (Sanquin Research and Landsteiner Laboratory, Amsterdam)
• Prof. dr. Bram Koster (Leiden University Medical Center and Netherlands Centre for Elecontron Nanoscopy, Leiden)
• Prof. dr. Jeroen Eikenboom (Leiden University Medical Center, Leiden)
• SYMPHONY consortium "Orchestrating personalised treatment for patients with bleeding disorders"

• Landsteiner Stichting voor Bloedtransfusie Research (LSBR)
• Trombosestichting Nederland (TSN, Dutch Thrombosis Foundation)
• NWO Nationale Wetenschapsagenda (NWA)

• Ruben Bierings, principal investigator
• Petra Burgisser, research technician
• Iris van Moort, postdoc
• Marije Kat, PhD student (Sanquin)
• Sebastiaan Laan, PhD student (LUMC)