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    Alain Chion, PhD

    Postdoctoral
    RCSI
    Dublin, Dublin, Ireland

    Dr Alain Chion
    Von Willebrand Factor, FVII & ADAMTS-13 diseases biology
    Royal College of Surgeons In Ireland

    Currently studying clearance mechanisms of von Willebrand Factor. Macrophage Scavenger receptor LRP1 is a major regulator of VWF levels1,2. I have found that most critical LRP1 binding sites are located in VWFA13,4. I have also identified which Lys residues are the most important for binding LRP1.
    Previous findings have unveiled the role of N-linked glycans in VWFA2 in preventing cleavage of VWF by ADAMTS-135. I have showed the same N-glycans in VWFA2 also protect VWF from accelerated clearance via LRP12; therefore integrity of N-glycans in VWFA2 seems essential for VWF homeostasis .

    I have predicted that calcium chelation in ADAMTS-13 metalloprotease domain has a functional role6. Calcium putatively shapes substrate interacting loops forming high affinity binding sites6. Recent crystal structure of ADAMTS-13 confirmed the role of calcium in the metalloprotease7.
    My other previous works showed that ADAMTS-13 binds to VWF in the D4 region away from the cleavage site in VWFA28. The physiological role of that remote binding site is still not fully understood.

    1: Rastegarlari et al BLOOD 119 (2012) 2126
    2: Chion et al. BLOOD 128 (2016) 1958
    3: Chion et al. RPTH 3 (S1)(2019) 1
    4: Wohner et al. JTH 13 (2015) 815
    5: McKinnon, Chion et al 111 BLOOD (2008) 3042
    6: Gardner, Chion et al 113 BLOOD (2009) 1149
    7: Petri et al Nat Commun 10 (2019) 3781
    8: Zanardelli, Chion et al 114 BLOOD (2009) 28199

    Presentation(s):