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个人简介
Throughout my career, I have taken a multi-disciplinary approach, including proteomics, mouse genetics and pharmacology to elucidate novel mechanisms controlling platelet production and activation. My primary research interest is to determine how tyrosine phosphatases work in conjunction with tyrosine kinases to control the level of phosphorylation and signal transduction in platelets with the overall objective of identifying novel anti-thrombotic drug targets.
Over the past 15 years, I pioneered novel areas of research in the field of reversible phosphorylation in the megakaryocyte (MK)/platelet lineage, establishing that the receptor-type tyrosine phosphatase CD148 together with the tyrosine kinase C-terminal Src kinase (Csk) forms a ‘molecular rheostat’ controlling the level of Src family kinase (SFK) activity in MKs and platelets, and their ability to respond to their environment. I have also demonstrated that the immunoreceptor tyrosine-based inhibition motif (ITIM)-containing MK and platelet inhibitory receptor G6B (MPIG6B, G6b-B, G6B) forms an inhibitory complex with the non-transmembrane tyrosine phosphatases Shp1 and Shp2 that plays a central role in regulating the number and reactivity of platelets in the circulation. Defects in either of these mechanisms disrupts platelet homeostasis, resulting in macrothrombocytopenia, bleeding, MK expansion and myelofibrosis, similar to that observed in myeloproliferative neoplasms (MPN).
Biological functions of CD148 and G6B beyond regulating SFKs and immunoreceptor tyrosine-based activation (ITAM)-containing receptors, respectively, that are being explored. Cellular, molecular and biophysical approaches are being employed to elucidate the regulation of CD148 and G6B by heparan sulfate proteoglycans, and novel ways of targeting these receptors are being developed.
研究兴趣
论文共 122 篇作者统计合作学者相似作者
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Alexandra Mazharian, Ophélie Bertin,Amrita Sarkar, Johanna Augros, Alicia Bornert,Cécile Loubière,Friederike Jönsson,Juli Warwicker, W. Abbott Mark,Omer Dushek,Caroline Vayne,Lubica Rauova,
biorxiv(2024)
Research and Practice in Thrombosis and Haemostasispp.102386, (2024)
Research Square (Research Square) (2023)
FRONTIERS IN IMMUNOLOGY (2023): 1226196-1226196
Alexandra Yakusheva,Alexandre Slater, Bernard Payrastre,Cedric Garcia, Giorgia D'Italia,Harriet Allan,Judith M. E. M. Cosemans,Matthew Harper,Meinrad Gawaz, Paul Armstrong,Sara Troitino,Silvia Maria Grazia Trivigno,
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASISno. 7 (2023): 102140
Alexandra Yakusheva,Alexandre Slater, Bernard Payrastre,Cédric Garcia, G. D'Italia,Harriet E Allan,Judith M.E.M. Cosemans,Matthew T. Harper, Meinrad Gawaz, Paul Armstrong,Sara Troitiño,Silvia Maria Grazia Trivigno,
Research and Practice in Thrombosis and Haemostasisno. 7 (2023): 102140-102140
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