HON ondersteunt Jingnan Huang met € 500,- voor proefschrift
Mede dankzij Hart Onderzoek Nederland heeft Jingnan Huang haar proefschrift kunnen voltooien.
Jingnan vertelt over haar proefschrift:
Platelet proteomic progress and retraining mechanisms in glycoprotein VI-mediated thrombus formation
Cardiovascular diseases (CVD) are among the greatest threatens to human health, platelets play a key role in the onset and establishment of arterial thrombus formation, whereas they are also crucial for normal hemostasis. Glycoprotein VI (GPVI) is the major signaling collagen receptor on the surface of platelets, which is known to induce thrombus formation by binding to collagen directly, or binding to fibrin in second instance. In GP6-deficient mouse, only a moderate increase of the bleeding time was observed, while arterial thrombosis was substantially impaired. This crucial role of GPVI in arterial thrombosis with limited influence on hemostasis makes GPVI to a novel potential antithrombotic target. Therefore, this thesis on human platelets aims to contribute to the support for a selective antithrombotic effect of GPVI signaling inhibition or blockage.
In my thesis, I provided a comprehensive overview of the complete platelet proteome and revealed the full composition of platelet proteome by a global comparison of platelet proteomes and transcriptomes. The generated large datasets – also to compare human and mouse platelets – can now be used to elucidate the mechanisms of GPVI-induced thrombus formation, and ultimately for determining protein targets downstream of GPVI for use in the clinic. In addition, I investigated signaling pathways that were thought to enhance or restrain the GPVI-induced platelet activation and thrombus formation, pointed to a partial overlap of the clinical-relevant antagonism of GPVI and αIIbβ3 and a shear-dependent role of PTK2, CIB1 and integrin αIIbβ3 in collagen- and GPVI-mediated platelet activation and thrombus formation.
Overall, this thesis provides a powerful tool for further investigating the platelet protein composition and to reveal the relations of the platelet proteome and transcriptome across human and mouse. In addition, this thesis provides novel insights into the precise regulation and mechanism of the GPVI-mediated signaling and thrombus formation. There is still a new avenue to open by mass-spectrometry based proteomics methods, also to help further elucidating the positive and negative pathways underlying GPVI-induced thrombus formation in hemostasis and thrombosis; and furthermore to help identifying GPVI antagonist, such as developed in the H2020 TAPAS program for antithrombotic studies.