PhD defence: Viribus unitis - the molecular synergism between coagulation factors VIII and IX

Coagulation is the process that results in the stop of blood loss from a damaged vessel. One important protein complex in coagulation is formed by activated Factor VIII (FVIIIa) and activated Factor IX (FIXa). The importance of these two proteins is critical since their functional absence leads to the life-threatening bleeding disorders Hemophilia A or B. In this thesis, through an integrative biochemical approach, we aim to increase our understanding of the FIXa-FVIIIa complex focusing on their structure and the nature of their interactions.

Results of our studies include the discovery of unique elements important for FVIII life-cycle. We also explored the mechanisms of activation of FVIIIa and its binding to FIXa. This led to the identification of a previously unidentified region important for binding to FIXa. A comprehensive view of the structural regions of FIXa important for its function have been further identified.

Our study provides a deeper knowledge on the FIXa-FVIIIa complex and aims to assist the development of therapeutics for patients suffering from bleeding disorders.