The International Society on Thrombosis and Haemostasis (ISTH) announced the winners of the 2024 Fundamental Research Career Development Awards at the conference. This award aims to recognize early-career researchers who have made outstanding achievements in basic research. By acknowledging and encouraging these young scientists' innovative ideas, ISTH hopes to support them on their path to independent research, thereby strengthening the field of basic research. Each awardee will receive a grant to support their research, training, and collaborative studies in their respective fields. This award program, meticulously planned by the ISTH Fundamental Research Working Group under the guidance of the Education Committee, is designed as a career development incentive for promising early-career researchers.

Atypical Interactions in the Coagulation System: Dr. Stijn Agten

Institution: Cardiovascular Research Institute Maastricht (CARIM), Netherlands

Research Title: Coagulation meets calcification: Gla-diators as protectors of vascular integrity

Research Overview:

The family of vitamin K-dependent proteins (VKDPs), which includes Gla proteins, plays a crucial role in various physiological and pathological processes in the human body. VKDPs are essential regulators in biological processes such as coagulation, calcification, and cell proliferation. Studies have shown that the absence of VKDPs in knockout mouse models or humans can lead to embryonic lethality, accelerated aging, and even premature death. Notably, while coagulation and calcification are biologically distinct processes, VKDPs from different subfamilies significantly impact key aspects of vascular calcification. However, the specific mechanisms by which VKDPs inhibit calcification remain unclear. This research aims to explore how Gla-containing VKDPs regulate vascular calcification. The research team successfully synthesized non-carboxylated and carboxylated variants of VKDPs using chemical protein synthesis and evaluated their ability to inhibit calcium phosphate precipitation in vitro. Additionally, by adding VKDPs to cultured human vascular smooth muscle cells (hVSMCs) under calcifying conditions, the team assessed their impact on cell calcification. Detailed protein structure analyses were performed using circular dichroism and nuclear magnetic resonance (NMR) spectroscopy. Furthermore, in-depth studies were conducted on cells treated with different VKDPs using extensive RNA sequencing techniques. The study synthesized three VKDPs: matrix Gla protein (MGP), osteocalcin, and protein S Gla domain (PSGla). The results showed that carboxylation significantly affects the secondary structure of VKDPs. Non-carboxylated VKDP variants exhibited weaker activity in inhibiting in vitro calcium phosphate precipitation and hVSMC calcification. In contrast, all carboxylated variants (osteocalcin > protein S Gla > MGP) effectively inhibited in vitro biophysical calcium crystal precipitation. However, in terms of biological calcification inhibition in hVSMCs, PSGla and MGP fully inhibited calcification, but RNA sequencing revealed significant differences in gene expression in hVSMCs treated with these two VKDPs. In summary, VKDPs from the calcification and coagulation subfamilies significantly impact vascular calcification. Differences in inhibitory activity among VKDPs may reflect their distinct modes of action, corroborated by observed differences in gene expression.

Fundamental Mechanisms of Blood Coagulation: Dr. Yohei Hisada

Institution: University of North Carolina at Chapel Hill, USA

Research Title: The roles of the S100A10/annexin A2/tissue plasminogen activator and the urokinase plasminogen activator/urokinase plasminogen activator receptor pathways in the activation of fibrinolysis and bleeding in a mouse model of acute promyelocytic leukemia

Fundamental Mechanisms of Blood Coagulation: Dr. Marie Hollenhorst

Institution: Brigham and Women’s Hospital, Harvard Medical School, USA

Research Title: Establishing the platelet-intrinsic mechanisms underlying the well-known epidemiologic association between ABO blood type and risk of bleeding and clotting