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Young Investigator Awards for outstanding publications

These annual EAS prizes for young scientists are intended to recognise distinction shown by publications that contribute to the advancement of knowledge in the field of atherosclerosis and linked metabolic disturbances.

Each prize is of € 2,000. 

The winners of the annual Young Investigator Awards for outstanding publications during 2019

Basic Science Award

  • Article: Apolipoprotein C3 induces inflammation and organ damage by alternative inflammasome activation.
  • Published in: Nature Immunology. https://www.nature.com/articles/s41590-019-0548-1
  • Author: Thimoteus Speer

Clinical Science Award

  • Article: A common variant in CCDC93 protects against myocardial infarction and cardiovascular mortality by regulating endosomal trafficking of low-density lipoprotein receptor.
  • Published in: European Heart Journal. 2019 Oct 19. pii: ehz727. doi: 10.1093/eurheartj/ehz727
  • Authors (joint first authors): Antoine Rimbert and Nawar Dalila
The Award winners (from left) Timo Speer, Antoine Rimbert and Nawar Dalila

About the winners and their papers

The Basic Science winner, Timo Speer, was born 1981 in Zweibrücken, Germany. He is Head of Experimental and Translational Nephrology at Sarland University in Homburg, Germany. He has a longstanding translational interest in the importance of lipid biology for inflammatory mechanisms in cardiovascular and renal diseases. His strength is to bring together cutting edge technologies and scientists from basic science, genetics, lipidology, cardiology, immunology and his home-base, nephrology.

The data in his Award-winning paper reveal a novel and important link between triglyceride-rich lipoproteins and vascular inflammation. Using molecular methodology, animal models and human studies, Timo Speer´s paper shows that apolipoprotein C3 (ApoC3) activates the NLRP3 inflammasome in human monocytes by inducing an alternative NLRP3 inflammasome via caspase-8 and dimerization of Toll-like receptors 2 and 4. Alternative inflammasome activation in human monocytes is mediated by the Toll-like receptor adapter protein SCIMP. This triggers Lyn/Syk-dependent calcium entry and the production of reactive oxygen species, leading to activation of caspase-8. In humanized mouse models, ApoC3 activated human monocytes in vivo to impede endothelial regeneration and promote kidney injury in an NLRP3- and caspase-8-dependent manner.

These data provide new insights into the regulation of the NLRP3 inflammasome and the pathophysiological role of triglyceride-rich lipoproteins containing ApoC3. As potential clinical consequence, Timo Speer's work suggests that targeting ApoC3 might prevent organ damage and provide an anti-inflammatory treatment for vascular and kidney diseases.

The Clinical Science award-winning paper, with joint first authors Antoine Rimbert and Nawar Dalila, is on the subject of an intracellular process - almost exclusively studied by cellular biologists to date - in regulating plasma lipid levels and its effects on atherosclerosis in humans. The results show for the first time that endosomal recycling of lipoprotein receptors in the liver affects plasma levels of cholesterol and thereby risk of myocardial infarction and cardiovascular morbidity. 

The first authors of this study have been mutually dependent on making this study possible.

Acknowledgement and thanks

The Society is grateful to the members of the Award Committee, Chaired by Prof Petri Kovanen & Prof Christoph Binder, and additional reviewers who gave their time and expertise in the review and evaluation of the nominations received for these awards. There were many nominations of a very high standard - an encouraging sign for the future of research in the field!

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