Scientists unveil molecular map that could unlock new treatments for heart and lung diseases

Posted on: 07 April 2026

The study, which was led by an international team including researchers from Trinity and published in leading international journal, Nature Communications, used advanced cryo-electron microscopy to capture high-res images of the “thromboxane A₂ receptor ” while it was active and primed to send signals across the membrane to the cell interior. 

This receptor is found on blood platelets and many other cell types, where it helps regulate blood clot formation, blood vessel contraction, and inflammatory responses. 

“Thromboxane A₂ itself is a short-lived signalling molecule that disappears within seconds in the body, which has always made it difficult for us to study how it activates the receptor,” said Dr Pawel Krawinski, Postdoctoral Research Fellow in Trinity’s School of Medicine and School of Biochemistry and Immunology. 

“To overcome this, we used a new technique which allowed us to visualise its structure in extraordinary detail and that in turn helped us learn how it interacts with signalling proteins inside the cell.” 

The structural images from their work revealed several surprising features. It turns out that unlike many related receptors, the thromboxane receptor uses an unusual “activation switch” that triggers internal signalling.

And the researchers also discovered signalling molecules likely enter the receptor from within the cell membrane, rather than from outside the cell. 

Dr Krawinski added: “These insights are fascinating to us, but they are far more than just structural details as they could have important medical implications too. The thromboxane receptor plays a role in multiple diseases, including cardiovascular and cardiopulmonary disorders, pulmonary arterial hypertension, and fibrotic lung disease. It is also overactive in some cancers and inflammatory conditions. 

“By revealing exactly how activating molecules bind and trigger the receptor, the new molecular map provides a blueprint for developing drugs that can selectively block or fine-tune its activity. Such drugs could help prevent harmful blood clotting, reduce excessive blood vessel constriction, or limit inflammatory signalling linked to disease.”

The study also sheds light on rare inherited mutations in the receptor that cause bleeding disorders. Understanding how these mutations alter the receptor’s structure may help researchers better diagnose and treat patients with these conditions. 

What are the potential implications of this research?

Overall, the research offers an unprecedented view of a clinically important signalling system. By combining structural biology, computational modelling, and laboratory experiments, the team has provided a detailed molecular map that could guide the design of safer and more effective therapies targeting the thromboxane receptor in the future.

This work was supported by funding from Research Ireland, the European Research Council, the Blavatnik Foundation, the Zuckerman STEM Leadership Program, and the Biotechnology and Biological Sciences Research Council. 

The study can be read on the Nature Communications website. 

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