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Current projects

 

The Rivero lab is investigating the role of the actin cytoskeleton and the signalling pathways that regulate its remodelling in blood platelets, small cell fragments that circulate in blood and are essential for the process of haemostasis. Haemostasis involves the formation of a plug at a site of blood vessel injury and its repair. Platelets play also roles in inflammation and infection.

 

Platelet activation is the result of multiple  signalling cascades that drive the morphological changes required for adhesion, spreading, aggregation and secretion at the sites of vascular damage. Those signalling pathways ultimately drive remodelling of the platelet cytoskeleton. Platelets constitute an excellent object for signalling studies, as responses can be monitored in terms of shape change, aggregation and adhesion, and there is a wide collection of pharmacological tools to target particular signalling pathways. Because platelets have no nucleus, there is no interference by changes in gene expression. Although for the same reason these cells cannot be genetically manipulated, but the increasing availability of mouse models has resulted in renewed interest in addressing the actin cytoskeleton in platelets.

 

My lab is applying the expertise on the actin cytoskeleton and Rho GTPases gained in various models systems in the last 20 years to address the role of two proteins, the cyclase associated protein  and coronin 1a in blood platelet function. We complement these studies with work in nucleated mammalian cell lines. The aim of our work is to help us identify the specific roles of the proteins that regulate platelet function and to evaluate their potential as targets for the development of new antiplatelet drugs that could reduce/prevent heart attacks and strokes.

 

Why is it important?

 

Cardiovascular diseases (CVD) constitute the leading cause of death worldwide. In Europe CVD accounts for 47% of all annual deaths, which amounts to over 4 million deaths per year. Similarly, in the UK CVD causes more than a quarter of all deaths, accounting for more than 161,000 people each year.

 

CVD inflicts a significant health and financial burden in terms of premature death, lost productivity, hospital treatment and prescriptions that is estimated at £19 billion in the UK. Thrombosis is a major component of the pathology that underlies CVD. Thrombosis is the formation of a blood clot within the blood vessel that can lead to occlusion of the vessel and starve the tissues and organs of oxygen and nutrients and result in myocardial infarction (heart attack) and brain infarction (stroke).

 

Anti-platelet drugs are critical for reducing adverse cardiovascular conditions in high-risk patients. However, current therapies frequently have significant side effects such as increased bleeding and haemorrhage.  More effective and specific anti-thrombotic treatments continue to be required to treat and prevent thrombosis. Precise knowledge about how platelets work is essential for the development of effective, specific and safe treatments.

 

In simple terms...

 

Platelets (thrombocytes) are small, disc shaped cell fragments. They circulate in the blood and are involved in preventing blood loss. When a vessel is injured, platelets become activated. They attach to the site of injury, stick to each other and form a plug. This process is called haemostasisUnder certain conditions a blood clot (thrombus) may form in the body even when a blood vessel is not injured. This phenomenon is called thrombosis.

 A thrombus can reduce the blood supply to an organ and cause an infarction.This is what happens during a heart attack or a stroke. These are conditions that kill millions of people every year and cost billions of pounds.

 

Several antithrombotic treatments target platelets to prevent their activation. In order to develop more efficient antiplatelet drugs, we need to know more about the mechanisms that platelets use when they activate.

 

We are specifically interested in a group of proteins that are responsible for the shape changes and the aggregation of platelets. These proteins constitute the cytoskeleton. We want to know how the cytoskeleton behaves when the platelets are quiet and once they become activated.

 

 

Our supporters

 

 

 

British Heart Foundation

 

 

 

 

 

 

The Hull York Medical School

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