Dr. Margaret Lucitt

Summary

Platelets play a major role in both haemostasis and thrombosis (1). Although under healthy homeostatic conditions these anucleate cell derivatives of bone marrow megakaryocytes are relatively inert and short lived, they become rapidly activated upon exposure at sites of vascular injury and inflammation, whereupon they are transformed into highly adherent bodies and play a central role in primary haemostasis through the development of a 'platelet plug'. As such, platelets, and in particular the pathways, which regulate their activation, are critically important in the context of atherosclerotic diseases such as myocardial infarction and stroke. Thrombotic clot formation is a dynamic three-stage process with initiation, extension and stabilization phases. Recent data has defined the role for molecules in thrombus stability such as the Eph receptor tyrosine kinases(2), Semaphorin 4D(3) and Gas 6(4). Other molecules which support thrombus stability include the CTX family such as the junctional adhesional molecules (JAM-A and JAM-C)(5). Despite significant advances in our understanding of platelet biology, many platelet cell surface proteins have been identified whose function remains undetermined, but may exert an important role in platelet behaviour (6). This proposal aims to define the function of one such protein, CD226 (DNAM-1), a member of the CTX family, is a cell surface protein with 2 Ig extracellular domains, a single transmembrane domain and a cytoplasmic tail (7). Our preliminary data strongly suggests that DNAM-1 has a novel functional role in platelet aggregation and hence thrombus formation. The study has two specific aims; 1) To characterise the functional role of DNAM-1 on platelets and 2) To investigate DNAM-1 related signalling events in platelets.

Funding Agency

Haematology association of Ireland

Project Type

HAI Novartis Fellowship 2015

Summary

Calcium supplementation agents are the 8th most prescribed product under the general medical card scheme in Ireland. While these agents are overwhelmingly prescribed to promote bone health, there is accumulating evidence to indicate that they may also have more wide ranging health benefits. AquaminTM is a natural multi-mineral complex, which contains calcium as its major component. AquaminTM supplements, known to improve bone health, may also exhibit cardioprotective effects through its lipid lowering and anti-inflammatory properties. Here we aim to investigate the role of AquaminTM supplementation on the pathogenesis of metabolic and cardiovascular disease in vivo using established preclinical models of disease (Aim1), while also investigating the precise mechanisms through which AquaminTM modulates inflammation in the context of metabolic dysfunction and consequent atherosclerosis (Aim2)

Funding Agency

Marigot Ltd Industry Research Collaboration 2018

Project Type

Industry Partnership

Summary

The studies outlined in this proposal are aimed at investigating a biological pathway which may play an important role in driving the development of psoriasis among obese patients. Based upon new discoveries we have identified a protein known as IL-36 which is elevated among obese individuals and is emerging as an important orchestrator of skin inflammation in psoriasis. We will evaluate whether IL-36 plays a critical linking role in driving psoriasis among obese individuals and dermine whether blocking its activity represents a new therapeutic strategy for treating these patients.

Funding Agency

Health Research Board

Programme

Investigator-Led Projects 2019