UCD Conway SPHERE is an interdisciplinary research group where people with a diverse range of skills are working on numerous projects with common themes throughout. Below is a list of the current, ongoing projects within our group.
The PALADINTM platform
The UCD Conway SPHERE team (Lead RPO) have developed a new blood-based innovative diagnostics platform PALADINTM (PlAteLet bAsed DIagNostics) that captures the power of the platelet releasate and uses advanced proteomics methods, state-of-the-art equipment and artificial intelligence to uncover useful molecular diagnostics for chronic disease. PALADINTM addresses the unmet need for an easily accessible, minimally invasive source for high-quality specific molecular biomarkers in numerous diseases. In contrary to most often used biofluids with very high dynamic range such as plasma or serum, PALADINTM harnesses the power of platelets which act as a natural ‘sieve’ and pick out important messages. Therefore, by analysing the platelet releasate the problem of highly abundant plasma proteins is resolved.
EXCLAIM study (EnoXaparin modulation of CoaguLAtion and InflaMmation in patients with elevated BMI)
Enoxaparin is one of the most widely used LMWHs for the prevention of hospital-acquired VTE (HA-VTE). It has well established anticoagulant and anti-inflammatory properties and has been shown to reduce the incidence of HA- VTE. However, obesity (a well-established risk factor for HA-VTE) influences the anticoagulant and anti-inflammatory activity of enoxaparin but the mechanisms remain unknown. The inadequate anticoagulation in the morbidly obese is frequently attributed to a weight issue, however, obesity is a complex metabolic syndrome associated with major changes in numerous physiologic systems. The EXCLAIM study aims to determine if morbidly obese patients receiving enoxaparin thrombophylaxis display inadequate anticoagulant responses across multiple assays of coagulation. Furthermore, the study will assess if obesity influences the anti-inflammatory properties of enoxaparin as well as its anticoagulant activity. Finally, we aim to determine if baseline markers of coagulation, inflammation, renal and hepatic function, as well as body weight influence response to enoxaparin thrombophylaxis in obese individuals.
Rivaroxaban is a direct oral anticoagulant that has similar efficacy to warfarin in management of non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE) and is currently prescribed in preference to warfarin. Rivaroxaban inhibits activated factor X (FXa), which converts prothrombin to thrombin. However, thrombin and FXa also mediate pro-inflammatory signalling, leading to further activation of coagulation. Recent studies revealed that Rivaroxaban downregulated pro-inflammatory protein expression and reduced complement activation, while warfarin failed to do so. Therefore, long-term inhibition of FXa may confer additional benefits that are unrelated to Rivaroxaban’s anticoagulant function but rather, are mediated by inhibition of pro-inflammatory signalling. Extracellular vesicles (EVs) are pro-inflammatory mediators that regulate many physiological and pathological processes. It is likely that the well-characterized anti-inflammatory effects of Rivaroxaban will be mirrored by similar effects upon plasma EVs. The RIVEVE study aims to characterize the influence of Rivaroxaban upon circulating pro-inflammatory EVs using a combination of single vesicle analysis and proteomics.
CAPE study (Coagulation Activation in PreEclampsia)
Preeclampsia (defined as new hypertension presenting after 20 weeks gestation with significant proteinuria) is a serious complication of pregnancy with potentially life-threatening consequences for both mother and baby. It is a major public health issue and a leading cause of death in the UK/Ireland. At present, preeclampsia diagnosis relies on error-prone techniques, furthermore the delivery of the preterm infant is the only curative treatment. However, preterm delivery is associated with significant risk of foetal morbidity and mortality, especially in preterm births and even minor improvements in length of gestation at delivery confer significant survival benefits, therefore every day in utero counts. Using the PALADINTM platform, we have discovered candidate biomarkers that distinguish patients with preeclampsia from healthy pregnant women and that have the potential to calculate the risk of developing severe preeclampsia and whose preterm delivery can be delayed. Currently we are working on translating this research to an easier to use, plasma-based platform.
Multiple Sclerosis study
Multiple sclerosis is an inflammatory neurodegenerative disease of the central nervous system affecting over 2.3 million people worldwide. The progression of multiple sclerosis can differ among patients. Majority of patients suffer from relapsing remitting multiple sclerosis where they experience episodes of severe inflammation followed by a remittance from the disease. Whereas, some patients follow a progressive disease course from the outset and are classified as primary progressive multiple sclerosis. The complex aetiology of multiple sclerosis and the diverse symptoms make a definite diagnosis challenging. Multiple sclerosis is diagnosed by a combination of clinical attacks and lesions observed by MRI therefore the diagnosis can be prolonged in time and it is often hard to distinguish between disease types at the early stages of diagnostic process. Using the PALADINTM platform and ELISA, we have discovered candidate biomarkers capable of aiding the diagnosis of multiple sclerosis and distinguishing patients with relapsing remitting from primary progressive disease. Currently, we are assessing platelet-specific biomarkers and proteins we have discovered in multiple sclerosis patients and how these can be utilised as predictors for disease progression in patients.
We are delighted to have a variety of funders and sponsors both from state bodies and from industry and we thank them for their continued support.