Lazaros Belbasis

Research project title:  Identifying potential drug targets and causal pathways for ischemic stroke using proteomic and genomic data

Research summary

The main objective of my research project is to identify of plasma proteins associated with ischaemic stroke and its subtypes. To achieve this, I apply the Mendelian randomisation approach, which is an instrumental variable technique that leverages genetic variants as proxies for exposures, such as plasma protein levels. Recent technological advances enable the measurement of thousands of proteins in large-scale population biobanks. Genome-wide association studies can then use these data to identify protein quantitative trait loci, which can serve as instrumental variables to proxy plasma protein levels within the Mendelian randomisation framework and estimate the potentially causal impact of plasma proteins on ischaemic stroke.

Additionally, my project aims to explore the role of traditional risk factors of ischaemic stroke. By integrating genetic and proteomic data into a Mendelian randomisation framework, I investigate how plasma proteins may mediate the effects of these risk factors. This comprehensive approach uncovers potential additional therapeutic targets and clarifies the underlying mechanisms contributing to stroke development.

Ischaemic stroke remains a leading cause of morbidity and mortality worldwide, with a rising burden that highlights the need for novel therapeutic strategies. Plasma proteins play a crucial role in numerous biological processes. By identifying proteins related to ischaemic stroke, we can uncover potential drug targets and gain insights into the molecular pathways that contribute to ischaemic stroke. Recent advances in proteomics, particularly through data from large population biobanks, present an unprecedented opportunity to explore the role of the plasma proteome in chronic diseases, such as ischaemic stroke. However, observational studies are often limited by biases, which could be overcome by combining genetic data with Mendelian randomisation to derive more robust causal conclusions.

My fellowship is supported by two leading experts at the Nuffield Department of Population Health. Prof Jemma C. Hopewell has an expertise on leveraging genetic and clinical trial data to advance precision medicine and identify drug targets in cardiovascular diseases. Prof Cornelia van Duijn brings expertise in the integration of multiple –omics data to study molecular pathways for chronic diseases. Their combined guidance perfectly aligns with my research goals, enabling me to explore the molecular determinants of ischaemic stroke.