Super high-frequency multi-omics and ultrasensitive point-of-care testing towards a molecular classification of acute stroke

Ziel

Patients with acute stroke experience sudden, debilitating symptoms such as loss of speech or motor function, with an estimated loss of 100 million neurons per hour. Beyond recanalization therapy–available to only a minority of cases–our ability to intervene is limited by large gaps in our understanding of human stroke biology. Despite promising experimental insights, few mechanisms or treatments have been successfully translated into clinical practice. This particularly applies to the acute phase when the initial ischemic core evolves into the final infarct and cytoprotective strategies would have greatest impact yet have yielded neutral trial results. With SURPASS, I aim to map human stroke biology at an unprecedented molecular depth and temporal resolution to advance clinical care. By leveraging a combination of deep profiling, ultrasensitive single-molecule detection methods, and highly complementary, multi-national cohorts, I will define clinically relevant molecular signatures for acute stroke across all stages of biomarker development. Specifically, I will: i) discover novel biomarkers by exploring the global circulating proteome and metabolome at hourly resolution within the critical first 48 hours of stroke, when most neurons die, ii) validate and extend these findings in independent, large cohorts, including a global clinical trial, and iii) translate into clinical practice by establishing ultrasensitive point-of-care testing for continuous monitoring of brain injury using DNA-origami-based nanoparticles. By linking serial molecular data with longitudinal neuroimaging and deep clinical phenotyping, I will determine molecular signatures for outcome-relevant mechanisms that allow to stratify patients across biological stroke subtypes, ultimately developing a molecular classification of stroke with therapeutic implications. SURPASS will transform our conceptualization of human acute ischemic stroke, bridge the translational gap, and improve patient care.

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