PI Johan Björkegren, Department of Medical Physics and Biochemistry

1. DNA-on/DNA-off—towards biomarkers predicting molecular disease states driving coronary artery disease in subgroups of patients PI Johan Björkegren, Department of Medical Physics and Biochemistry Objectives Identify easily obtainable DNA/RNA/protein biomarkers to detect causal molecular activity in CAD and to use these biomarkers for early diagnosis of CAD, subdivide CAD patient based on their molecular disease status and evaluate novel drugs against CAD costumed to given patient subgroups • Sequencing 1400 RNA samples (including microRNA) of whole blood and s.c. fat and screen 500 tracer proteins in 700 plasma samples of the STARNET cohort. • Computational identification of biomarkers from generated datasets predicting disease states in and across CAD relevant organs. • Evaluation of selected sets of biomarkers in healthy CAD-risk individuals and additional CAD patients for longitudinal observations (primary endpoints CAD morbidities and mortality) and during disease development in relevant mouse models of CAD. • Use selected sets of biomarkers for compound evaluations to evaluate; i) target engagement ii) compound pathophysiological effects reflected by network activity (i.e. proof of mechanisms/principal) and iii) compound effect on CAD (i.e. proof of concept). Clinical cohorts Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) study 600 CAD patients with DNA, RNA from 8 tissues, blood and full clinical characterisation, 100 nonCAD controls, further recruitment ongoing Technologies DNA/RNA/protein profiling, clinical and preclinical models AZ contributions Maria Lagerström-Fermér (CVGI), Magnus Ivarsson (TSC)