Speaker: Dr. Danica Stanimirovic Director, Neurobiology Program at the Institute for Biological Sciences, National Research Council of Canada, Canada Discovery to Diagnostics: Using In Vivo Molecular Imaging as Biomarker Validation Paradigm Application of genomics and proteomics technologies in the discovery process has resulted in the explosion of potential biomarkers and targets for detecting/treating brain diseases; yet, the process of validation of these biomarkers has stumbled upon extraordinary complexity of brain diseases and translation into clinical environment has not materialized. Here, we will present a biomarker discovery-validation paradigm that links genomics and proteomics discovery workflows with the development of molecular imaging agents against selected targets and their validation in vivo by non-invasive imaging. Discovery workflows include laser-capture microdissection of target brain tissues from animals or humans coupled to microarray transcriptional profiling or quantitative proteomics (ICAT or label free), followed by target prioritization in silico using bioinformatics tools for data mining and literature analyses. Further target selection is based on confirmatory validation of prioritized targets in tissue sections and their ‘accessibility’ for targeting moieties. Single-domain antibody (sdAb) platform is then used to isolate binding/modifying antibodies against selected targets; given their small size (13kD), ease of expression and engineering, targeting sdAbs were subsequently engineered to carry imaging contrast agent(s) directly or in the context on nano-carriers to the target site. The biomarker/target validation in vivo was then achieved by non-invasive in vivo imaging enabling prospective analyses of target expression during the course of disease or disease treatment, and linking the target/biomarker to disease outcomes. The talk will present examples of application of this discovery-validation paradigm in brain tumors and stroke and in the development of integrated molecular imaging/brain drug delivery strategies.