A Systems Medicine approach to understand, re-classify and treat chronic inflammatory diseases in a personalized way

Timothy Radstake MD, PhD has joined the UMC Utrecht in 2012 as professor of Translational Immunology within the departments of Rheumatology & Clinical Immunology and on the Laboratory of Translational Immunology. After receiving his MD (2000) and PhD (2003) (Prof. W.B. van dan Berg / Prof. P.L.C.M. van Riel) he started his clinical training as rheumatologist and simultaneously started up his own research group on the role of genetic factors and dendritic cells in inflammatory diseases. From 2007 – 2008 he did a post-doctoral fellowship at the Scleroderma Centre of the Boston University School of Medicine (Prof. R. Lafyatis) from where he started the research line to decipher the role of the immune system in Scleroderma and other chronic inflammatory diseases.

With the aim to overcome the “valley of death” in medical sciences and to be able to truly achieve personalized medicine he started the Utrecht Systems Medicine initiative. Today this has resulted into establishing a cohort comprising > 25.000 patients with an Immune mediated inflammatory Disease (IMID). From a substantial part of these patients five cell subsets (monocytes, T cell, B cells, myeloid- and plasmacytoid dendritic cells) are isolated and analysed for several OMICs layers including extensive flow cytometry, transcriptomics (RNA seq), epigenomics (MiRNA, Histon landscape, lnRNAs), metabolomics and proteomics. Next to genome wide integration of these cellular layers, information on the circulating metabolome, proteome, lipidome and microbiota of the gut, oral cavity and / or skin is integrated into a so-called patient specific immune network with the purpose of identifying patient specific causative molecular pathways but also allowing in silico analysis of early drug candidates thereby truly embarking n stratified medicine. With a lab comprising ~ 45 fte on molecular biology, translational research, computational biology and clinician researchers covering the field of Rheumatology, Dermatology, Gastroenterology and Ophthalmology this ensures a truly cross-disciplinary approach overcoming the usual diagnostic hurdles of patients with IMIDs.

During my presentation I will embark on the successes that Systems Medicine have given my group in the understanding of complex immune networks leading to disease and will explain why and how integration of multiple data layers from immune cell subsets from patients with IMIDs will revolutionize our view and possibilities with regard to therapeutic targeting in the near future.