Integrative analysis of omics data from experimental and clinical sepsis in a translational approach towards individualized prevention, diagnosis and therapy
Acronym: TransSeptomics (Translational Septomics)
Principal Investigator: Sandro Lambeck, PhD
Research Area: B Novel Diagnostic Tools and Approaches
Project Number: B3.4
Duration: 01.07.2011 bis 01.07.2013
Module: Start-up Scientist
The Problem
Understanding the molecular mechanisms involved in the pathophysiology of sepsis facilitates the optimization of clinical practice. The project aims to find diagnostic and therapeutic markers by analyzing high-throughput data comprising transcriptomic and metabolomic measurements obtained from animals and patients in a systems biology approach.
Results so far
Robust methods for the unbiased analysis of multidimensional data were developed and applied to the host response in experimental and clinical sepsis (ICU). Pneumonia-specific features, comprising an orchestrated hepatic response of transcripts and effectors along cholesterol metabolism, were identified and experimentally confirmed by interventional attenuation of severity in murine models. In addition, signatures for fibrosis and cholestasis, relevant sequelae of sepsis, could be determined in rodent peritonitis (PCI) and validated subsequently. Common expression patterns of conserved features from the innate and adaptive immune response, comprising upregulated toll-like receptor signaling and downregulated major histocompatibility (MHC) class II genes, were detected in an inter-species comparison of microarray data in blood. Obtained candidates from these translational methods harbour diagnostic and treatment options for septic shock patients, including the individualized prediction of outcome from hydrocortisone administration or other immunomodulators.
Publications
Weber M, Lambeck S, Ding N, Henken S, Kohl M, Deigner HP, Enot DP, Igwe EI, Frappart L, Kiehntopf M, Claus RA, Kamradt T, Weih D, Vodovotz Y, Briles DE, Ogunniyi AD, Paton JC, Maus UA, Bauer M: Hepatic induction of cholesterol biosynthesis reflects a remote adaptive response to pneumococcal pneumonia. FASEB J 2012 Jun, 26(6):2424-36.
Gonnert FA, Kunisch E, Gajda M, Lambeck S, Weber M, Claus RA, Bauer M, Kinne RW: Hepatic Fibrosis in a Long-Term Murine Model of Sepsis. Shock 2012 Apr, 37(4):399-407.
Lambeck S, Weber M, Gonnert FA, Mrowka R, Bauer M. Comparison of sepsis‐induced transcriptomic changes in a murine model to clinical blood samples identifies common response patterns. Frontiers: Systems Biology of Microbial Infection. [Epub ahead of print].
Contact
Tel.: +49 (0)3641 - 9 32 33 45
Center for Sepsis Control and Care
Universitätsklinikum Jena
Erlanger Allee 101
07747 Jena