Disease Systems Biology

Infection Biology

Our group aims to overcome the challenges that currently limit the development and exploitation of novel personalized combinatorial therapies for sepsis by improving the understanding of infections and sepsis pathophysiology, developing novel approaches for the early diagnosis and optimal treatment of sepsis and sepsis-related organ failure. The specific objectives of our group are: to identify host biomarker signatures through multi-omics high-throughput analysis that would enable early diagnosis of infection and sepsis, and that can trigger early pre-symptomatic treatment; to recognize appropriate subsets of sepsis patients through integration of biological and clinical data to target with novel therapies; and to design combinatorial therapies based on in-silico pathway drug networks and validate them in preclinical and clinical studies.

Personalized diet

It is well known that nutrition is the cornerstone of an individual’s environment, as such understanding how diet influences metabolic regulation and how dietary interventions can improve health is a key scientific goal. Furthermore, diet has a major influence on the overall quality of life beyond the prevention of diseases and its role is fundamental for individual performance and enjoyment. Even though the personalized approach to diet is the logical next step – much like the transition from pharmacology to personalized medicine – this task is extraordinarily complicated. Most foods are composed of hundreds of bioactive compounds, often interacting with each other. Furthermore, the targets are of varied concentrations and different targets have different affinities and specificities. Unfortunately, nutritional trials are not designed for mechanism-based preclinical studies, and little is known about their molecular targets. Our group integrates chemoinformatics, in-silico metabolic modelling, microbiome and network biology for performing global analyses of diet that elucidates the synergistic interactions of small molecules that yield specific phenotypes and hopefully contribute towards personalized nutrition.

Staff

Albert García López
Mohammadhassan Mirhakkak Esfahani
Tongta Sae-Ong
Sascha Schäuble
Bastian Seelbinder
Lin Lin Xu

Publications

Kämmer P, McNamara S*, Wolf T, Conrad T, Allert S, Gerwien F, Hünniger K, Kurzai O, Guthke R, Hube B, Linde J, Brunke S (2020) Survival strategies of pathogenic Candida species in human blood show independent and specific adaptations. mBio 11(5), e02435-20.
Khaliq W, Großmann P, Neugebauer S, Kleyman A, Domizi R, Calcinaro S, Brealey D, Gräler M, Kiehntopf M, Schäuble S, Singer M, Panagiotou G**, Bauer M**(corresponding authors**) (2020) Lipid metabolic signatures deviate in sepsis survivors compared to non-survivors. Comput Struct Biotechnol J 18, 3678-3691.
Machata S, Müller MM, Lehmann R, Sieber P, Panagiotou G, Carvalho A, Cunha C, Lagrou K, Maertens J, Slevogt H, Jacobsen ID (2020) Proteome analysis of bronchoalveolar lavage fluids reveals host and fungal proteins highly expressed during invasive pulmonary aspergillosis in mice and humans. Virulence 11(1), 1337-1351.
Merk R, Heßelbach K, Osipova A, Popadić D, Schmidt-Heck W, Kim GJ, Günther S, Piñeres A G, Merfort I, Humar M (2020) Particulate matter (PM2.5) from biomass combustion induces an anti-oxidative response and cancer drug resistance in human bronchial epithelial BEAS-2B cells. Int J Environ Res Public Health 17(21), 8193.
Reimann L, Schwäble AN, Fricke AL, Mühlhäuser WWD, Leber Y, Lohanadan K, Puchinger MG, Schäuble S, Faessler E, Wiese H, Reichenbach C, Knapp B, Peikert CD, Drepper F, Hahn U, Kreutz C, van der Ven PFM, Radziwill G, Djinović-Carugo K, Fürst DO, Warscheid B (2020) Phosphoproteomics identifies dual-site phosphorylation in an extended basophilic motif regulating FILIP1-mediated degradation of filamin-C. Commun Biol 3(1), 253.
Seelbinder B, Chen J, Brunke S, Vazquez-Uribe R, Santhanam R, Meyer AC, de Oliveira Lino FS, Chan KF, Loos D, Imamovic L, Tsang CC, Lam RP, Sridhar S, Kang K, Hube B, Woo PCY, Sommer MOA, Panagiotou G (2020) Antibiotics create a shift from mutualism to competition in human gut communities with a longer-lasting impact on fungi than bacteria. Microbiome 8(1), 133.
Shopova IA, Belyaev I, Dasari P, Jahreis S, Stroe MC, Cseresnyés Z, Zimmermann AK, Medyukhina A, Svensson C-M, Krüger T, Szeifert V, Nietzsche S, Conrad T, Blango MG, Kniemeyer O, von Lilienfeld-Toal M, Zipfel PF, Ligeti E, Figge MT, Brakhage AA (2020) Human neutrophils produce antifungal extracellular vesicles against Aspergillus fumigatus. mBio 11(2), e00596-20.
Tomasovic A, Brand T, Schanbacher C, Kramer S, Hümmert MW, Godoy P, Schmidt-Heck W, Nordbeck P, Ludwig J, Homann S, Wiegering A, Shaykhutdinov T, Kratz C, Knüchel R, Müller-Hermelink HK, Rosenwald A, Frey N, Eichler J, Dobrev D, El-Armouche A, Hengstler JG, Müller OJ, Hinrichs K, Cuello F, Zernecke A, Lorenz K (2020) Interference with ERK-dimerization at the nucleocytosolic interface targets pathological ERK1/2 signaling without cardiotoxic side-effects. Nat Commun 11(1), 1733.
Barber AE*, Weber M, Kaerger K, Linde J, Gölz H, Duerschmied D, Markert A, Guthke R, Walther G, Kurzai O (2019) Comparative genomics of serial Candida glabrata isolates and the rapid acquisition of echinocandin resistance during therapy. Antimicrob Agents Chemother 63(2), e01628-18.
Fabian A, Stegner S, Miarka L, Zimmermann J, Lenk L, Rahn S, Buttlar J, Viol F, Knaack H, Esser D, Schäuble S, Großmann P, Marinos G, Häsler R, Mikulits W, Saur D, Kaleta C, Schäfer H, Sebens S (2019) Metastasis of pancreatic cancer: An uninflamed liver micromilieu controls cell growth and cancer stem cell properties by oxidative phosphorylation in pancreatic ductal epithelial cells. Cancer Lett 453, 95-106.