Our research is focused on the molecular mechanism of sepsis and inflammation and how they can be translated into the clinics.
We focus on the adaptive and innate immune response and specifically on its progressive change during inflammation. To advance our basic research to the clinics, we are performing clinical trials as well as various in-vivo and in vitro models.
Studies and Trials:
Prof. Schneider and Dr. Schlegel will chair as national clinical coordinators the enrollment and coordination of the SolidAct trial in Germany. As part of the EU-Response program to the Covid19 pandemic the EU initiated the pan-european Solid Act trial. Firstly, the project focuses on test potentialing treatments for COVID-19. Secondly, the EU-RESPONSE aims to design and run a new adaptive European platform trial for emerging infectious diseases, called EU-SolidAct, thus improving Europe’s responsiveness to pandemic crises.
SolidAct Trial Germany
The ASSESS-Sepsis trial (Analysis of the Immune Status In SepSiSpatients) will assess the immune state (hyperinflammation vs immunosuppression) of sepsis patients and their cell-specific cytokine profile. Combining single cell sequencing with HPLC-MS/MS and flowcytometry will help us to identify cell-specific pathways and molecular targets within various patient clusters.
In vivo and in vitro models on the role of stress and guidance molecules in sepsis
Using several tracing and knock-out models allows us to study in-vivo and in-vitro, how genetic aberrations, stress or various moleculs impact the genetic imprinting and the resulting cellular immune response. Moreover, we are studying in another model the neuroinflammatory change during septic encephalopathy.
- Dr. med. univ. Johannes Krell: Johannes studies machine learning and data integration to identify patient specific cluster in sepsis and the disease progression.
- cand. med. Sabrina Burdorf: Sabrina investigates specific Sepsis progression of ICU patients might be assessed and predicted by flow cytometry and highthrough put holographic microscopy „CellFace“ (in co-operation with Prof. Oliver Hayden).
- cand. med. Jan Brauer: Jan explores how cell specific lipid mediators and cytokines impact the disease progression of SarsCoV2 patients on our ICU.
- cand. med. Laura Ziegon: Laura studies the impact of the neuronal guidance protein Netrin-1 on ICU patients and conditional, cellspecific knockout mice.
- Clinical observation study determining immunological cluster in sepsis patients
- scRNA sequencing, FACS analysis und Cell Sorting
- Basic molecular biology techniques: e.g. in-vitro und ex-vivo cell culture, qRT-PCR, WesternBlot, ELISA, CBA-based cytokine arrays
- Acute and chronic inflammatory in-vivo models
Internal and external collaboration partners:
- Kathryn Moore, Director of the NYU Cardiovascular Research Center, New York
- Clarissa Prazeres da Costa, Director Munich Center of Global Health und Institute for Microbiology, TUM
- Jason Hellman, Assistant Professor, Diabetes and Obesity Center, University of Louisville, KY, US
- Oliver Hayden, Chair of Biomedical Electronics, Department of Electrical and Computer Engineering, TranslaTUM
- Thomas Fenzl, Klinik für Anästhesie, Klinikum rechts der Isar, TUM
- Gerhard Rammes, Klinik für Anästhesie, Klinikum rechts der Isar, TUM
Schlegel M, Sharma M, Brown EJ, Newman AAC, Cyr Y, Afonso MS, Corr EM, Koelwyn GJ, van Solingen C, Guzman J, Farhat R, Nikain CA, Shanley LC, Peled D, Schmidt AM, Fisher EA, Moore KJ. Silencing Myeloid Netrin-1 Induces Inflammation Resolution and Plaque Regression. Circ Res 129(5): 530-546. 2021.
Afonso MS, Sharma M, Schlegel M, van Solingen C, Koelwyn GJ, Shanley LC, Beckett L, Peled D, Rahman K, Giannarelli C, Li H, Brown EJ, Khodadadi-Jamayran A, Fisher EA, Moore KJ. miR-33 Silencing Reprograms the Immune Cell Landscape in Atherosclerotic Plaques Circulation Research. 2021.
Afonso MS, Verma N, van Solingen C, Cyr Y, Sharma M, Perie L, Corr EM, Schlegel M, Shanley LC, Peled D, Yoo JY, Schmidt AM, Mueller E, Moore KJ. MicroRNA-33 Inhibits Adaptive Thermogenesis and Adipose Tissue Beiging. ATVB. 2021.
Tikkinen KAO, Malekzadeh R, Schlegel M, Rutanen J, Glasziou P. COVID clinical trials: learning from exceptions in the research chaos. Nature medicine. 2020.
Schlegel M and Moore KJ. A heritable netrin-1 mutation increases atherogenic immune responses. Atherosclerosis. 2020.
Sharma M, Schlegel M, Afonso MS, Brown EJ, Rahman K, Weinstock A, Sansbury B, Corr EM, van Solingen C, Koelwyn G, Shanley LC, Beckett L, Peled D, Lafaille JJ, Spite M, Loke P, Fisher EA and Moore KJ. Regulatory T Cells License Macrophage Pro-Resolving Functions During Atherosclerosis Regression. Circulation research. 2020.
Schlegel M, Koelwyn GJ, Moore KJ. Connecting Transcriptional and Functional Macrophage Heterogeneity in Atherosclerosis. Circulation research. 2019;125(12):1052-4.
Barrett TJ, Schlegel M, Zhou F, Gorenchtein M, Bolstorff J, Moore KJ, et al. Platelet regulation of myeloid suppressor of cytokine signaling 3 accelerates atherosclerosis. Sci Transl Med. 2019;11(517).
Sharma M, Schlegel M, Brown EJ, Sansbury BE, Weinstock A, Afonso MS, et al. Netrin-1 Alters Adipose Tissue Macrophage Fate and Function in Obesity. Immunometabolism. 2019;1(2).
Korner A, Schlegel M, Kaussen T, Gudernatsch V, Hansmann G, Schumacher T, et al. Sympathetic nervous system controls resolution of inflammation via regulation of repulsive guidance molecule A. Nat Commun. 2019.
Schlegel M, Korner A, Kaussen T, Knausberg U, Gerber C, Hansmann G, et al. Inhibition of neogenin fosters resolution of inflammation and tissue regeneration. JCI. 2018.
Korner A, Schlegel M, Theurer J, Frohnmeyer H, Adolph M, Heijink M, Giera M, Rosenberger P, Mirakaj V. Resolution of inflammation and sepsis survival are improved by dietary Omega-3 fatty acids. Cell Death Differ. 2018.
König K, Granja T, Eckle VS, Mirakaj V, Köhler D, Schlegel M, Rosenberger P. Inhibition of Plexin C1 Protects Against Hepatic Ischemia-Reperfusion Injury. Crit Care Med. 2016.
Schlegel M, Kohler D, Korner A, Granja T, Straub A, Giera M, Mirakaj V. The neuroimmune guidance cue netrin-1 controls resolution programs and promotes liver regeneration. Hepatology. 2015.
Schlegel M, Granja T, Kaiser S, Korner A, Henes J, Konig, Straub A, Rosenberger P, Mirakaj V. Inhibition of Neogenin Dampens Hepatic Ischemia-Reperfusion Injury.Crit Care Med. 2014.
Schlegel PM, Steiert I, Kötter I, Müller CA. B cells contribute to heterogeneity of IL-17 producing cells in rheumatoid arthritis and healthy controls. PLoS One. 2013.