Our research is focused on the molecular mechanism of sepsis and inflammation and how they can be translated into the clinics.



German Version

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:


Immunophenotyping of sepsis patient clusters
We will investigate the immune status of sepsis patients to measure the activation state (hyperinflammation vs. immunosuppression) and cytokine response of diverse immune cells in clinical patient clusters. To this end, we will investigate cell type-specific signaling pathways in various patient clusters identified by machine learning by combining different analysis techniques, such as single-cell sequencing, mass spectrometry, and flow cytometry, to identify new potential therapeutic targets.

Detection of platelet aggregates in sepsis using POC flow microscopy Cellface
In cooperation with Prof. Hayden, we investigate platelet aggregates’ composition and clinical significance. For this purpose, we investigate the actuating value holographic POC flow microscopy Cellface and the composition and activation of platelet aggregates by imaging flow microscopy.

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.

In-vivo investigation of neuroinflammation in septic encephalopathy using EEG
In cooperation with AG Fenzl, our group is investigating in vivo the role and detectability of neuroinflammation in septic encephalopathy using EEG.


Team:

  • Dr. med. univ. Johannes Krell: Deals with machine learning to identify patient disease- and course-specific patient groups, their biological significance, and the role of platelet aggregates in sepsis.
  • Korbinian Schreyer: Investigates the effects of netrin-1 on the course of sepsis in vivo and in vitro
  • cand. med. Sabrina Burdorf: Investigates the cell-specific course of sepsis of patients in our intensive care unit using FACS and CellFace in cooperation with Prof. Oliver Haydn
  • cand. med. Jan Brauer: Investigates the cell-specific cytokine response and lipid mediator production and their influence on the course of the disease in intensive care Covid19 patients.
  • cand. med. Laura Ziegon: Investigates the role of the neuronal guidance protein Netrin-1 in sepsis in our intensive care unit patients.
  • cand. med. Severin Fuchs: Investigates the in-vitro immune response of sepsis patients and its therapeutic influenceability
  • cand. med. Julia Stettmer: Investigates the role of cell-specific netrin-1 in the in-vivo model of sepsis
  • cand. med. Thomas Schlenker: Investigates the immunological differences in the cell-specific immune response and the formation of thrombocyte aggregates in patients with ARDS
  • cand. med. Stephanie Schmidt: Investigates the formation of platelet aggregates and their immunological significance already in the early phase and during the course of sepsis.
  • cand. med. Nikita van Witzenburg: During her research semester at the University of Utrecht, Nikita visited our lab for six months and investigated the influence of netrin-1 on cell differentiation in-vitro


Methods:

  • Clinical observation study determining immunological cluster in sepsis patients using machine learning
  • 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
  • Raphael Reuten, Professor for Matritecture, Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität Freiburg
  • 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

Publications:

2023
Troseid M, Arribas JR, Assoumou L, Holten AR, Poissy J, Terzic V, Schlegel M et al.
Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial.
Crit Care. 2023;27(1):9.

2022
Blazer A, Qian Y, Schlegel M, Algasas H, Buyon JP, Cadwell K, et al.
APOL1 variant-expressing endothelial cells exhibit autophagic dysfunction and mitochondrial stress.
Front Genet. 2022;13

Wang X, Shi Q, Pradhan AK, Ziegon L, Schlegel M, Rammes G.
Beta-Site Amyloid Precursor Protein-Cleaving Enzyme Inhibition Partly Restores Sevoflurane-Induced Deficits on Synaptic Plasticity and Spine Loss.
Int J Mol Sci. 2022;23(12).

2021
Ziegon L, Schlegel M.
Netrin-1: A Modulator of Macrophage Driven Acute and Chronic Inflammation.
Int J Mol Sci. 2021;23(1).

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.

2020
Tikkinen KAO, Malekzadeh R, Schlegel M, Rutanen J, Glasziou P. COVID clinical trials: learning from exceptions in the research chaos. Nature medicine. 2020.

Koelwyn GJ, Newman AAC, Afonso MS, Solingen Cv, Corr EM, Brown EJ, Albers KB, Yamaguchi N, Narke D, Schlegel M, Sharma M, Shanley LC, Barrett TJ, Mezzano KRV, Fisher EA, Park DS, Newman JD, Quail DF, Nelson ER, Caan BJ, Jones LW and Moore KJ. Myocardial Infarction Accelerates Breast Cancer via Innate Immune Reprogramming. 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.

2019
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

2018
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.

früher
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


German Version