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Miguel and Chandini publish Report in Science! Congrats!

Miguel and Chandini publish Report in Science! Congrats!

Title: “Host DNases prevent vascular occlusion by neutrophil extracellular traps”

Weblink: http://science.sciencemag.org/content/358/6367/1202

Positions for PhD and Postdoctoral Fellows

Positions for PhD and Postdoctoral Fellows are available on a rolling basis to highly motivated candidates with the following qualifications:

• Master or diploma in biochemistry, cell biology, immunology, or a related field
• Strong academic record and knowledge in biochemistry, cell biology, and immunology
• Strong interest in inflammation, innate and adaptive immunity, and vascular biology
• Experience in basic science research and translational medicine
• Experience in murine disease models and FELASA certification is a plus
• Proficiency in English is required
• PhD in inflammation, immunity, or related field (Postdoc applicants only)
• 1+ first author publication in a top-tier journal (Postdoc applicants only)

Please submit your curriculum vitae, a statement of your research interests, and contact information of two academic references in electronic form to:

Tobias Fuchs, PhD
Principal Investigator
Laboratory of Molecular Inflammation
University Medical Center Hamburg-Eppendorf
Institute of Clinical Chemistry and Laboratory Medicine
Martinistraße 52, 20246 Hamburg, Germany
E-Mail: fuchs@inflammation.de
Web: www.inflammation.de

Dr. Boettcher and LMI publish article in Scientific Reports!

Dr. Boettcher and LMI publish article in Scientific Reports!

Title: “Therapeutic targeting of extracellular DNA improves the outcome of intestinal ischemic reperfusion injury in neonatal rats”

Weblink: https://www.nature.com/articles/s41598-017-15807-6

Abstract: Thrombosis and inflammation cooperate in the development of intestinal infarction. Recent studies suggest that extracellular DNA released by damaged cells or neutrophils in form of extracellular traps (NETs) contributes to organ damage in experimental models of ischemia-reperfusion injury. Here we compared the therapeutic effects of targeting fibrin or extracellular DNA in intestinal infarction after midgut volvulus in rats. Following iatrogenic midgut volvulus induction for 3 hours, we treated animals with a combination of tissue plasminogen activator (tPA) and low molecular weight heparin (LMWH) to target fibrin or with DNase1 to degrade extracellular DNA. The therapeutic effects of tPA/LMWH and DNase1 were analyzed after 7 days. We observed that both therapeutic interventions ameliorated tissue injury, apoptosis, and oxidative stress in the intestine. DNase1, but not tPA/LMWH, reduced intestinal neutrophil infiltration and histone-myeloperoxidase-complexes, a surrogate marker of NETs, in circulation. Importantly, tPA/LMWH, but not DNase1, interfered with hemostasis as evidenced by a prolonged tail bleeding time. In conclusion, our data suggest that the therapeutic targeting of fibrin and extracellular DNA improves the outcome of midgut volvulus in rats. DNase1 therapy reduces the inflammatory response including NETs without increasing the risk of bleeding. Thus, targeting of extracellular DNA may provide a safe therapy for patients with intestinal infarction in future.

Rachita publishes article in Frontiers of Immunology. Congrats!

Rachita publishes article in Frontiers of Immunology. Congrats!

Title: “Neutrophil Extracellular Traps Contain Selected Antigens of Anti-Neutrophil Cytoplasmic Antibodies.”

Weblink: https://www.frontiersin.org/articles/10.3389/fimmu.2017.00439/full

Abstract: Neutrophil extracellular traps (NETs) are chromatin filaments decorated with enzymes from neutrophil cytoplasmic granules. Anti-neutrophil cytoplasmic antibodies (ANCAs) bind to enzymes from neutrophil cytoplasmic granules and are biomarkers for the diagnosis of systemic vasculitides. ANCA diagnostics are based on indirect immunofluorescence (IIF) of ethanol-fixed neutrophils. IIF shows a cytoplasmic staining pattern (C-ANCA) due to autoantibodies against proteinase 3 (PR3) or a perinuclear staining pattern (P-ANCA) due to autoantibodies against myeloperoxidase (MPO). The distinct ANCA-staining patterns are an artifact of ethanol fixation. Here, we tested NETs as a substrate for the detection of ANCAs in human sera. We observed that P-ANCAs specifically stained NETs, while C-ANCAs targeted the cell bodies of netting neutrophils. The distinct ANCA-staining patterns were caused by the presence of MPO, but not PR3, in NETs. Using NETs as a substrate for IIF, we characterized ANCAs in sera of patients with ANCA-associated vasculitis (AAV). Furthermore, we inhibited serine proteases by diisopropylfluorophosphate to prevent chromatin unfolding and the release of NETs and thus generated neutrophils with MPO-positive nuclei and PR3-positive cytoplasm, which resembled the appearance of ethanol-fixed neutrophils. In conclusion, our data suggest that NETs are selectively loaded with antigens recognized by P-ANCAs, and netting neutrophils provide a physiological substrate for ANCA detection in patients with AAV.

Talk at ISTH 2017

Tobias Fuchs gives a talk entitled “Contribution of NETs to Thrombosis” at ISTH 2017 in Berlin.

Date: July 11th / 14:45 – 16:15
Link: http://www.isth2017.org/

Myelène Divivier joins the lab

Welcome!

Review in STH

Miguel publishes a review about “Circulating extracellular DNA – cause or consequence of thrombosis?” in Seminars in Thrombosis and Hemostasis (doi: 10.1055/s-0036-1597284).

Jingang Huang joins the lab

Welcome!

Open Positions for PhD and Postdoctoral Fellows

 

The Institute of Clinical Chemistry and Laboratory Medicine at the University Medical Center Hamburg-Eppendorf offers PhD and Postdoctoral Fellowships in Molecular Inflammation.

Our newly established laboratory studies the role of Neutrophil Extracellular Traps (NETs) in acute inflammation. NETs are lattices of extracellular DNA filaments, which are liberated from activated neutrophil granulocytes during infection and sterile inflammation. NETs are toxic to microbes as well as hosts cells and have the capacity to activate adaptive immune responses. However, the molecular mechanisms how NETs regulate the progression or outcome of inflammation are poorly understood. Our research is focused on, but not restricted to, inflammatory diseases of the cardiovascular system, hepatobiliary tract, and kidneys. The project is embedded in the research initiative “I3 – Inflammation, Infection, Immunity” of the University Medical Center Hamburg-Eppendorf.

To characterize the role of NETs in inflammation, the successful candidates will be using primary cell culture and murine disease models in combination with state-of-the-art molecular biology methods, intravital imaging, and high-throughput technology.

For further reading visit our website: http://www.inflammation.de

We are looking for outstanding and highly motivated candidates with the following qualifications:
• Master or diploma in biochemistry, cell biology, immunology, or a related field
• Strong academic record and knowledge in biochemistry, cell biology, and immunology
• Strong interest in inflammation, innate and adaptive immunity, and vascular biology
• Experience in basic science research and translational medicine
• Experience in murine disease models and FELASA certification is a plus
• Proficiency in English is required
• PhD in inflammation, immunity, or related field (Postdoc applicants only)
• 1+ first author publication in a top-tier journal (Postdoc applicants only)

Research will be conducted in the recently established Laboratory of Molecular Inflammation at the Institute for Clinical Chemistry and Laboratory Medicine. The laboratory space is located in a new research building of the University Medical Center Hamburg-Eppendorf, which provides an outstanding infrastructure with a wide range of core facilities.

PhD students will enroll in the doctoral program at the Medical Faculty of Hamburg University, which offers an excellent educational framework for students with basic science and medical background.

For further information visit: http://www.phd-medical-faculty-hamburg.de

Please submit your curriculum vitae, a statement of your research interests, and contact information of two academic references in electronic form to:

Tobias Fuchs, PhD
Principal Investigator
Laboratory of Molecular Inflammation
University Medical Center Hamburg-Eppendorf
Institute of Clinical Chemistry and Laboratory Medicine
Martinistraße 52, 20246 Hamburg, Germany
E-Mail: fuchs@inflammation.de
Web: www.inflammation.de

The positions are extramurally funded for up to 4 years and will be open until filled.

The University Medical Center Hamburg-Eppendorf supports equal employment opportunities. Preference will be given to female applicants or severely handicapped persons with equal qualifications.

LMI Receives Young Investigator Award

Tobias Fuchs receives a Eberhard F. Mammen Young Investigator Award 2015 >>