Our profile

What we do

The Sektion Experimentelle Anaesthesiologie of Prof. Dr. E. Marion Schneider pursues monocytes and immature dendritic cells in septic as well as in solid tumor patients which can be enriched by cell culture techniques from peripheral blood, bone marrow and cerebrospinal fluid. Such immature dendritic cells are resistant to maturation signals and manifest impressive hemophagocytic properties. Function and phenotype support the concept immunologic anergy in sepsis and malignancies.

Image 1: Hypothesis to explain the survival of iDC in states of inflammation and NK deficiencies

Since 2007, Eos-FP, a novel fluorescent dye, isolated from a marine organism by Joerg Wiedenmann (Univ. Souphampton, U.K., former Ulm University), is applied to study phagocytosis using Eos-FP-transfected bacteria. Early after ingestion, bacteria emit red and green fluorescent light. After fusion of the phasome with acidic lysosomes, the red fluorescence is lost and partially degraded bacteria emit only green fluorescent light.

Image 2: Degraded and non-degraded Bacteria, Schreiner et al. 2011

We hold an immunological cell, DNA and data bank on hemophagocytic lymphohistiocytosis (HLH) and hyperinflammatory diseases many of which are monogenetic, or manifest HLH during immune dysfunction and states of virus-re-activation. The biological material: mononuclear cells, bone marrow, cell lines, fibroblasts and endothelial cells, as well as sera and DNA are derived from > 2000 individual patients' samples and 200 - 300 families. Flow cytometric analyses, ex-vivo stimulation protocols, plasma cytokines and cellular cytolysis assays have been determined to be correlated with genetic testings of functional polymorphisms encoded in the gene for a purinergic ion channel receptor, P2RX7, the Toll-like-receptors 2 and 4, Perforin, and enzymes related to oxidative stress. All SNPs were determined by pyrosequencing technologies. A recently detected SNP haplotype appears to be relevant for the manifestation of severe sepsis. Phenotypically, P2RX7 is highly expressed in immature dendritic cells of patients. Upon activation by ATP in vivo, such as by trauma, P2RX7 generates a calcium signal and thus amplifies inflammatory signaling pathways by the secretion of IL-1β.

Image 3: P2RX7 stimulation by ATP in wild type dendritic cells.

Image 4: ATP stimulated IL-1ß secretion by LPS-primed sepsis-APC, Schneider et al. 2011

Another field of interest concentrates on ultrastructural studies of patients’ derived immature dendritic cells and their unique characteristic in autophagy. ATP stimulates the expression of  LC3, a component of the autophagosome, as determined by flow cytometry.

Image 5: Upregulation of LC3 expression by treatment with 1mM ATP for 3 h. Negative control (black line histogram); LC3-positive cells (red line histogram). Schneider et al. 2011

Schneider, E.M., Lorenz, M.R., Walther, P. Autophagy  as a hallmark of hemophagocytic diseases. In „Autophagy in Health and Diseases.“ (N. V. Gorbunov (ed.) NOVA Publishers N.Y. 2011.

Image 6: Tomogram of a representative and autophagic vesicle-rich hemophagocyte.

We provide knowledge of immune interaction pathways leading to immune incompetence in major inflammatory diseases. With our team, we developed a mitochondrial SNP typing array for mitochondrial mutations within a European Research Project in FP5.  For patients with hemophagocytic diseases and inflammsome-realted macrophage activation syndromes, we provide short and long-term assays for Natural Killer Cell Functional Analysis. Our group participated in the STREP “GenOSept” of FP6 to establish a SNP platform for the identification of inflammatory genes related to the manifestation of severe sepsis in adult patients suffering from bacterial infections or non-infectious complications such as pancreatitis. In FP7, Marion Schneider and her team were responsible for the development of a single cell based multiplex PCR to detect Epstein Barr Virus (EBV) in immature dendritic cells, called QuAGSiC (quantitative analysis  of Genes in single cells). In collaboration with Alberto Pasquarelli (Institut für Elektronische Bauelemente und Schaltungen, Univ. Ulm), a diamond based chip has been set up to determine potentiometric as well as amperometric measurements of P2RX7 stimulated cells).

Image 7: ATP-induced P2RX7 activation on diamond chip . Ca++ translocation and subsequent generation of amperometric signals detected.

Recently, our group concentrated on the Calcium-dependent formation of neutrophil derived extracellular traps (NETs). Results suggest that increased NETosis by neutrophils is an excellent indicator to follow clinical changes in patients with sepsis. Infectious complications as well as traumatic injury lead to massive NETformation and correlate with biomarkers such as LBP (liposolysaccharide binding protein), IL-1β, IL-6, IL-8, or TNF-α, leukocyte increase, and CRP.

Image 8: NETosis of neutrophilic granulocytes and demonstration of neutrophil derived primary granules (arrows).

Contact

Office Tel.:

+49 - 731 - 50060080/81

Office Fax:

+49 - 731 - 50060082

Laboratory:

+49 - 731 - 50060083/84/85

Our team

  • Profilbild von Prof. Dr. rer. nat. E. Schneider

    Prof. Dr. rer. nat. E. Schneider

    Sektionsleiterin Experimentelle Anästhesiologie | Head of the Division Experimental Anesthesiology

    Schwerpunkte

    Experimentelle Anästhesiologie | Experimental Anesthesiology

Marion Schneider, Prof., Dr. rer. nat., focuses on the development of biomarker protocols for immune-based diagnostics in inflammatory diseases. She holds a data base of >20,000 patients with immune phenotypes and cytokine expression patterns, and functional SNPs. Biological materials such as PBMC, plasma, DNA, RNA are archived. Teaching concentrates on practical courses in Immunology, SNP sequencing and ex-vivo modeling of disease states for students in Molecular and Human Medicine.

  • Profilbild von Ning Dan

    Ning Dan

Ning Dan, M. Sc. MD, studies patients with pain syndromes and metabolic dysfunction including diabetes mellitus II, and sepsis for SNP polymorphisms and macrophage activation.

Manfred Weiss, Prof. Dr. med. MA, cooperates on patients with leukopenia and the beneficial effects by G-CSF.

Karl Föhr, PD, Dr. rer. nat., runs an electrophysiological lab, performing patch-clamp recordings at ligand- and voltage-gated ion channels using primary cells (e.g. neurons) or heterologous expression systems (HEK-293).  

  • Profilbild von Li Chen

    Li Chen

Li, Chen, M. Sc., PhD student (biol. hum.), studies immune macrophage subclassification, functional phagocytosis and entosis assays, by video microscopy, PCR of miRNA species related to chronic inflammation.

  • Profilbild von Christian Scheiber

    Christian Scheiber

Scheiber, Christian, M. Sc., PhD student (Mol Med.), works on isolated microparticles and exosomes from CSF of psychiatric patients and patients with subarachnoidal bleeding. His virus diagnostics are based on miRNA signatures.

Stefan Baeder, (engineer), is responsible for confocal scanning microscopy and set up of flow assay for microscopical devices including video microscopy and migration of inflammatory cells.

  • Profilbild von Hans Klein

    Hans Klein

Hans Klein, is our guest scientist as part of the EU project MOOD STRATIFICATION.

  • Profilbild von Marla Teufel

    Marla Teufel

Marla Teufel, does your federal voluntary service in our team.

Diseases

Hemophagocytic Lymphohistiocytosis

References:

Lin, M, Park, S,  Hayden, A, Giustini, D, Trinkaus, M, Pudek, M, Mattman, A, Schneider, M, and Chen, LYC. Clinical utility of soluble interleukin-2 receptor in hemophagocytic syndromes: a systematic scoping review. Annals of Hematology 96 (2017) 1241-1251

Janka, G, Schneider, EM. Hämophagozytische Lymphohistiozytosen. In: Gadner H, Gaedicke G, Niemeyer C, Ritter J (eds). Pädiatrische Hämatologie und Onkologie. Springer Medizin Verlag Heidelbert; 2006. ISBN 10-3-540-03702-0

Titze, U., G. Janka, E.M. Schneider, F. Prall, D. Haffner, and C.F. Classen. 2009. Hemophagocytic lymphohistiocytosis and Kawasaki disease: combined manifestation and differential diagnosis. Pediatr Blood Cancer. 2009; 53:493-5.

Woehrle T, Du W, Goetz A, Hsu H, Joos T, Weiss M, Bauer U, Brueckner U, Schneider EM. Pathogen specific cytokine release reveals an effect of TLR2 Arg753Gln during Candida sepsis in humans. Cytokine 2007,

Edner J, Rudd E, Zheng C, Dahlander A, Eksborg S, Schneider EM, Edner A, Henter JI. Severe bacteria-associated hemophagocytic lymphohistiocytosis in an extremely premature infant. Acta Paediatr 2007, 96:1703-1706.

Horne A, Zheng C, Lorenz I, Lofstedt M, Montgomery SM, Janka G, Henter JI, Marion Schneider E. Subtyping of natural killer cell cytotoxicity deficiencies in haemophagocytic lymphohistocytosis provides therapeutic guidance. Br J Haematol 2005, 129:658-666.

Janka GE, Schneider EM. Modern management of children with haemophagocytic lymphohistiocytosis. Brit. J. Hematol 2004, 124: 4-14.

Schneider, EM. Bullfight without killer weapons: interferon rules pathology in HLH. Blood 2004, 104(3): 600 – 601.

zur Stadt U, Kabisch H, Janka G, Schneider EM. Rapid LightCycler assay for screening of the codon 374 Trp->stop mutation in patients and families with hemophagocytic lymphohistiocytosis (FHLH). Med Pediatr Oncol 2003; 41(1): 26-9

Schneider EM, Lorenz I, Muller-Rosenberger M, Steinbach G, Kron M, Janka-Schaub GE. Hemophagocytic lymphohistiocytosis is associated with deficiencies of cellular cytolysis but normal expression of transcripts relevant to killer-cell-induced apoptosis. Blood 2002;100(8):2891-8.

zur Stadt U, Pruggmayer M, Jung H, Henter JI, Schneider EM, Kabisch H,Janka G. Prenatal diagnosis of perforin gene mutations in familial hemophagocytic lymphohistiocytosis (FHLH). Prenat Diagn 2002;22(1):80-1

Clementi, R. zur Stadt, U., Savoldi, G., Varoitto, S., Conter, V., De Fusco, C. Notarangelo, U.L., Schneider, E. M., Klersy, C., Janka, G., Danesino, C., Arico, M. Six novel mutations in the PRF1 gene in children with haemophagocytic lymphohistiocytosis. J Med Genet 2001; 38(9):643-6

Durken M, Horstmann M, Bieling P, Erttmann R, Kabisch H, Loliger C, Schneider EM, Hellwege HH, Kruger W, Kroger N, Zander AR, Janka GE. Improved outcome in haemophagocytic lymphohistiocytosis after bone marrow transplantation from related and unrelated donors: a single-centre experience of 12 patients. Br.J.Haematol. 1999;106(4):1052-1058.

Dufourcq-Lagelouse R, Jabado N, Le Deist F, Stephan JL, Souillet G, Bruin M, Vilmer E, Schneider M, Janka G, Fischer A,de Saint BG. Linkage of familial hemophagocytic lymphohistiocytosis to 10q21-22 and evidence for heterogeneity. Am.J.Hum.Genet. 1999;64(1):172-179.

Janka G, Imashuku S, Elinder G, Schneider EM, Henter JI. Infection-and malignancy-associated Hemophagocytic Syndromes. Hematol.Oncol.Clin.North Am. 1998;12(2):435-444.

Durken M, Schneider EM, Blutters-Sawatzki R, Stollmann-Gibbels B, Nessler G, Bretz R, Korholz D, Probst EN, Holsten-Griffin H, Harps E, Zander AR,Janka GE. [Treatment of hemophagocytic lymphohistiocytosis, HLH, with bone marrow transplantation]. Klin.Padiatr. 1998;210(4):180-184.

Kusenbach G, Rubben A, Schneider EM, Barker M, Bussing A, Lassay L, Skopnik H,Heiman G. Herpes virus (KSHV) associated Kaposi sarcoma in a 3-year-old child with non-HIV-induced immunodeficiency. Eur.J.Pediatr. 1997;156(6):440-443.

Macrophage Activation Syndromes

References:

Walther P, Bauer A, Wenske N, Catanese A, Garrido D, Schneider EM. (2018) STEM tomography of high-pressure frozen and freeze-substituted cells: a comparison of image stacks obtained at 200 kV or 300 kV. Histochem Cell Biol. 2018 Sep 18. doi: 10.1007/s00418-018-1727-0. [Epub ahead of print]

Schneider EM, Flacke, S, Liu, F, Lorenz, MR, Schilling, P, Nass, ME., Foehr, KJ, Huber-Lang, Markus, Weiss, Manfred E. Autophagy and ATP-induced anti-apoptosis in antigen presenting cells (APC) follows the cytokine storm in patients after major trauma Journal of Cell Communication and Signaling. 2011, 5:145-156.

Waqas, SF, Hassnain, Hoang, AC, Lin, Y-T, Ampem, G., Azegrouz, H, Balogh, L, Thuróczy, J, Chen, J-C, Gerling, IC, Nam, S, Lim, J-S, Martínez-Ibañez, J, Real, J, Paschke, S, Quillet, R, Ayachi, S, Simonin, F, Schneider, EM, Brinkman, JA, Lamming, DW, Seroogy, CM, Röszer, T. Neuropeptide-FF increases M2 activation and self-renewal of adipose tissue macrophages. J Clin Investigation 2017 in press.

Pain Syndromes

Under Construction

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Trauma, Sepsis, Septic Shock

References:

Denzinger, M, Staendker, L, Ehlers, K, Schneider, JM, Schulz, T, Hein, T, Wiese, S,  Roecker, A, Gross, R, Muench, J,  Bracht, H, Barth, E, Weiss, M, Georgieff, M,  Schneider, EM. Bioassay for Endothelial Damage Mediators Retrieved by Hemoadsorption, Sci Rep. Sci Rep 9, 14522 (2019) doi:10.1038/s41598-019-50517-1

Geistlinger J, Du, W., Groll, J, Liu, F, Hoegel, J, Foehr, KJ, Pasquarelli, A, Schneider, EM. P2RX7 genotype association in severe sepsis identified by a novel Multi-Individual Array for rapid screening and replication of risk SNPs. Clin Chim Acta. 2011. DOI 10.1016/j.caa.2011.05.023.

Kriebel F, Wittemann S, Hsu HY, Joos T, Weiss M, Schneider EM. Caspase-3 activation, Bcl-2 contents, and soluble FAS-ligand are not related to the inflammatory marker profile in patients with sepsis and septic shock. Ann N Y Acad Sci 2006, 1090:168-176

Major Depression

References:

Mack, A, Pfeiffer, C, Schneider, EM, Bechter, K. Schizophrenia or Atypical Lupus Erythematosus with Predominant Psychiatric Manifestations over 25 Years: Case Analysis and Review. Front Psychiatry. 2017 Jul 27;8:131. doi: 10.3389/fpsyt.2017.00131. eCollection 2017.

Maxeiner HG, Marion Schneider E, Kurfiss ST, Brettschneider J, Tumani H, Bechter K. Cerebrospinal fluid and serum cytokine profiling to detect immune control of infectious and inflammatory neurological and psychiatric diseases. Cytokine 2014. 69:62-7.

Malignancies

References:

Sander, P, Walther, P, Moepps, B, Hinz, M, Mostafa, H, Schaefer, P, Pala, A, Wirtz, CR, Georgieff, M, and Schneider, EM. 2019. Mitophagy-Related Cell Death Mediated by Vacquinol-1 and TRPM7 Blockade in Glioblastoma IV. In: OMERHODZIC, I. & ARNAUTOVIĆ, K. (eds.) Glioma - Contemporary Diagnostics and Therapeutic Approaches. IntechOpen, 81-93.

Schneider, EM, Zielberg, D, Aigner, KR, Mostafa, H, Schneider, JM, Paschke, S. Systemic inflammation and immune suppression biomarkers in patients with solid tumors undergoing regional chemotherapy. Deutsche Zeitschrift für Onkologie Deutsche Zeitschrift für Onkologie 2017; 49: 8–14; DOI http://dx.doi.org/10.1055/s-0043-104756

Sander, S, Mostafa, H, Soboh, A, Schneider JM, Pala, A, Baron, A-K, Moepps, B, Wirtz, CR, Georgieff, M, Schneider, EM. Vacquinol-1 inducible cell death in glioblastoma multiforme is counter regulated by TRPM7 activity induced by exogenous ATP. ONCOTARGET, 2017.

Mostafa, H, Pala, A., Hoegel, J, Hlavac, M, Dietrich, E, Westhoff, AM, Nonnenmacher, L, Burster, T, Georgieff, M, Wirtz, CR, Schneider, EM. Immune phenotypes predict survival in patients with glioblastoma multiforme. J Hematol Oncol. 2016; Sep 1;9(1):77. doi: 10.1186/s13045-016-0272-3.

Persistent Treatment Resistant Lyme Borreliosis (pLB)

References:

Hein, T, Sander, P, Giryes, A., Reinhardt, J-O, Schneider, EM. Cytokine expression patterns and single nucleotide polymorphisms (SNPs) in patients with chronic borreliosis. Antibiotics 8:107 doi: 10.3390/antibiotics8030107

Diagnostic parameters and procedures

Shipping Material to our Laboratory

If you wish to send us material to perform diagnostics, please use the request sheet below.

Request Sheet (English)

Request Sheet (German)

Biomarkers

Cytokine concentrations in Plasma / CSF / Ascites indicate state of disease.
Surface marker phenotypes (FACS analysis) on white cells assist diagnostic accuracy.
In HLH (Hemophagocytic Lymphohistiocytosis) and MAS (Macrophage activation syndrome), NK (Natural Killer) cell function is impaired or NK-effector cells are significantly diminished.

Plasma biomarkers for inflammatory diseases

Results sheet of a healthy donor (example)

Immune Phenotypes

Phenotype analysis for inflammatory diseases

Example of a healthy donor (flow cytometry)

Whole Blood Stimulation for inflammatory and infectious diseases

Procedure

Research Application

Patients / Clinical Study Application

Examples of a clinical study

Examples of results obtained by TLR stimulation using TruCultures. IL-1ß release by healthy donors differs from patients with trauma or sepsis. Results have been presented at the TSIS 2010 meeting1.

1 Bindja J., Weiss M.E., Schmolz M., Stein G.M., Mapes J., Schneiderhan-Marra N., Joos J.O., Schneider E.M. Synthetic ligands against TLR2-9 in TruCultureTM - whole blood assays distinguish clinical stages of SIRS (trauma) and sepsis. Medimont Press, Proceedings Trauma, Shock, Inflammation and Sepsis, (2010) 55-63.

Whole blood phagocytosis assay

Using Eos-FP transfected E. coli, we provide an in-vitro phagocytosis assay to quantify the phagocytic activities of granulocytes and monocytes in whole blood and simulatenously monitor the phagosome-lysosome fusion process as described, previously (Schreiner et al. 2011); for more information see also (Dreschers et al. 2013 and Wiedenmann et al. 2004).

Literature:

Schreiner L, Huber-Lang, M, Weiss, ME, Hohmann, H, Schmolz, M., Schneider, EM. Phagocytosis and digestion of pH-sensitive fluorescent dye (Eos-FP) transfected E. coli in whole blood assays from patients with severe sepsis and septic shock. Journal of Cell Communication and Signaling. 2011, 5:139-144.

Dreschers, S., et al. Infection-induced bystander-apoptosis of monocytes is TNF-alpha-mediated. PLoS One 8, e53589.

Wiedenmann, J., et al. EosFP, a fluorescent marker protein with UV-inducible green-to-red fluorescence conversion. Proc Natl Acad Sci U S A 101, 15905-15910 (2004).

Research

... focuses on the development of biomarker protocols for immune-based diagnostics in inflammatory diseases. She holds a data base of >20,000 patients with immune phenotypes and cytokine expression patterns, and functional SNPs. Biological materials such as PBMC, plasma, DNA, RNA are archived. Teaching concentrates on practical courses in Immunology, SNP sequencing and ex-vivo modeling of disease states for students in Molecular and Human Medicine.

MOODSTRATIFICATION

Since 2018, we are working on the MOODSTRATIFICATION EU project, representing one of 12 international partners.

https://moodstratification.eu/

The major aim of MOODSTRATIFICATION is to identify as well as to stratify immune signatures in patients with chronic psychiatric diseases. We concentrate on microRNA (miRNA) profiling as a new signature for psychosis.

As part of a clinical study conducted among members of the MOODSTRATIFICATION consortium (Horizon 2020, https://www.horizont2020.de/) we enrich extracellular vesicles (EVs) from cerebrospinal fluid (CSF) for miRNA isolation. Moreover, EVs are characterized by ZetaView® and flow cytometry.

Immune phenotypes are determined from peripheral blood in analogy to tumor- and sepsis-associated profiles.

Extracellular vesicles (EVs)

Upon stimulation with triggers such as ATP, macrophages release EVs (Fig. 1) which may fuse with specific target tissues, representing a communication axis between the peripheral and central (brain) immune system. Analyzing the content of released EVs, one can derive an outlook at the current individual immune state. After collecting EVs by ultracentrifugation, we analyze their content with main focus on microRNAs (miRNAs) as a new class of biomarkers.

MicroRNA profiling

Preliminary results led us to concentrate on hsa-miR-146a (guiding Myd88-TRAF6-IRAK-4 stimulation) and hsa-miR-21 related to inflammation as well hypoxia-induced pathways.

An extended miRNA panel includes hsa-miR-155, hsv1-miR-H2 and hsv1-miR-H27 aiming at the selective involvement of HSV-1 in psychiatric diseases.

Results will be compared with CSF from patients with subarachnoidal bleeding (study ID: 021-07122010).

Figure 2 shows an example of EVs isolated from CSF and Figure 3 shows results of our miRNA profiling results.

Collaborations:

  • Prof. Dr. med. em. Karl Bechter (Klinik für Psychiatrie und Psychotherapie II (Günzburg), Universität Ulm) MOODSTRATIFICATION
  • Prof. Dr. med. Thomas Becker (Klinik für Psychiatrie und Psychotherapie II (Günzburg), Universität Ulm) MOODSTRATIFICATION
  • Paulo J. G. Kling Lourenço (Klinik für Psychiatrie und Psychotherapie II (Günzburg), Universität Ulm) MOODSTRATIFICATION
  • Dr. H. C. Klein (Faculty of Medical Sciences, Academic Centre of Psychiatry, Universiteit Groningen, The Netherlands) Virus reactivation and replication in psychiatric patients; HSV-1-derived miRNA profiling
  • Dr. Alexander Karabatsiakis (Klinische und Biologische Psychologie, Institut für Psychologie, Universität Innsbruck A-6020 Innsbruck) Mitochondrial respiratory assays
  • Prof. Dr. med. Thomas Kapapa (Klinik für Neurochirurgie, Universitätsklinikum Ulm)

Hemophagocytosis by Antigen-Presenting Cells

Hemophagocytic Cells in HLH

The electron micrograph shows hemophagocytic cells during (A) and after (B) ingesting streptavidin-coated iron beads. Histiocytic progenitors were isolated from the lymphocyte fraction of the peripheral blood of a patient with acute HLH following Ficoll separation. Iron-containing beads of precisely 5 μm in diameter are rapidly phagocytosed (at a rate of roughly 10 min/bead). Histiocytes ingest a non-physiologic quantity of particles, causing massive cell enlargement and loss of surface membrane veils (arrow, A). No apoptosis occurs following phagocytosis, as can be identified from the structure of the nucleus in B. m, mitochondria.

(Schneider EM, Lorenz I, Walther P, Janka-Schaub GE. Natural killer deficiency: A minor or major factor in the manifestation of hemophagocytic lymphohistiocytosis? J Pediatr Hematol Oncol 25(9):680-683, 2003.)

In-Vitro Hemophagocytosis

Ficoll-isolated peripheral blood or bone marrow derived mononuclear cells from patients with HLH are depleted from non-adherent cells by plastic adherence.  Within 2-14 days these cultures give rise to a homogeneous population of large, floating cells with a pleomorphic morphology (Fig. 1), prominent signs of autophagy, and an immature dendritic cell phenotype1. Even after 21 days of in vitro culture, residual blood cells can be detected in cultured hemophagocytes1 (Fig. 2). Cultured hemophagocytes can be membrane-stained using fluorescent dyes and tested for their interaction with NK effectors such as NK-92 cells2. Figure 3 shows that such membrane-stained NK92 (red dye) interact with cultured hemophagocytes of a patient with HLH and shortly after cell-cell contact, the NK-effectors are phagocytozed by the hemophagocyte (stained with a green membrane-dye). The phagocytic activities of such cultured hemophagocytes derived from cultures of different patients with HLH vary:  Some hemophagocytes ingest NK-92 within minutes and accumulate more than 10 NK-92 cells per hemophagocyte.

Current research activites concentrate on the analysis of the hemophagocytic specifcities of hemophagocytes derived from individual patients with HLH.

Legends:

Figure 1:
Phase contrast of cultured hemophagocyte, floating, pleomorphic morphology and veiled surface structure.


Figure 2:
Structural features of hemophagocytes. Hemophagocytes with ingested and partially digested erythrocytes (arrows) located in a distal phagosome (HLH, chemical fixation). (A). Early hemophagocytosis of another autologous hemophagocyte with remarkable autophagous vacuoles (HLH, chemical fixation) (B). Hemophagocytosis of a hemophagocyte (HLH, chemical fixation) (C). More advanced state of erythrocyte digestion in a phagosome being engulfed by another autophagosome (HLH, chemical fixation) (D). As in C, a more advanced state of phagocytosis and digestion (sepsis, chemical fixation) (E).


Figure 3:
3a shows contact formation between NK-92 (red) and hemophagocyte (green)

3b shows early hemophagocytosis of NK-92 and another NK-92 forming contact

3c shows completed phagocytosis of one NK-92 and several other NK-92 cells forming contact

References:

  1. Schneider, E., Lorenz, M, Walther, P Autophagy as a hallmark of hemophagocytic diseases. Vol. Chapter  3 (ed. Gorbunov. Nikolai (eds.), i.A.P., Regulation and Roles in Disease" ) (Nova Science Publishers, Inc.,   Cell Biology Research Progress, e-book, 2012).
  2. Yan, Y., et al. Antileukemia activity of a natural killer cell line against human leukemias. Clin Cancer Res 4, 2859-2868 (1998).

Microparticles

Under Construction

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Cellular Cytotoxicity

Under Construction

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Teaching

Degree program: Molecular Medicine (Bachelor)

Internship Immunology; Part IV (4 weeks; description part I, part II)

Degree program: Molecular Medicine (Master)

Schedule blocks (each 4-5 weeks, detailed description is in progress):  

  • “Infectious Diseases and Immune Defense” / “Trauma Research and Regenerative Medicine”
  • “Infectious Diseases and Immune Defense” jeweils 4-5 Wochen (Beschreibung wird noch erstellt).

Some publications

Book Chapters

Sander, P, Walther, P, Moepps, B, Hinz, M, Mostafa, H, Schaefer, P, Pala, A, Wirtz, CR, Georgieff, M, and Schneider, EM. 2019. Mitophagy-Related Cell Death Mediated by Vacquinol-1 and TRPM7 Blockade in Glioblastoma IV. In: OMERHODZIC, I. & ARNAUTOVIĆ, K. (eds.) Glioma - Contemporary Diagnostics and Therapeutic Approaches. IntechOpen, 81-93.

Schneider, E.M., Lorenz, M.R., Walther, P. Autophagy  as a hallmark of hemophagocytic diseases. In „Autophagy in Health and Diseases.“ (N. V. Gorbunov (ed.) NOVA Publishers N.Y. 2011.

Bruecker UB, Schneider, EM. Microarrays in der experimentellen und klinischen Forschung. In: Chirurgische Forschung; 2005, p. 304-316. Krukemeyer, MG, Spiegel, H-U (eds);Thieme Verlag, Stuttgart, New York, ISBN: 3-13-133661-7

Janka-Schaub, G., Schneider, EM. Hämophagozytische Lymphohistiozytosen. In: Pädiatrische Hämatologie und Onkologie, 2005, p231-236. Gadner, H, Gaedicke, G, Niemeyer, C, Ritter, J (eds); Springer Verlag, Heidelberg, ISBN 13 978-3-540-03702-6
 

Relevant publications, and /or products, services

Fischer, J.C., Zänker, K., van Griensven, M. et al. The role of passive immunization in the age of SARS-CoV-2: an update. Eur J Med Res 25, 16 (2020). https://doi.org/10.1186/s40001-020-00414-5

Matuschek, C., Fischer, J.C., Combs, S.E. et al. Measures of infection prevention and incidence of SARS-CoV-2 infections in cancer patients undergoing radiotherapy in Germany, Austria and Switzerland. Strahlenther Onkol (2020). https://doi.org/10.1007/s00066-020-01681-1

Matuschek, C., Moll, F., Fangerau, H. et al. Face masks: benefits and risks during the COVID-19 crisis. Eur J Med Res 25, 32 (2020). https://doi.org/10.1186/s40001-020-00430-5

Matuschek, C., Moll, F., Fangerau, H. et al. The history and value of face masks. Eur J Med Res 25, 23 (2020). https://doi.org/10.1186/s40001-020-00423-4

Gesundheit B, Ben-David E, Posen Y. Ellis R, , Wollmann G, Schneider  EM, Aigner,K,  Brauns, L, Nesselhut T, Ackva I,  Weisslein C,  Thaller A. Effective Treatment of Glioblastoma Multiforme with Oncolytic Virotherapy: A Case-Series. Frontiers in Oncology, section Cancer Molecular Targets and Therapeutics in press 2020.   Manuscript ID: 521092

Hein, T, Sander, P, Giryes, A., Reinhardt, J-O, Schneider, EM. Cytokine expression patterns and single nucleotide polymorphisms (SNPs) in patients with chronic borreliosis. Antibiotics 8:107 (2019) doi: 10.3390/antibiotics8030107

Denzinger, M, Staendker, L, Ehlers, K, Schneider, JM, Schulz, T, Hein, T, Wiese, S,  Roecker, A, Gross, R, Muench, J,  Bracht, H, Barth, E, Weiss, M, Georgieff, M,  Schneider, EM. Bioassay for Endothelial Damage Mediators Retrieved by Hemoadsorption, Sci Rep. Sci Rep 9, 14522 (2019) doi:10.1038/s41598-019-50517-1.

Walther P, Bauer A, Wenske N, Catanese A, Garrido D, Schneider EM. (2018) STEM tomography of high-pressure frozen and freeze-substituted cells: a comparison of image stacks obtained at 200 kV or 300 kV. Histochem Cell Biol. 2018 Sep 18. doi: 10.1007/s00418-018-1727-0. [Epub ahead of print]

Mack, A, Pfeiffer, C, Schneider, EM, Bechter, K. Schizophrenia or Atypical Lupus Erythematosus with Predominant Psychiatric Manifestations over 25 Years: Case Analysis and Review. Front Psychiatry. 2017 Jul 27;8:131. doi: 10.3389/fpsyt.2017.00131. eCollection 2017.

Waqas, SF, Hassnain, Hoang, AC, Lin, Y-T, Ampem, G., Azegrouz, H, Balogh, L, Thuróczy, J, Chen, J-C, Gerling, IC, Nam, S, Lim, J-S, Martínez-Ibañez, J, Real, J, Paschke, S, Quillet, R, Ayachi, S, Simonin, F, Schneider, EM, Brinkman, JA, Lamming, DW, Seroogy, CM, Röszer, T. Neuropeptide-FF increases M2 activation and self-renewal of adipose tissue macrophages. J Clin Investigation 2017 Jun 30;127(7):2842-2854. doi: 10.1172/JCI90152. Epub 2017 Jun 5. PubMed PMID: 28581443.

Current and previous projects or activities

  • EU LSH-2003-1.1.0-1 QuAGSiC “Quantitative Analysis of Genes in Single Cells” EU FP6 07.2006 – 05-2008). This Project exemplified, how infectious agents can be identified in single cells of patients with different diseases using single cell PCR. Chronic infections with intracellular pathogens play a major role ijn autoimmune dysfunction syndromes.
  • EU LSH-2003-1. 1.0-1 GenOSept “Genetics of sepsis in Europe” (EU FP6 03. 2005 – 02. 2008) Col. Functional single nucleotide polymorphisms (SNPs) play a major role in all kinds of inflammatory syndromes, the “Genetics in Sepsis “ project tought us the tools to address SNPs in autoimmune dysregulation of many other diseases, which we now follow in juvelnile rheumatoid arthritis as well as multiple sclerosis. The latter disease is most often linked to persistent borreliosis (pLB), Chlamydia, Yersinia, Rickettsia and other intracellular pathogens in addition to the preference of defined, polymorphic HLA antigens and SNPs in inflammatory cytokines such as TNF-α.
  • H2020-SC1-2016-2017: SC1-PM-02-2017 (MOODSTRATIFICATION)  Immune Signatures for Therapy Stratification in Major Mood Disorders. Within this project, immune signatures of patients with psychosis are recruited and studied for pathogen vs. autoimmune characteristics. The cytokine and cell profiling is performed in peripheral blood ans well as in cerebrospinal fluid (CSF).
  • Collaborative Project with Stephen Fuller (Department of Intensive Care Medicine, Nepean Hospital Clinical School, Univ. Sydney, Australia) and Marek Nalos (Medical ICU, Pilzen, Czech Republic) on P2X7 SNPs in survivors and non-survivors with sepsis and septic shock.
  • Nanoparticle based therapeutics in fungal infections (John Luong and Jeremy D Glennon, Cork Univ. College, School of Chemistry, Ireland.
  • VirA  WIDESPREAD-05-2020 CSA: Reducing networking gaps between Rīga Stradiņš University (RSU) and internationally – leading counterparts in viral infection-induced autoimmunity research”
    Major impact and work in Ulm addresses the IMMUNOLOGY PLATFORM undergraduate and graduate students managements and knowledge dissemination using approproiate materials of autoimmune diseases related to viral infections. Project duration: Dec. 2020 – Dec 2023

Significant infrastructure / technical equipment

The Division of Experimental Anesthesiology is a fully equipped immunological laboratory, including access to mass spectroscopy, electron microscopy and single cell analysis, as well as patients’ records and material from a full spectrum of diseases with autoimmune disorders all collected in clinical studies. Archived material of viable cells, plasma and DNA is available from more than 20,000 individuals. Confocal microscopy, chemiluminescence based ELISA, qPCR, microparticle enrichment and characterization, following inflammasome activation are important tools to study autoimmune diseases and neurological disorders including PTSD. An ongoing study performed within the MOODSTRATIFICATION project addresses autoimmune dysfunction in patients with psychosis and a possible involvement of HSV1. The cell types in focus are monocytes (M1, M2), dendritic cells and naïve and different memory T lymphocytes.

Operational capacity

Is sufficient to cooperate on national as well as international in scientific and technical and mathematical projects.

Collaborations

  • Dr. Thomas Joos, Dr. Nicole Schneiderhahn-Marra (Naturwissenschaftlich Medizinisches Institut Reutlingen, Universität Tübingen) „Clustering of Cytokinexpression patterns in patients with Trauma, Sepsis and Shock“. Peptide Ligand Assay develoments (Cathelicidines, defensins).
  • Dr. Manfred Schmolz (Hotscreen GmbH, Reutlingen, Germany) Application and further developement of ex-vivo whole blood assays, TruCulture®.
  • Prof. Dr. Knut M. Wittkowski (Rockefeller University, Center for Clinical and Translational Science (CCTS), N.Y., USA) Biomarker-based clinical scores, genome wide association studies.
  • Kim, Hyung-Suk (NIH/NINR USA,  Bethesda, USA) GWAS in fibromyalgia.
  • Dr. Sandeep Kumar Vashist (Global IVD Director at Pictor Biotechnology, Auckland, New Zea Land) Development of PoC devices.
  • Prof. Dr. Hsin-Yun HSU (Department of Applied Chemistry/Institute of Molecular Science National Chiao; Tung University,  Hsinchu 30010, Taiwan) Carbon nanotubes in immature dendritic cells.
Profilbild von Prof. Dr. rer. nat. E. Schneider

Prof. Dr. rer. nat. E. Schneider

Sektionsleiterin Experimentelle Anästhesiologie | Head of the Division Experimental Anesthesiology