III. Medizinische Klinik (Hämatologie und Onkologie)

Molecular Immunopathology & Signal Transduction


Prof. Dr. rer. nat. Marc Schmidt-Supprian
Head of Research at the III. Medizinische Klinik
III. Medizinische Klinik
Klinikum rechts der Isar
Technische Universität München

Phone (office): 089 /4140-4104
Phone (Lab): 089 /4140-2668
Fax: 089 / 4140-4879


Tim Ammon (Postdoc, also AG Ringshausen)
Yuanyuan Chu (Postdoc)
Christoph Drees (PhD student)
Barbara Habermehl (Technician)
Klaus Heger (Postdoc)
Julia Knogler (Technician)
Maike Kober (PhD student)
David Riess (PhD student)
Valeria Soberon (PhD student)
Claudia Mugler (shared with III. Med groups)

Research synopsis:

Our group is interested in elucidating the molecular regulation of immune cell development and function through genetic loss and gain of function approaches in the mouse. We investigate B and T lymphocytes and mast cells. Our particular interest is on proteins whose exaggerated functions or malfunctions directly contribute to immunpathologies, such as lymphomas/leukemais, autoimmunity and allergies.
In the context of NF-kB signal transduction we currently focus on the ubiquitin editing enzyme A20/TNFAIP3 and the transcription factor c-Rel. Another central topic is the regulation of mRNA stability by the RING finger proteins Roquin1/2. In addition, we are investigating the role of T cell receptor-expression and signaling on immune-modulating regulatory T (TR) cells and lipid-recognizing NK-like T (NKT) cells.

Selected publications:

For a full publication list see: http://www.ncbi.nlm.nih.gov/pubmed/?term=schmidt-supprian and http://www.researcherid.com/rid/F-5893-2011

TCR signals fuel Treg cells.
Drees C, Vahl JC, Schmidt-Supprian M.
Oncotarget. 2015 Jul 12.

A novel Cre recombinase reporter mouse strain facilitates selective and efficient infection of primary immune cells with adenoviral vectors
Klaus Heger, Maike Kober, David Rieß, Christoph Drees, Ingrid de Vries, Arianna Bertossi, Axel Roers, Michael Sixt and Marc Schmidt-Supprian
European Journal of Immunology 2015 Jun;45(6):1614-20.

Continuous T Cell Receptor Signals Maintain a Functional Regulatory T Cell Pool.
Vahl JC, Drees C, Heger K, Heink S, Fischer JC, Nedjic J, Ohkura N, Morikawa H, Poeck H, Schallenberg S, Rieß D, Hein MY, Buch T, Polic B, Schönle A, Zeiser R, Schmitt-Gräff A, Kretschmer K, Klein L, Korn T, Sakaguchi S, Schmidt-Supprian M.
Immunity. 2014 Nov 6;41(5):722-736.

IκB Kinase 2 Is Essential for IgE-Induced Mast Cell De Novo Cytokine Production but Not for Degranulation.
Peschke K, Weitzmann A, Heger K, Behrendt R, Schubert N, Scholten J, Voehringer D, Hartmann K, Dudeck A, Schmidt-Supprian M*, Roers A*:
Cell Reports 2014, 8:1300–1307.   
*Corresponding authors

A20-deficient mast cells exacerbate inflammatory responses in vivo.
Heger K*, Fierens K*, Vahl JC, Aszodi A, Peschke K, Schenten D, Hammad H, Beyaert R, Saur D, van Loo G, Roers A, Lambrecht BN, Kool M, Schmidt-Supprian M:
PLoS Biol 2014, 12:e1001762.         
*Equal contribution

CreER(T2) expression from within the c-Kit gene locus allows efficient inducible gene targeting in and ablation of mast cells.
Heger K, Seidler B, Vahl JC, Schwartz C, Kober M, Klein S, Voehringer D, Saur D*,Schmidt-Supprian M*:
Eur J Immunol 2014, 44:296–306.
*Equal contribution

NKT cell-TCR expression activates conventional T cells in vivo, but is largely dispensable for mature NKT cell biology.
Vahl JC, Heger K, Knies N, Hein MY, Boon L, Yagita H, Polic B, Schmidt-Supprian M:
PLoS Biol 2013, 11:e1001589.

Roquin Paralogs 1 and 2 Redundantly Repress the Icos and Ox40 Costimulator mRNAs and Control Follicular Helper T Cell Differentiation.
Vogel KU, Edelmann SL, Jeltsch KM, Bertossi A, Heger K, Heinz GA, Zöller J, Warth SC, Hoefig KP, Lohs C, Neff F, Kremmer E, Schick J, Repsilber D, Geerlof A, Blum H, Wurst W, Heikenwalder M, Schmidt-Supprian M*, Heissmeyer V*:
Immunity 2013, 38:655–668.
*Corresponding authors

A20 and CYLD Do Not Share Significant Overlapping Functions during B Cell Development and Activation.
Chu Y, Soberon V, Glockner L, Beyaert R, Massoumi R, van Loo G, Krappmann D, Schmidt-Supprian M:
J Immunol 2012, 189:4437–4443.

Loss of Roquin induces early death and immune deregulation but not autoimmunity.
Bertossi A, Aichinger M, Sansonetti P, Lech M, Neff F, Pal M, Wunderlich FT, Anders H-J, Klein L, Schmidt-Supprian M:
J Exp Med 2011, 208:1749–1756.

B cells lacking the tumor suppressor TNFAIP3/A20 display impaired differentiation and hyperactivation and cause inflammation and autoimmunity in aged mice.
Chu Y, Vahl JC, Kumar D, Heger K, Bertossi A, Wójtowicz E, Soberon V, Schenten D, Mack B, Reutelshöfer M, Beyaert R, Amann K, van Loo G, Schmidt-Supprian M:
Blood 2011, 117:2227–2236.

Development of immunoglobulin lambda-chain-positive B cells, but not editing of immunoglobulin kappa-chain, depends on NF-kappaB signals.
Derudder E*, Cadera EJ, Vahl JC, Wang J, Fox CJ, Zha S, van Loo G, Pasparakis M, Schlissel MS, Schmidt-Supprian M#*, Rajewsky K#*:
Nat Immunol 2009, 10:647–654.
*Corresponding authors, #Equal contribution

NIK overexpression amplifies, whereas ablation of its TRAF3-binding domain replaces BAFF:BAFF-R-mediated survival signals in B cells.
Sasaki Y*, Calado DP, Derudder E, Zhang B, Shimizu Y, Mackay F, Nishikawa S-I, Rajewsky K#*, Schmidt-Supprian M#*:
Proc Natl Acad Sci USA 2008, 105:10883–10888.
*Corresponding authors, #Equal contribution

Excision of the Frt-flanked neo (R) cassette from the CD19cre knock-in transgene reduces Cre-mediated recombination.
Schmidt-Supprian M*
, Wunderlich FT, Rajewsky K:
Transgenic Res 2007, 16:657–660.
*Corresponding author

I kappa B kinase 2/beta deficiency controls expansion of autoreactive T cells and suppresses experimental autoimmune encephalomyelitis.
Greve B, Weissert R, Hamdi N, Bettelli E, Sobel RA, Coyle A, Kuchroo VK, Rajewsky K, Schmidt-Supprian M:
J Immunol 2007, 179:179–185.

Vagaries of conditional gene targeting.
Schmidt-Supprian M*
, Rajewsky K*:
Nat Immunol 2007, 8:665–668.
*Corresponding authors

Epithelial NF-kappaB maintains host gut microflora homeostasis.
Ben-Neriah Y, Schmidt-Supprian M:
Nat Immunol 2007:479–481.

Canonical NF-kappaB activity, dispensable for B cell development, replaces BAFF-receptor signals and promotes B cell proliferation upon activation
Sasaki Y*, Derudder E, Hobeika E, Pelanda R, Reth M, Rajewsky K*, Schmidt-Supprian M*:
Immunity 2006, 24:729–739.
*Corresponding authors

Dissection of the NF-kappaB signalling cascade in transgenic and knockout mice.
Pasparakis M, Luedde T, Schmidt-Supprian M:
Cell Death Differ 2006, 13:861–872.

TNF family member B cell-activating factor (BAFF) receptor-dependent and -independent roles for BAFF in B cell physiology.
Sasaki Y*, Casola S, Kutok J, Rajewsky K, Schmidt-Supprian M*:
J Immunol 2004, 173:2245–2252.
*Corresponding authors

I kappa B kinase 2 deficiency in T cells leads to defects in priming, B cell help, germinal center reactions, and homeostatic expansion.
Schmidt-Supprian M*
, Tian J, Ji H, Terhorst C, Bhan A, Grant E, Pasparakis M, Casola S, Coyle A, Rajewsky K:
J Immunol 2004, 173:1612–1619.
*Corresponding author

Differential dependence of CD4+CD25+ regulatory and natural killer-like T cells on signals leading to NF-kappaB activation.
Schmidt-Supprian M
, Tian J, Grant EP, Pasparakis M, Maehr R, Ovaa H, Ploegh HL, Coyle AJ, Rajewsky K:
Proc Natl Acad Sci USA 2004, 101:4566–4571.

Mature T cells depend on signaling through the IKK complex.
Schmidt-Supprian M
, Courtois G, Tian J, Coyle A, Israel A, Rajewsky K, Pasparakis M:
Immunity 2003, 19:377–389.

IkappaB kinase signaling is essential for maintenance of mature B cells.
Pasparakis M#, Schmidt-Supprian M#, Rajewsky K:
J Exp Med 2002, 196:743–752.
#Equal contribution

Activated protein C inhibits tumor necrosis factor and macrophage migration inhibitory factor production in monocytes.
Schmidt-Supprian M
, Murphy C, While B, Lawler M, Kapurniotu A, Voelter W, Smith O, Bernhagen J:
Eur Cytokine Netw 2000, 11:407–413.

NEMO/IKK gamma-deficient mice model incontinentia pigmenti.
Schmidt-Supprian M*
, Bloch W, Courtois G, Addicks K, Israel A, Rajewsky K, Pasparakis M*:
Mol Cell 2000, 5:981–992.
*Corresponding authors

Prof. Dr. rer. nat. Marc Schmidt-Supprian

2010 · III. Medizinische Klinik (Hämatologie / Onkologie) am Klinikum rechts der Isar der Technischen Universität München