Visual Universitätsmedizin Mainz

Nadine Müller-Calleja, PhD

Müller-Calleja, PhD
Nadine Müller-Calleja, PhD
Position: Post Doc, Virchow Fellow

06131 17-5083 oder 17-2606
nadine.mueller-calleja@unimedizin-mainz.de
Further Information

Project description

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by recurrent venous and/or arterial thrombosis or fetal loss associated with persistently elevated titers of antiphospholipid antibodies (aPLs). It has been known for over 20 years that aPL are causally involved in the pathogenesis of APS. However, the underlying signaling pathway is only partially understood.

I will focus on the characterization of the underlying cellular mechanisms. We could recently show that aPL activate an endosomal NADPH oxidase in different cell types. This increases the risk of thrombosis in patients. A detailed elucidation of the precise mechanisms by which aPL cause thrombosis promises a better understanding of APS pathogenesis and might provide new targets for the development of therapeutic strategies.

Research Interests

  • Pathogenesis of Antiphospholipid Syndrome
  • Activation and assembly of endosomal NADPH oxidase
  • Role of endosmal NADPH oxidase in innate immunity
  • Translocation of intracellular toll-like receptors

Research Funding

  • MAIFOR

Team

  • Antonia Köhler (Master Student)
  • Antje Canisius (MTA)
  • Carolin Orning (MTA)

Mentor

Mentor of the Virchow-Fellow is Professor Karl J. Lackner, MD, Director of the Institute of Clinical Chemistry and Laboratory Medicine.

Curriculum vitae

09/1995-03/2004

Eichendorff-Gymnasium, Koblenz

04/2004-06/2006

Bachelor of Science “Molecular Biology”, University of Mainz

07/2006-10/2006

Internship at Life & Brain GmbH, Bonn

10/2006-07/2008

Master of Science “Biomedicine”, University of Mainz

08/2008-12/2008

Internship at Sanofi-Aventis Deutschland GmbH, Science and Medical Affairs, Frankfurt am Main

01/2009-09/2011

Promotion: “Signaling transduction of IgG Antiphospholipid antibodies in Plasmacytoid dendritic cells and MonoMac-1 cells” at the Institute of Clinical Chemistry and Laboratory Medicine, Mainz, Prof. Dr. Karl J. Lackner

seit 09/2011

Research Associate of the Institute of Clinical Chemistry and Laboratory Medicine

References

  • Lackner KJ, Manukyan D, Müller-Calleja N (2017) Pathophysiological insights into the antiphospholipid syndrome. Hamostaseologie 37: 202-207
  • Manukyan D, Müller-Calleja N, Jäckel S, Luchmann K, Monnikes R, Kiouptsi K, Reinhardt C, Jurk K, Walter U, Lackner KJ. Cofactor-independent human antiphospholipid antibodies induce venous thrombosis in mice. Journal of thrombosis and haemostasis 14:1011-1020. 2016.
  • Müller-Calleja N, Kohler A, Siebald B, Canisius A, Orning C, Radsak M, Stein P, Monnikes R, Lackner KJ. Cofactor-independent antiphospholipid antibodies activate the NLRP3-inflammasome via endosomal NADPH-oxidase: implications for the antiphospholipid syndrome. Thrombosis and haemostasis 113:1071-1083, 2015.
  • Prinz N, Clemens N, Canisius A, Lackner KJ: Endosomal NADPH-Oxidase is critical for induction of the tissue factor gene in monocytes and endothelial cells - lessons from the antiphospholipid syndrome. Thrombosis and Haemostasis. 2013 Mar 5;109(3):525-31.
  • Gladigau G, Haselmayer P, Scharrer I, Munder M, Prinz N, Lackner K, Schild H, Stein P, Radsak MP: a role for Toll-like receptor mediated signals in neutrophils in the pathogenesis of the anti-phospholipid syndrome. PLoS One. 2012;7(7):e42176. Epub 2012 Jul 31.
  • Prinz N, Clemens N, Strand D, Pütz I, Lorenz M, Daiber A, Stein P, Degreif A, Rad- sak M, Schild H, Bauer S, von Landenberg P, Lackner KJ: Antiphospholipid antibod- ies induce translocation of TLR7 and TLR8 to the endosome in human monocytes and plasmacytoid dendritic cells. Blood. 2011 Aug 25;118(8):2322-32.
  • Prinz N, Häuser F, Lorenz M, Lackner KJ, von Landenberg P: Structural and func- tional characterization of a human IgG monoclonal antiphospholipid antibody. Im- munobiology. 2011 Jan-Feb;216(1-2):145-51.
  • Hurst J, Lorenz M, Prinz N, von Landenberg P: The roll of Toll-like receptors in the antiphospholipid syndrome. Curr Rheumatol Rep. 2010 Feb;12(1):58-63. Review. 
  • Döring Y, Hurst J, Lorenz M, Prinz N, Clemens N, Drechsler MD, Bauer S, Chapman J, Shoenfeld Y, Blank M, Lackner KJ, von Landenberg P: Human antiphospholipid antibodies induce TNFalpha in monocytes via Toll-like receptor 8. Immunobiology. 2010 Mar;215(3):230-41. 
  • Hurst J*, Prinz N*, Lorenz M, Bauer S, Chapman J, Lackner KJ, von Landenberg P: TLR7 and TLR8 ligands and antiphospholipid antibodies show synergistic effects on the induction of IL-1beta and caspase-1 in monocytes and dendritic cells. Immunobi- ology. 2009;214(8):683-91. *Equal contribution