Wissen schafft Heilung.

 

Tumor-associated Proteolysis (Magdolen Lab)

Principal investigator

Prof. Dr. rer. nat. Viktor Magdolen, Ph.D.
Klinische Forschergruppe der Frauenklinik
Klinikum rechts der Isar der Technischen Universität München
Tel.: (089) 4140-2493
Fax: (089) 4140-7410
E-Mail: viktor.magdolen@tum.de
 

Lab members

     •  Viktor Magdolen, Prof. Dr. rer. nat.    
     •  Manfred Schmitt, Prof. Dr. rer. nat., Emeritus of Excellence der TUM †
     •  Caixia Zhu, Sun Yat-Sen University, China
     •  Sabine Creutzburg, CTA
     •  Daniela Hellmann, VMTLA
     •  Weiwei Gong
     •  Xiaocong Geng
     •  Yueyang Liu
     •  Johanna Felber
     •  Larissa Dettmar
     •  Tom Schulze

Research Background

Biochemical and structural analyses of tumor-associated serine proteases, their inhibitors and receptors

  • Recombinant expression in E. coli, purification and re-folding of the human / rodent proteins
  • Enzymatic characterization of tumor-associated proteases
  • Synthetic and natural inhibitors
  • Urokinase receptor (uPAR) and CUB domain containing protein 1 (CDCP1) as target for radiotherapy

Clinical relevance of biomarkers in solid tumors

  • Establishment of quantitative PCR assays, immunohistochemistry, and ELISAs
  • Generation of antibodies
  • Biomarkers analyzed:
  • Components of the urokinase system (uPA, PAI-1, uPAR and its splice variant uPAR-del4/5, plasmin(ogen) / angiostatin
  • Kallikrein-related peptidases (KLK1-KLK15)
  • Vesicular transport protein Rab31
  • Therapy-relevant genes and miRNAs

Tumor biology of selected biomarkers

  • Tumor biological role of the GTP-binding protein Rab31
  • Modulation of the expression of selected KLK proteases in ovarian and prostate cancer cells: analysis of the effects on proliferation, migration, adhesion, invasion and gene expression of other tumor-relevant genes

 

Selected publications

Loessner D, Goettig P, Preis S, Felber J, Bronger H, Clements JA, Dorn J, Magdolen V (2018) Kallikrein-related peptidases represent attractive therapeutic targets for ovarian cancer. Expert Opin Ther Targets 22:745-63

Wang P, Magdolen V, Seidl C, Dorn J, Drecoll E, Kotzsch M, Yang F, Schmitt M, Schilling O, Rockstroh A, Clements JA, Loessner D (2018) Kallikrein-related peptidases 4, 5, 6 and 7 regulate tumour-associated factors in serous ovarian cancer. Br J Cancer 119:823-31

Debela M*, Magdolen V*, Skala W, Elsässer B, Schneider EL, Craik CS, Biniossek ML, Schilling O, Bode W, Brandstetter H, Goettig P (2018) Structural determinants of specificity and regulation of activity in the allosteric loop network of human KLK8/neuropsin. Sci Rep 8:10705; *contributed equally

Begcevic I, Brinc D, Brown M, Martinez-Morillo E, Goldhardt O, Grimmer T, Magdolen V, Batruch I, Diamandis EP (2018) Brain-related proteins as potential CSF biomarkers of Alzheimer's disease: A targeted mass spectrometry approach. J Proteomics 182:12-20.

Dettmar L, Ahmed N, Kotzsch M, Diersch S, Napieralski R, Darmoul D, Schmitt M, Weichert W, Kiechle M, Dorn J, Magdolen V (2018) Advanced high-grade serous ovarian cancer: inverse association of KLK13 and KLK14 mRNA levels in tumor tissue and patients’ prognosis. J Cancer Res Clin Oncol 144:1109-18

Delaunay T,  L, Haddada M, Walker F, Soosaipillai A, Soualmia F,  El Amri C, Diamandis EP, Brattsand M, Magdolen V*, Darmoul D* (2017) Aberrant expression of kallikrein-related peptidase 7 is correlated to human melanoma aggressiveness by stimulating cell migration and invasion. Mol Oncol 11:1330-47; *contributed equally

Kotzsch M, Kirchner T, Soelch S, Schäfer S, Friedrich K, Baretton G, Magdolen V, Luther T (2017) Inverse association of rab31 and mucin-1 (CA15-3) antigen levels in estrogen receptor-positive (ER+) breast cancer tissues with clinicopathological parameters and patients' prognosis. Am J Cancer Res 7:1959-70

Guo S, Skala W, Magdolen V, Briza P, Biniossek ML, Schilling O, Kellermann J, Brandstetter H, Goettig P (2016) A single glycan at the 99-loop of human kallikrein-related peptidase 2 regulates activation and enzymatic activity. J Biol Chem 291:593-604

Falkenberg N, Anastasov N, Schaub A, Radulovic V, Schmitt M, Magdolen V, Aubele M (2015) Secreted uPAR isoform 2 (uPAR7b) is a novel direct target of miR-221. Oncotarget 10:8103-14

Dorn J, Beaufort N, Schmitt M, Diamandis EP, Goettig P, Magdolen V (2014) Function and clinical relevance of kallikrein-related peptidases and other serine proteases in gynecological cancers. Crit Rev Clin Lab Sci 51:63-84

Loessner D, Rizzi SC, Stok KS, Fuehrmann T, Hollier B, Magdolen V, Hutmacher DW, Clements JA (2013) A bioengineered 3D ovarian cancer model highlights kallikrein–related peptidase–mediated enhancement of spheroid growth and intraperitoneal spread. Biomaterials 34:7389-7400

A complete list of publications can be found here.
 

Medical or M.Sc. theses

Interested students are welcome to contact Prof. Magdolen via e-mail or to drop by the experimental laboratory.
 

Grant support

  • German Research Foundation (DFG)
  • German Cancer Aid (Deutsche Krebshilfe)
  • German Ministry of Education and Science (BMBF)
  • German Academic Exchange Service (DAAD)
  • Alexander von Humboldt-Foundation
  • Bavarian Research Foundation (Bayerische Forschungsschulstiftung)
  • EU Socrates / Erasmus / Madame Curie Training Site Programs
  • Kommission für klinische Forschungsprojekte der TUM (KKF)
  • Centre de Coopération Universitaire Franco-Bavarois (CCUFB)
  • Centro Universitario de Baviera para América Latina (BAYLAT)
  • Collaborations with biotech companies (Therawis GmbH, Spherotec GmbH, Wilex AG, American Diagnostica Inc.)

 

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