RG Müller

Medicine 5

Head of Department:
Prof. Dr. med. Andreas Mackensen

RG Müller - Laboratory of Molecular Immunotherapy (LMIT)

Team AG Müller

 Franziska Wagner, Dr. Fabian Müller, Charlotte Wagner

Research Focus:

Recombinant immunotoxins (rIT) are fusion proteins of an antibody and Pseudomonas exotoxin A (PE, Figure 1).  The antibody directs the rIT selectively towards tumor cells while healthy tissue remains unaffected.  After binding, the rIT is internalized, traverses various intracellular compartments, and ADP-ribosylates EF2 in the cytosol; protein synthesis is arrested and cells activate their cell death program (Figure 2).

Our young research group focuses on the immune activating effects induced when specifically killing cancer cells with rIT.  Goal of our research is to understand the molecular and cellular mechanism behind the specific anti-cancer immune activation in syngeneic animal model systems.

In addition to working with existing rIT developed by Dr. Ira Pastan, LMB, NCI, NIH, USA, our group works on new targets for conventional rITs and on novel toxin concepts to further improve their efficacy against cancer.

Collaborations:

internal:

  • Prof. Dr. Jäck (Head, Dept. for Molecular Immunology)
  • Prof. Dr. Nitschke (Biology, Head, Division of Genetics)
  • Prof. Dr. Rauh (Children’s Hospital, Head, Devision of Routine Diagnostics)

external:

  • Dr. Ira Pastan, National Institutes of Health, Bethesda, MD, USA
  • Dr. Terry Fry, National Institutes of Health, Bethesda, MD, USA
  • Dr. Alan S. Wayne, Children's Hospital Los Angeles, CA, USA
  • Medimmune, LLC,  Gaithersburg, MD, USA

 

Selected Publications:

Mueller, F., Cunningham, T., Liu, X., Wayne, A. S. & Pastan, I. Wide variability in the time required for immunotoxins to kill B lineage acute lymphoblastic leukemia cells: Implications for trial design. Clin. Cancer Res., doi:10.1158/1078-0432.CCR-15-2500 (2016).

Liu, X.*, Mueller, F.*, Wayne, A. S. & Pastan, I. Protein kinase inhibitor H89 enhances the activity of Pseudomonas exotoxin A-based immunotoxins. Mol. Cancer Ther., doi:10.1158/1535-7163.MCT-15-0828 (2016).

Hollevoet K, Mason-Osann E, Müller F, Pastan I. Methylation-associated partial down-regulation of mesothelin causes resistance to anti-mesothelin immunotoxins in a pancreatic cancer cell line. PLosONE. Mar 24;10(3):e0122462. doi: 10.1371/journal.pone.0122462 (2014).

 
Contact
Dr. med. Fabian Müller
DECT: +49 9131 85-39542
fax: +49 9131 85-39546
e-mail: fabian.mueller@uk-erlangen.de
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Summary