Head

Photo of Prof. Klaus-Michael Debatin standing in a corridor of the hospital

Prof. Dr. Klaus-Michael Debatin

Ulm University Medical Center
Department of Pediatrics and Adolescent Medicine
Eythstr. 24
89075 Ulm, Germany

phone: +49-731-500-57001
fax: +49-731-500-57002

e-mail:
klaus-michael.debatin@uniklinik-ulm.de

Contact at the Glioblastoma Lab

apl. Prof. Dr. Mike-Andrew Westhoff
Co-Head of Group

phone: +49-731-500-57495
fax: +49-731-500-57042

e-mail:
andrew.westhoff@uniklinik-ulm.de

Research Profile

A special focus within the different activities of Klaus-Michael Debatin (see his scientific profile for an overview) is on understanding mechanisms of sensitivity and resistance of tumour cells for anticancer therapy. This also includes the analysis of signalling pathways that may help to overcome resistance to molecular targeted therapy or conventional therapy using cytotoxic drugs and irradiation in human and particularly in paediatric tumours. Glioblastoma is of particular interest and investigated in the group together with Dr. Mike-Andrew Westhoff presented on this web page.

The main focus of this group's cancer therapy and apoptosis research lies with Glioblastoma which is among the most lethal tumours encountered in the clinic. It is the most frequent primary brain tumour in adults and is also not uncommon in children. Successful therapy, consisting of maximal safe surgical resection, radio- and chemotherapy, only extents life expectancy to 15 months.

Our research group focuses on three areas of interest:

Two glioblastoma cells. Actin was stained with TRIC-phalloidin. The left glioblastoma cell clearly exhibits a well-structured cytoskeleton. In the right cell, a signalling pathway has been blocked, which hitherto had not been considered to be connected with cell organization and motility. The destruction of F-actin fibres can clearly be seen.
Actin was stained with TRIC-phalloidin. The left glioblastoma cell clearly exhibits a well-structured cytoskeleton. In the right cell, a signalling pathway has been blocked, which hitherto had not been considered to be connected with cell organization and motility. The destruction of F-actin fibres can clearly be seen. Photos: Claudia Jennewein [1]

Unusual for such an aggressive disease Glioblastoma has relatively few distinct mutations and other genetic alterations, presenting the researcher with few druggable targets. Among those is the PI3K signalling cascade that is activated in ~90% of all Glioblastoma. Understanding the role of this signalling network in different cell populations of the tumour and elucidating the therapeutic potential of pathway inhibition has led new therapeutic avenues implemented in our clinic. [2]

Due to the unique features of Glioblastoma (see below) it is not sufficient to target the tumour bulk as malignant cells will have already spread throughout the brain. Therapeutic approaches to target those cells are rather limited due to the blood-brain-barrier which prevents the free distribution of drugs throughout the brain. Hence novel approaches, drug combinations or treatment regiments are needed to over come these limitations. Such as the RIST therapy, which was developed in this clinic and is used in a compassionate use setting. [3]

Glioblastoma only rarely metastasises outside the CNS but seems to not exist in a pre-invasive form. Understanding the underlying molecular mechanisms will help us to modulate the invasive nature of the Glioblastoma cells and transform it into a more localised, i.e. easier to treat disease. We have formulated the so-called Alcatraz Strategy that aims to prevent the interaction/communication of cancer cells with their environment. [4]

Taking these three aspects together gives us a clear aim of our research: By combining basic research and bidirectional translational research to improve our understanding how to a) target the unique features of Glioblastoma and b) adapt novel treatment approaches for their implementation in Glioblastoma treatment.

To answer these questions we have created a collection of ~300 case files with ~100 stored tumour samples and ~50 patient-derived cell populations.

  1. Westhoff MA, Zhou S, Nonnenmacher L, Karpel-Massler G, Jennewein C, Schneider M, Halatsch ME, Carragher NO, Baumann B, Krause A, Simmet T, Bachem MG, Wirtz CR, Debatin KM. Inhibition of NF-κB signaling ablates the invasive phenotype of glioblastoma. Mol Cancer Res. 2013 Dec; 11(12):1611-23.
  2. Langhans J, Schneele L, Trenkler N, von Bandemer H, Nonnenmacher L, Karpel-Massler G, Siegelin MD, Zhou S, Halatsch ME, Debatin KM, Westhoff MA. The effects of PI3K-mediated signalling on glioblastoma cell behaviour. Oncogenesis. 2017 Nov 29; 6(11):398.
  3. Nonnenmacher L, Westhoff MA, Fulda S, Karpel-Massler G, Halatsch ME, Engelke J, Simmet T, Corbacioglu S, Debatin KM. RIST: a potent new combination therapy for glioblastoma. Int J Cancer. 2015 Feb 15; 136(4):E173-87.
  4. Mettang M, Meyer-Pannwitt V, Karpel-Massler G, Zhou S, Carragher NO, Föhr KJ, Baumann B, Nonnenmacher L, Enzenmüller S, Dahlhaus M, Siegelin MD, Stroh S, Mertens D, Fischer-Posovszky P, Schneider EM, Halatsch ME, Debatin KM, Westhoff MA. Blocking distinct interactions between Glioblastoma cells and their tissue microenvironment: A novel multi-targeted therapeutic approach. Sci Rep. 2018 Apr 3; 8(1):5527.

Our research on glioblastoma was financially supported by:

For additional grants attracted by Klaus-Michael Debatin see Meyer/Debatin Group and BIU.

Here is a selection of publications related to our glioblastoma focus:

  1. Mettang M, Meyer-Pannwitt V, Karpel-Massler G, Zhou S, Carragher NO, Föhr KJ, Baumann B, Nonnenmacher L, Enzenmüller S, Dahlhaus M, Siegelin MD, Stroh S, Mertens D, Fischer-Posovszky P, Schneider EM, Halatsch ME, Debatin KM, Westhoff MA. Blocking distinct interactions between Glioblastoma cells and their tissue microenvironment: A novel multi-targeted therapeutic approach. Sci Rep. 2018 Apr 3; 8(1):5527.
  2. Westhoff MA, Marschall N, Grunert M, Karpel-Massler G, Burdach S, Debatin KM. Cell death-based treatment of childhood cancer. Cell Death Dis. 2018 Jan 25; 9(2):116.
  3. Langhans J, Schneele L, Trenkler N, von Bandemer H, Nonnenmacher L, Karpel-Massler G, Siegelin MD, Zhou S, Halatsch ME, Debatin KM, Westhoff MA. The effects of PI3K-mediated signalling on glioblastoma cell behaviour. Oncogenesis. 2017 Nov 29; 6(11):398.
  4. Schneider M, Ströbele S, Nonnenmacher L, Siegelin MD, Tepper M, Stroh S, Hasslacher S, Enzenmüller S, Strauss G, Baumann B, Karpel-Massler G, Westhoff MA, Debatin KM, Halatsch ME. A paired comparison between glioblastoma "stem cells" and differentiated cells. Int J Cancer. 2016 Apr 1; 138(7):1709-18.
  5. Ströbele S, Schneider M, Schneele L, Siegelin MD, Nonnenmacher L, Zhou S, Karpel-Massler G, Westhoff MA, Halatsch ME, Debatin KM. A Potential Role for the Inhibition of PI3K Signaling in Glioblastoma Therapy. PLoS One. 2015 Jun 29; 10(6):e0131670.
  6. Nonnenmacher L, Westhoff MA, Fulda S, Karpel-Massler G, Halatsch ME, Engelke J, Simmet T, Corbacioglu S, Debatin KM. RIST: a potent new combination therapy for glioblastoma. Int J Cancer. 2015 Feb 15; 136(4):E173-87.
  7. Westhoff MA, Faham N, Marx D, Nonnenmacher L, Jennewein C, Enzenmüller S, Gonzalez P, Fulda S, Debatin KM. Sequential dosing in chemosensitization: targeting the PI3K/Akt/mTOR pathway in neuroblastoma. PLoS One. 2013 Dec 31; 8(12):e83128.
  8. Westhoff MA, Zhou S, Nonnenmacher L, Karpel-Massler G, Jennewein C, Schneider M, Halatsch ME, Carragher NO, Baumann B, Krause A, Simmet T, Bachem MG, Wirtz CR, Debatin KM. Inhibition of NF-κB signaling ablates the invasive phenotype of glioblastoma. Mol Cancer Res. 2013 Dec; 11(12):1611-23.
  9. Westhoff MA, Kandenwein JA, Karl S, Vellanki SH, Braun V, Eramo A, Antoniadis G, Debatin KM, Fulda S. The pyridinylfuranopyrimidine inhibitor, PI-103, chemosensitizes glioblastoma cells for apoptosis by inhibiting DNA repair. Oncogene. 2009 Oct 8; 28(40):3586-96.
  10. Westhoff MA, Zhou S, Bachem MG, Debatin KM, Fulda S. Identification of a novel switch in the dominant forms of cell adhesion-mediated drug resistance in glioblastoma cells. Oncogene. 2008 Sep 4; 27(39):5169-81.

For additional publications by Klaus-Michael Debatin see ORCID and the selected publications in his CV.