Group name: BWK Brain Cancer Research group
Group leader: Bjarne Winther Kristensen
Group members: Total 12; 1 post doc (50%), 2 PhD students, 2 MSc students, 5 pregraduate MSc/MD students, 1 technician
Department & University/Hospital/Other:
Department of Pathology, OUH
Department of Clinical Research, SDU
Funding sources:
FSS, Novo Nordic Foundation, Danish Cancer Society, several private foundations
Description of research (please divide into main projects):
1) Influence of tumor microenvironment on therapeutic resistance
2) Inlfuence of tumor-brain interaction on tumor development and therapeutic resistance
3) Identification of novel biomarkers by experimental discovery stragegies combined with studies in clinical patient cohorts
4) Integreated brain tumor diagnostics with microscopy, next-generation sequencing and genome-wide methylation profiling.
Key publications (last 10 years):
S. Munthe, B. Halle, H.B. Boldt, H. Christiansen, S. Schmidt, V. Kaimal, J. Xu, S. Zabludoff, J. Mollenhauer, F.R. Poulsen, B.W. Kristensen. Shift of microRNA profile upon glioma cell mi-gration using patient-derived spheroids and serum-free conditions. J Neurooncol 2017, Jan 13, Epub ahead of print. PMID: 28091986
H. Thisgaard*, B. Halle*, C. Aaberg-Jessen, B.B. Olsen, A.S. Therkelsen, J.H. Dam, N. Langkjær, S. Munthe, K. Någren, P.F. Høilund-Carlsen*, B.W. Kristensen*. Highly effective auger-electron therapy in an orthotopic glioblastoma xenograft model using convection-enhanced delivery. Theranostics 2016, Sep 29;6(12):2278-2291. (*Shared first and senior au-thorship). PMID: 27924163
S.S. Jensen, M. Meyer, S.A. Petterson, B. Halle, A.M. Rosager, C. Aaberg-Jessen, M. Thomas-sen, M. Burton, T.A. Kruse, B.W. Kristensen. Establishment and characterization of a tumor stem cell-based glioblastoma invasion model. PLoS One 2016, July 25;11(7). PMID: 27454178
S. Munthe, M.D. Sørensen, M. Thomassen, M. Burton, T.A. Kruse, J.D. Lathia, F.R. Poulsen, B.W. Kristensen. Migrating glioma cells express stem cell markers and give rise to new tu-mors upon xenografting. J Neurooncol. 2016, Oct;130(1):53-62. PMID: 27510953
B. Otvos, D.J. Silver, E.E. Mulkearns-Hubert, A.G. Alvarado, S.M. Turaga, M.D. Sørensen, P. Rayman, W.A. Flavahan, J.S. Hale, K. Stoltz, M. Sinyuk, Q. Wu, A. Jarrar, S.H. Kim, P.L. Fox, I. Nakano, J.N. Rich, R.M. Ransohoff, J. Finke, B.W. Kristensen, M.A. Vogelbaum, J.D. La-thia. Cancer stem cell-secreted macrophage migration inhibitory factor stimulates myeloid de-rived suppressor cell function and facilitates glioblastoma immune evasion. Stem Cells. 2016 Aug;34(8):2026-39. PMID: 27145382
B. Halle, M. Thomassen, R. Venkatesan, V. Kaimal, E.G. Marcusson, S. Munthe, M.D. Søren-sen, C. Aaberg-Jessen, S.S. Jensen, M. Meyer, T.A. Kruse, H. Christiansen, S. Schmidt, J. Mol-lenhauer, M.K. Schulz, C. Andersen, B.W. Kristensen. Shift of microRNA profile upon or-thothopic xenografting of glioblastoma spheroid cultures. J. Neurooncol 2016, July;128(3):395-404. PMID: 27063952
B. Halle, E. G. Marcusson, C. Aaberg-Jessen, S. S. Jensen, M. Meyer, M. K. Schulz, C. Andersen, Bjarne W. Kristensen, Convection-enhanced delivery of an anti-miR is safe and causes effi-cient target de-repression – a proof of concept, J Neurooncol. 2016 Jan;126(1):47-55. PMID: 26428358
D. L. Schonberg, T. E. Miller, Q. Wu, W. A. Flavahan, N. K. Das, J. S. Hale, C. G. Hubert, S. C. Mack, A. M. Jarrar, R. T. Karl, A. M. Rosager, A. M. Nixon, P. J. Tesar, P. Hamerlik, B. W. Kristensen, C. Horbinski, J.R. Connor, P. L. Fox, J. D. Lathia, J. N. Rich, Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells, Cancer Cell. 2015 Oct 12;28(4):441-55. PMID: 26461092
S. A. Petterson, R. H. Dahlrot, S. K. Hermansen, S. K. A. Munthe, M. T. Gundesen, H. Wohlle-ben, T. Rasmussen, C. P. Beier, S. Hansen and B. W. Kristensen. High levels of c-Met is associated with poor prognosis in glioblastoma, J Neurooncol. 2015 May;122(3):517-27. PMID: 25800004
J. D. Lathia M. Li, M. Sinyuk, A. G. Alvarado, W. A. Flavahan, K. Stoltz, A. M. Rosager, J. Hale, M. Hitomi, J. Gallagher, Q. Wu, J. Martin, J. G. Vidal, I. Nakano, R. H. Dahlrot, S. Hansen, R. E McLendon, A. E. Sloan, S. Bao, A. B. Hjelmeland, C. T. Carson, U. P. Naik, B. W. Kristen-sen, J. N. Rich. High-throughput flow cytometry screening reveals a role for junctional adhe-sion molecule A as a cancer stem cell maintenance factor. Cell Rep. 2014 Jan 16;6(1):117-29. PMID: 24373972
S. K. Hermansen, R. H. Dahlrot, Boye S. Nielsen, S. Hansen, B. W. Kristensen, MiR-21 ex-pression in the tumor cell compartment holds unfavorable prognostic value in gliomas. J Neu-rooncol. 2013 Jan;111(1):71-81. PMID: 23104517
Other outputs e.g. patents, novel therapies etc:
Our patent Auger electron therapy for glioblastoma (EP14173218.0) has led to establishment of the company – GlioPharma in 2015 – with the aim of setting up a clinical trial
Key collaborations:
Danish: Danish Cancer Society; OUH/SDU
International: Cleveland Clinic, USA; Henrich Heine University, Germany; DKFZ/Dept Neurol-ogy, University of Heidelberg, Germany; Linköping University Hospital, Sweden.
Infrastructure:
Stainings of tissue: automated equipment for staining, scanning of slides and image analysis
Molecular biology: sequencing equipment (Ion Torrent), equipment for genome-wide methylation profiling (Illumina)
Group leader: Bjarne Winther Kristensen
Group members: Total 12; 1 post doc (50%), 2 PhD students, 2 MSc students, 5 pregraduate MSc/MD students, 1 technician
Department & University/Hospital/Other:
Department of Pathology, OUH
Department of Clinical Research, SDU
Funding sources:
FSS, Novo Nordic Foundation, Danish Cancer Society, several private foundations
Description of research (please divide into main projects):
1) Influence of tumor microenvironment on therapeutic resistance
2) Inlfuence of tumor-brain interaction on tumor development and therapeutic resistance
3) Identification of novel biomarkers by experimental discovery stragegies combined with studies in clinical patient cohorts
4) Integreated brain tumor diagnostics with microscopy, next-generation sequencing and genome-wide methylation profiling.
Key publications (last 10 years):
S. Munthe, B. Halle, H.B. Boldt, H. Christiansen, S. Schmidt, V. Kaimal, J. Xu, S. Zabludoff, J. Mollenhauer, F.R. Poulsen, B.W. Kristensen. Shift of microRNA profile upon glioma cell mi-gration using patient-derived spheroids and serum-free conditions. J Neurooncol 2017, Jan 13, Epub ahead of print. PMID: 28091986
H. Thisgaard*, B. Halle*, C. Aaberg-Jessen, B.B. Olsen, A.S. Therkelsen, J.H. Dam, N. Langkjær, S. Munthe, K. Någren, P.F. Høilund-Carlsen*, B.W. Kristensen*. Highly effective auger-electron therapy in an orthotopic glioblastoma xenograft model using convection-enhanced delivery. Theranostics 2016, Sep 29;6(12):2278-2291. (*Shared first and senior au-thorship). PMID: 27924163
S.S. Jensen, M. Meyer, S.A. Petterson, B. Halle, A.M. Rosager, C. Aaberg-Jessen, M. Thomas-sen, M. Burton, T.A. Kruse, B.W. Kristensen. Establishment and characterization of a tumor stem cell-based glioblastoma invasion model. PLoS One 2016, July 25;11(7). PMID: 27454178
S. Munthe, M.D. Sørensen, M. Thomassen, M. Burton, T.A. Kruse, J.D. Lathia, F.R. Poulsen, B.W. Kristensen. Migrating glioma cells express stem cell markers and give rise to new tu-mors upon xenografting. J Neurooncol. 2016, Oct;130(1):53-62. PMID: 27510953
B. Otvos, D.J. Silver, E.E. Mulkearns-Hubert, A.G. Alvarado, S.M. Turaga, M.D. Sørensen, P. Rayman, W.A. Flavahan, J.S. Hale, K. Stoltz, M. Sinyuk, Q. Wu, A. Jarrar, S.H. Kim, P.L. Fox, I. Nakano, J.N. Rich, R.M. Ransohoff, J. Finke, B.W. Kristensen, M.A. Vogelbaum, J.D. La-thia. Cancer stem cell-secreted macrophage migration inhibitory factor stimulates myeloid de-rived suppressor cell function and facilitates glioblastoma immune evasion. Stem Cells. 2016 Aug;34(8):2026-39. PMID: 27145382
B. Halle, M. Thomassen, R. Venkatesan, V. Kaimal, E.G. Marcusson, S. Munthe, M.D. Søren-sen, C. Aaberg-Jessen, S.S. Jensen, M. Meyer, T.A. Kruse, H. Christiansen, S. Schmidt, J. Mol-lenhauer, M.K. Schulz, C. Andersen, B.W. Kristensen. Shift of microRNA profile upon or-thothopic xenografting of glioblastoma spheroid cultures. J. Neurooncol 2016, July;128(3):395-404. PMID: 27063952
B. Halle, E. G. Marcusson, C. Aaberg-Jessen, S. S. Jensen, M. Meyer, M. K. Schulz, C. Andersen, Bjarne W. Kristensen, Convection-enhanced delivery of an anti-miR is safe and causes effi-cient target de-repression – a proof of concept, J Neurooncol. 2016 Jan;126(1):47-55. PMID: 26428358
D. L. Schonberg, T. E. Miller, Q. Wu, W. A. Flavahan, N. K. Das, J. S. Hale, C. G. Hubert, S. C. Mack, A. M. Jarrar, R. T. Karl, A. M. Rosager, A. M. Nixon, P. J. Tesar, P. Hamerlik, B. W. Kristensen, C. Horbinski, J.R. Connor, P. L. Fox, J. D. Lathia, J. N. Rich, Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells, Cancer Cell. 2015 Oct 12;28(4):441-55. PMID: 26461092
S. A. Petterson, R. H. Dahlrot, S. K. Hermansen, S. K. A. Munthe, M. T. Gundesen, H. Wohlle-ben, T. Rasmussen, C. P. Beier, S. Hansen and B. W. Kristensen. High levels of c-Met is associated with poor prognosis in glioblastoma, J Neurooncol. 2015 May;122(3):517-27. PMID: 25800004
J. D. Lathia M. Li, M. Sinyuk, A. G. Alvarado, W. A. Flavahan, K. Stoltz, A. M. Rosager, J. Hale, M. Hitomi, J. Gallagher, Q. Wu, J. Martin, J. G. Vidal, I. Nakano, R. H. Dahlrot, S. Hansen, R. E McLendon, A. E. Sloan, S. Bao, A. B. Hjelmeland, C. T. Carson, U. P. Naik, B. W. Kristen-sen, J. N. Rich. High-throughput flow cytometry screening reveals a role for junctional adhe-sion molecule A as a cancer stem cell maintenance factor. Cell Rep. 2014 Jan 16;6(1):117-29. PMID: 24373972
S. K. Hermansen, R. H. Dahlrot, Boye S. Nielsen, S. Hansen, B. W. Kristensen, MiR-21 ex-pression in the tumor cell compartment holds unfavorable prognostic value in gliomas. J Neu-rooncol. 2013 Jan;111(1):71-81. PMID: 23104517
Other outputs e.g. patents, novel therapies etc:
Our patent Auger electron therapy for glioblastoma (EP14173218.0) has led to establishment of the company – GlioPharma in 2015 – with the aim of setting up a clinical trial
Key collaborations:
Danish: Danish Cancer Society; OUH/SDU
International: Cleveland Clinic, USA; Henrich Heine University, Germany; DKFZ/Dept Neurol-ogy, University of Heidelberg, Germany; Linköping University Hospital, Sweden.
Infrastructure:
Stainings of tissue: automated equipment for staining, scanning of slides and image analysis
Molecular biology: sequencing equipment (Ion Torrent), equipment for genome-wide methylation profiling (Illumina)