Brain Tumor Biology

Glioblastoma (GBM) is among the deadliest of solid tumors with median survival rates of approximately 12-15 months despite maximal therapeutic intervention. A rare population of self-renewing cells referred to as GBM cancer stem-like cells are believed to be the source of inevitable recurrence in GBM.

In our group, we have undertaken the challenging task to study GBM stem-like cells and their impact on therapeutic resistance in highly competitive and quickly evolving field of cancer research. The expertise in Brain Tumor Biology Team ranges from biochemistry, molecular, bio-imaging and cellular biology techniques to in vivo studies using avatars (patient-derived xenograft models).

Main research areas:

• Interrogation of molecular mechanism underpinning genomic instability and aberrant DNA repair in adult gliomas in the context of cellular hierarchies
• High-throughput drug screening with the aim to radio-sensitize pediatric diffuse midline gliomas
• Mass spectrometry and proteomic profiling of tissue and liquid biopsies of patients with CNS malignancies to identify novel prognostic biomarkers

Selected publications:

Pedersen H, Schmiegelow K, Hamerlik P: Radio-Resistance and DNA Repair in Pediatric Diffuse Midline Gliomas. Cancers 2020;12(10):2813

Obara EA, Morante DA, Rasmussen RD, Vitting-Serup K, Frias A, Elbæk KJ, Pedersen H, Lim YC, Jensen KE, Skjoth-Ramussen J, Brennum J, Tuckova L, Strauss R, Dinant C, Bartek J, Hamerlik P: SPT6-driven error-free DNA repair safeguards genomic stability of glioblastoma cancer stem-like cells. Nat Comm 2020;11(1):4709

Pedersen H, Obara EAA, Elbæk KJ, Vitting-Serup K, Hamerlik P: Replication Protein A (RPA) Mediates Radio-Resistance of Glioblastoma Cancer Stem-Like Cells. Int J Mol Sci 2020;21(5):1588

Michaelsen SR, Poulsen HS, Hamerlik P: VEGF-C as a putative therapeutic target in cancer. Oncotarget 2019;10(40):3988-3990

Zhang G, Dong Z, Prager BC, Kim LJ, Wu Q, Gimple RC, Wang X, Bao S, Hamerlik P§, Rich JN§. Chromatin remodeler HELLS maintains glioma stem cells through E2F3 and MYC. JCI Insight 2019;4(7):e126140

Michaelsen SR, Staberg M, Pedersen H, Jensen KE, Majewski W, Broholm H, Nedergaard MK, Meulengracht C, Urup T, Villingshøj M, Lukacova S, Skjøth-Rasmussen J, Brennum J, Kjær A, Lassen U, Stockhausen MT, Poulsen HS, Hamerlik P: VEGF-C sustains VEGFR2 activation under bevacizumab therapy and promotes glioblastoma maintenance. Neuro Oncol 2018; 20(11):1462-1474

Staberg M, Rasmussen RD, Michaelsen SR, Pedersen H, Jensen KE, Villingshøj M, Skjoth-Rasmussen J, Brennum J, Vitting-Seerup K, Poulsen HS, Hamerlik P: Targeting glioma stem-like cell survival and chemoresistance through inhibition of lysine-specific histone demethylase KDM2B. Mol Oncol 2018;12(3):406-420

Staberg M, Michaelsen SR, Rasmussen RD, Villingshøj M, Poulsen HS, Hamerlik P: Inhibition of histone deacetylases sensitizes glioblastoma cells to lomustine. Cell Oncol 2017;40(1):21-32

Rasmussen RD, Gajjar MK, Tuckova L, Jensen KE, Maya-Mendoza A, Holst CB, Møllgaard K, Rasmussen JS, Brennum J, Bartek J Jr, Syrucek M, Sedlakova E, Andersen KK, Frederiksen MH, Bartek J, Hamerlik P: BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity. Nat Commun 2016;7:13398

Rasmussen RD, Gajjar MK, Jensen KE, Hamerlik P: Enhanced efficacy of combined HDAC and PARP targeting in glioblastoma. Mol Oncol 2016;10(5):751-763