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Group Helena Carén

Research summary

Epigenetic processes control which genes that are expressed - in specific tissues and under specific conditions. Dysfunction of epigenetic control can lead to the development of diseases, including cancer. However, these changes are reversible and can potentially be “treated”. Recurrence of cancer is a major problem. A good initial response to treatment often occurs, whereas recurrent tumours are difficult to cure. Cancer stem cells are thought to be a driving force behind tumour recurrence.

In the group we are studying brain tumours, from children and adults. The most common type of adult brain tumour is glioblastoma. Glioblastomas are highly aggressive with a median survival of less than one year. In children, brain tumours constitute 1/3 of all cancers and are the leading cause of cancer-related mortality and morbidity. There are severe side-effects from the treatment and survivors often experience substantial long-term problems.

We use cancer stem cells from brain tumours and normal neural stem cells that we culture in vitro. The presence of cancer stem cells in brain tumours is well-established but knowledge on how to target them therapeutically is still missing. The long-term goals of our research are to increase survival of patients with brain tumours while decreasing adverse side-effects from treatments such as chemotherapy and radiotherapy. Short term goal is to improve the care of these patients by developing tools for improved diagnostics and prognostics. For this aim, we recently developed the epigenetic diagnostic classifier MethPed, which can aid in the diagnosis of these heterogeneous tumours that can be hard to diagnose accurately using standard techniques.

The group works very closely with many clinicians in Gothenburg; at the Neurosurgery department, the Oncology department and at the Children’s hospital.

Figure 1. (A) in vitro culturing of brain tumour cancer stem cells as adherent culture (top) or tumour spheres (bottom); (B) invasive properties of primary cancer stem cells (top) more closely resembling the primary tumours than classical cell lines (bottom); (C) treatment of the cells can induce alterations in key proteins (see Wenger et al, 2017). (D) MethPed bioinformatic classification of brain tumour subgroup with validation in patient material (for further information see Danielsson et al 2015).

Tools and Resources

We establish patient-derived in vitro cultures from patients undergoing surgery for brain tumours. We use a wide range of experimental and bioinformatic methods in the fields of cell biology, molecular biology and epigenetics.

Current group members

Helena Carén, PhD, Associate Professor
Anna Danielsson, PhD
Teresia Kling, PhD, Postdoc
Elin Möllerström, PhD, ‘forskar-AT’
Susanna Larsson, PhD student
Ágota Tűzesi, PhD student
Anna Wenger, research assistant
Sandra Ferreyra Vega, research assistant
Elizabeth Schepke, MD, PhD student
Katja Werlenius, MD, PhD student
Louise Carstam, MD, associated PhD student
Nidal Ghosheh, associated PhD student

Selected Publications

  1. Kling T, Wenger A, Beck S and Carén H. Validation of the MethylationEPIC BeadChip for fresh-frozen and formalin-fixed paraffin-embedded tumours. Clinical Epigenetics, 2017, 9:33
  2. Wenger A, Larsson S, Danielsson A, Juul Elbaek K, Kettunen P, Tisell M, Sabel M, Lannering M, Nordborg C, Schepke E and Carén H. Stem Cell Cultures derived from Pediatric Brain Tumors accurately model the originating tumors. Oncotarget. 2017. ‘Priority Research paper’
  3. Ahamed MT, Danielsson A, Nemes S and Carén H. MethPed: an R package for the identification of pediatric brain tumor subtypes. BMC Bioinformatics. 2016, 17:262
  4. Olsson M, Beck S, Kogner P, Martinsson T and Carén H. Genome-wide methylation profiling identifies novel methylated genes in neuroblastoma tumors. Epigenetics. 2016, Jan 19:0
  5. Danielsson A, Nemes S, Tisell M, Lannering B, Nordborg C, Sabel M and Carén H. MethPed: A DNA Methylation Classifier tool for the Identification of Pediatric Brain Tumor Subtypes. Clinical Epigenetics 2015, 7:62
  6. Carén H, Stricker SH, Bulstrode H, Gagrica S, Johnstone E, Bartlett TE, Feber A, Wilson G, Teschendorff A, Bertone P, Beck S and Pollard SM. Glioblastoma stem cells respond to differentiation cues but fail to undergo differentiation commitment and terminal cell cycle arrest. Stem Cell Reports 11/2015; 5:1-14.
  7. Carén H, Beck S and Pollard S. Differentiation therapy for glioblastoma – too many obstacles? Molecular & Cellular Oncology, 2015 Dec 28;3(2):e1124174
  8. Carén H, Pollard, Beck S. The Good, the Bad and the Ugly: Epigenetic mechanisms in glioblastoma, Molecular Aspect of Medicine. 2013, 34:849-862.
  9. Stricker S, Feber A, Engström P, Carén H, Kurian K, Takashima Y, Watts C, Dirks P, Bertone P, Smith A, Beck S and Pollard S. Widespread resetting of DNA methylation in glioblastoma-initiating cells suppresses malignant cellular behaviour in a lineage-dependent manner. Genes Dev. 2013 Mar 15;27(6):654-69.
  10. Djos A, Martinsson T, Kogner P and Carén H. The RASSF gene family members RASSF5, RASSF6 and RASSF7 show frequent DNA methylation in neuroblastoma. Molecular Cancer 2012, 11:40.
     

PubMed

 

 

 

Page Manager: Ulrika Lantz Carlsson|Last update: 4/13/2017
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