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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 have 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. We are currently running a national study to evaluate the benefit of using it in clinical diagnostics.

The group works very closely with many clinicians in Gothenburg; at the departments of Neurosurgery, Oncology and Pathology 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.

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
Maja Löfgren, PhD
Teresia Kling, PhD, Postdoc
Anna Wenger, PhD student
Sandra Ferreyra Vega, PhD student
Elizabeth Schepke, MD, PhD student
Katja Werlenius, MD, PhD student
Pavle Pazanin, Statistician
Josephine Kalm, Biomedical Scientist
Agnes Torell Björkman, Research Assistant
Louise Carstam, MD, Associated PhD student
 

Recent selected publications

  1. Intra-Tumor DNA Methylation Heterogeneity in Glioblastoma; Implications for DNA Methylation-Based Classification.
    Wenger A, Ferreyra Vega A, Kling T, Olsson Bontell T, Jakola AS and Carén H. Neuro Oncol. 2019, Jan 22. doi: 10.1093/neuonc/noz011.
     
  2. Cell line-based xenograft mouse model of paediatric glioma stem cells mirrors the clinical course of the patient.
    Larsson S, Wenger A, Dosa S, Sabel M, Kling T and Carén H. Carcinogenesis. 2018, Jun 30.
     
  3. Determinants for Effective ALECSAT Immunotherapy Treatment on Autologous Patient-Derived Glioblastoma Stem Cells.
    Wenger A, Werlenius K, Hallner A, Berg-Thorén F, Farahmand D, Tisell, Smits A, Rydenhag B, Jakola A, Carén H. Neoplasia. 2017 Nov 27;20(1):25-31.
     
  4. Pediatric brain tumor cells release exosomes with a miRNA repertoire that differs from exosomes secreted by normal cells. 
    Tuzesi A, Kling T, Wenger A, Lunavat TR, Jang SC, Rydenhag B, Jötvall J, Pollard SM, Danielsson A and Carén H. Oncotarget, 2017 Oct 6;8(52):90164-90175.
     
  5. Validation of the MethylationEPIC BeadChip for fresh-frozen and formalin-fixed paraffin-embedded tumours. 
    Kling T, Wenger A, Beck S and Carén H. Clinical Epigenetics, 2017, 9:33
     
  6. Stem Cell Cultures derived from Pediatric Brain Tumors accurately model the originating tumors. 
    Wenger A, Larsson S, Danielsson A, Juul Elbaek K, Kettunen P, Tisell M, Sabel M, Lannering M, Nordborg C, Schepke E and Carén H. Oncotarget. 2017, 8(12):18626-18639. ‘Priority Research paper’
     
  7. MethPed: an R package for the identification of pediatric brain tumor subtypes. 
    Ahamed MT, Danielsson A, Nemes S and Carén H. BMC Bioinformatics. 2016, 17:262
     
  8. Genome-wide methylation profiling identifies novel methylated genes in neuroblastoma tumors.
    Olsson M, Beck S, Kogner P, Martinsson T and Carén H. Epigenetics. 2016, Jan 19:0
     
  9. MethPed: A DNA Methylation Classifier tool for the Identification of Pediatric Brain Tumor Subtypes.
    Danielsson A, Nemes S, Tisell M, Lannering B, Nordborg C, Sabel M and Carén H. Clinical Epigenetics. 2015, 7:62
     
  10. Glioblastoma stem cells respond to differentiation cues but fail to undergo differentiation commitment and terminal cell cycle arrest.
    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. Stem Cell Reports. 11/2015; 5:1-14.
     

 

More group Helena Carén publications on PubMed

Contact information

Helena Carén

E-mail: Helena Carén
Phone: +46 (0)31 786 3838

Visiting address:
Sahlgrenska Cancer Center
Medicinaregatan 1F
413 90 Gothenburg

Page Manager: Yael Zukovsky Fitoussi|Last update: 10/9/2019
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