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 corrected. 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, with an epigenetic focus. 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.

The presence of cancer stem cells in brain tumours is well-established but knowledge on what initiate and drives the tumours, and how to target them therapeutically is 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. For this we use cancer stem cell culture that we establish from tumour tissue from patients operated with brain tumours.

Short term goal is to improve the care of these patients by developing tools for improved diagnostics and prognostics. For this aim, we use and develop DNA methylation-based diagnostic classifiers.  We are currently running a national study to evaluate the benefit of using them in the clinical diagnostics of brain tumours in children.

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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- and molecular biology, pathology and genetics/epigenetics. 

Current group members

Helena Carén, PhD, Associate Professor
Maja Löfgren, PhD, Researcher
Teresia Kling, PhD, Researcher
Anna Wenger, PhD student
Sandra Ferreyra Vega, PhD student
Ida Carlsson, PhD student
Elizabeth Schepke, MD, PhD student
Katja Werlenius, MD, PhD student
Louise Carstam, MD, Associated PhD student
Olivia Näslund, MD, Associated PhD student

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

Recent selected publications

1. DNA methylation-based age estimation in pediatric healthy tissues and brain tumors.
   Kling T, Wenger A, Carén H. Aging (Albany NY). 2020 Nov 9;12. doi: 10.18632/aging.202145
    
2. Accumulation of DNA methylation alterations in paediatric glioma stem cells following fractionated dose irradiation.
   Danielsson A, Barreu K, Kling T, Tisell M and Carén H. Clin Epigenetics. 2020 Feb 11;12(1):26.
    
3. 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.
    
4. 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.
    
5. 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. 2018 Jan 27;20(1):25-31.
    
6. 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.
    
7. 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
    
8. 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’
    
9. 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
    
10. 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

More group Helena Carén publications on PubMed