Hansen Lab

Group Leader

Lise Lotte Hansen
Associate Professor, PhD
More information  

RESEARCH
The main focus of our research is directed towards pathological changes in the epigenetic pattern and specific mutational status of cancer cells, aiming for a personalized approach for cancer treatment. We have developed methodologies for sensitive identification of genetic and epigenetic events behind different cancer diseases. Further characterization of such events has led to the development of biomarker assays for early cancer diagnostics, prognostics, and prediction of response to therapy.

Comprehensive whole genome screening of DNA methylation specific changes identified numerous new differentially methylated targets in breast cancer, which are being validated by locus specific highly sensitive methods, we have developed, in separate large patient cohorts. Highly specific biomarkers      are under development.

Epigenetic changes contributing to carcinogenesis and eventually leading to metastasis are mainly focused on DNA methylation and differential expression of specific microRNAs. The results are mutually correlated from inflamed lung tissue, nonmalignant lung tissue, primary lung tumors, and metastasis to the brain and lymph nodes. Differentially methylated DNA regions are mapped between osteosarcomas with and without the potential to form metastasis, with the aim to develop prognostic biomarkers for the disease.

In addition, we are exploring a possible correlation between hypoxia in the tumor and epigenetic changes. It is well known that some genes are down regulated during hypoxia and establishment of contributing epigenetic factors may provide new easily detectable biomarkers for hypoxia, which is needed in radiation therapy decision.

We have developed a highly sensitive mutation detection method, CADMA, targeting specific mutations influencing response to therapy in colon and lung cancer patients.

The environmental influence on changes in the epigenetic pattern is increasingly reported. In collaboration we have investigated environmental induced methylation changes in animal models. Further studies of several generations of mice are being prepared.

RESEARCH INTERESTS
Epigenetics and Cancer Genetics
Identification and development of new biomarkers for predisposition, early diagnosis, prognosis, and prediction of treatment outcome for cancer patients

Comprehensive genomic screening for epigenetic changes, validation of candidate genes, microRNAs, and other non-coding regions in different patient cohorts, to select highly specific biomarkers for clinical disease management

Development of new methodologies for robust and sensitive detection of DNA methylation based biomarkers

Non-invasive detection of DNA methylation specific biomarkers in body fluids (saliva, urine, blood/plasma (semi-invasive))

Investigate a potential correlation between epigenetic changes in chronic inflammations of lung tissue and carcinogenesis

Identify microRNAs, which are differentially expressed between nonmalignant lung tissue, lung tumor, and inflamed lung tissue.

Influence of hypoxic conditions on DNA methylation pattern

Implementation of new biomarkers and new methodologies for specific mutation detection in the clinic and in research

The environmental influence on changes of the DNA methylation pattern

Cancer types implemented in these studies: Breast cancer, Non-small Cell Lung Cancer, Malignant Mesothelioma, Colon cancer, Malignant Melanoma, Adrenal cancer, Osteosarcoma, Ovarian Cancer, Cervix Cancer.

Other tissue types: Inflamed lung tissue, liver tissue (mice)

Method development in our lab
Methylation Sensitive – High Resolution Melting (MS-HRM) to determine low levels of DNA methylation, was developed by T.K. Wojdacz in the lab. MS-HRM combines the HRM technology and an improved primer design addressing the PCR bias.  The method is characterized by state of art analytical sensitivity of methylation detection.

MS-HRM assays are being developed to detect differentially methylated sequences in body fluids as plasma, urine and sputum.

Sensitive Melting after real Time Methylation Specific PCR (SMART-MSP) was developed by L. S.  Kristensen. The method has an equal sensitivity to MS-HRM and was developed to avoid false positive results when determining DNA methylation status. The method led to the possibility of performing:

Allele-specific DNA methylation, which have the potential to be used in determining individual based cancer therapy.

Competitive Amplification of Differentially Melting Amplicons (CADMA) is a highly sensitive method to determine very low abundant mutations as somatic mutations in cancers. The method is being applied on known mutations in clinical samples.

METHODOLOGIES
DNA methylation detection: We have developed and patented methods for highly sensitive DNA methylation detection for single locus analysis:

Methylation Sensitive – High Resolution Melting (MS-HRM)  

Sensitive Melting after real Time Methylation Specific PCR (SMART-MSP)

Allele-specific DNA methylation detection

DNA methylation specific whole genome micro array analysis

DNA mutation detection:

We have developed Competitive Amplification of Differentially Melting Amplicons (CADMA) a highly sensitive method for mutation detection of known mutations

COLD-PCR

SNP- Genotyping

Multiplex Ligation Probe Amplification (MLPA) using self designed probes

Loss of Heterozygosity (LOH) mapping of cancer genomes

FISH, Fluorescence in situ Hybridization

Immunohistochemical methods

DNA sequencing: Bisulfite modified and Sanger sequencing

COLLABORATORS & Centers

  • Laboratory leader Jörg Tost, Development laboratory, Centre National de Génotypage (CNG), Evry, and Centre National de Génotypage (CEPH), Paris, France.
  • Chief Victor Lobanenkov and Dmitri Lukinov, Section of Molecular Pathology, NIAID-NIH, Rockville, MA, USA
  • Professor Jan Lubinski and International Hereditary Cancer Centre, Szczecin Poland
  • A/Professor Alexander Dobrovic, Molecular Pathology Research and Development Laboratory, Peter MacCallum Cancer Centre, Melbourne, Autralia
  • A/Professor Irene M. Pedersen, Dept. of Molecular Biology and Biochemistry, UCLA, Irvine, California.
  • Professor Bret Hassel, University of Maryland School of Medicine, Baltimore MD 21201, University of Maryland
  • A/Professor Emilia Wiechec, Intitute for Molecular and Clinical immunology, Magdeburg University, Germany.
  • Professor Jens Overgaard and Brita Singers, PhD, Dept. of Experimental Clinical Oncology, Aarhus University Hospital, Nørrebrogade, Aarhus, Denmark
  • Professor Torben F. Ørntoft, Department of Molecular Medicine, Aarhus University Hospital, Skejby, Denmark
  • Professor Stephen J. Hamilton Dutoit and
  • Pathologist Henrik Hager, Dept. of Pathology, Aarhus University Hospital, Nørrebrogade, Aarhus, Denmark
  • Professor Carsten Wiuf, Department of Mathematical Sciences, University of Copenhagen, DK-2100 Copenhagen Ø
  •  
  • Professor Ulla Vogel DTU, Hørsholm, DK
  • Professor Anders Lade Nielsen, Dept. of Biomedicine, Aarhus University
  • Assoc. Professor Claus Lindbjerg Andersen, Department of Molecular Medicine, Aarhus University Hospital
  • Assoc. Professor Lars Dyrskjøt, Department of Molecular Medicine, Aarhus University Hospital
  • Consultant Tine E Damsgaard, Dept. of Plastic Surgery Z, Aarhus University Hospital
  • Professor Jørgen Kjems, Dept. of Molecular Biology and Genetics, Aarhus University
  • Consultant Søren Cold, Dept of Oncology, Odense University Hospital, Odense

RESEARCH GROUP MEMBERS
Tomasz K. Wojdacz, PhD, postdoc; Helene Myrtue Nielsen, PhD student; Kristina Pedersen, PhD student (currently stationed in Baltimore, USA), PhD Gitte Brinch Andersen, PhD Tanni Borgbo, Iben L. Daugaard, PhD student; technician Tina Kjeldsen.

The group supervises research year students, Master and Molecular Medicine students, bachelor students, exchange MSc students.

                                

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Revised 03.08.2016