Metastasis: Molecular Studies and Methods Development

 

Our disease focus is on aspects of melanoma. We are currently centering on the transcription factor MITF, called by many as the master switch of the melanocyte, and its implication in melanoma, and also other critical melanoma-implicated signaling systems. We are also examining some of the cross-talk mechanisms between metastatic melanoma and normal surrounding tissue, using both animal and high throughput molecular techniques. We are also utilizing systems biology approaches, both for description of normal melanocyte function in the skin, and for modeling signalling systems and aspects of skin development.

Our group has competence on development and adaption of methodologies for molecular biology with particular relevance for cancer. These include, but are not limited to:

Gene therapy related technology, where we are trying to figure out a treatment combination to easily knock out any gene of interest in experimental systems. To do this, we have over the years been using antisense molecules, hammerhead ribozymes, peptide nucleic acids, and siRNA. In a string of papers, we have developed efficient protocols for photochemically induced gene modulation. In recent work, we have identified TAMRA as a photosensitizer, developed multifunctional PNA molecules,where one small molecule contains a fluorophor for both visualization and sensitization, a PNA antisense part, and a positively charged peptide part for endosomal entrapment. We are also working with biodegradeable molecules.

Genomics work, specifically microarray related techniques, including amplification and other ways around the problem of low amounts of sample material that is so common in for instance in a clinical cancer setting. We are also supporting the microarray project of the Norwegian Radium Hospital. We are also experimenting with high-resolution peptide-based kinase arrays and antibody cytokine arrays.


Mutation analyses work, where we previously have been developing methods including constant denaturant gel electrophoresis (CDGE), and cycling capillary gel electrophoresis (CCGE), compilation of TP53 and CDKN2A (p16) mutation databases (the latter (Cyclin-dependent kinase inhibitor A) is listed as the one in the HUGO Locus Specific Database), as well as having available a long range of assays for most clinically relevant cancer mutation. We have also published a string of papers on aspects of endogenous mutations in the human, including the contributions from the physical aspects of the human DNA sequence.

Bioinformatics, where we have pioneered network approaches in genomic applications, applied text mining for the biomedical literature, and participated in the development of the PubGene bioinformatics company. We have also calculated the human genome melting map, developed robust systems for statistical analysis of genomic data (The genomic hyperbrowser), to name some of our topics.

Translational work, where we try to take some of our gained insights closer to the clinic is also becoming more of a focus, with the advent of deep sequencing possibilities. in our recent case study, we show how knowing the detailed molecular changes in a tumor may have implications for cancer monitoring, and eventually offer potential treatment options.

If you would like to get in touch with us on these or related topics, please do not hesitate to do so!