Epigenetic regulation in cancer
Better understanding of the underlying biological mechanisms leading to cancer development is crucial for improved therapy in the future. Healthy tissue identity is caused by epigenetic regulation, and cancer cells can be viewed as cells that have lost tissue identity; thus, understanding epigenetic dysregulation may lead to new and important understanding of cancer development.
In breast cancer, we have developed a bioinformatic approach (termed emQTL) for identification of epigenetically regulated pathways, incorporating genome-wide DNA methylation and gene expression data as well as functional epigenetic profiling and transcription factor binding data . In this work we showed that loss of enhancer methylation allowed transcription factor binding activity and increased signaling that lead to increased proliferation in a subgroup of breast cancer. This approach has not yet been applied to other cancers, and may provide new insight into epigenetic regulation across multiple cancer types.
The overarching aims of the project is to identify and characterize epigenetically regulated pathways in one or more cancer types including lung cancer, prostate cancer, pancreatic cancer and others. This work will result in increased knowledge of cancer development, and identification of new subgroups of cancer. This aim will be achieved using an improved approach based on Fleischer, Tekpli et al .
Specific objectives are to 1) run a pilot analysis for several cancer types to assess which cancers have epigenetic regulation of cancer-associated pathways, to 2) characterize in detail epigenetically regulated pathways in one cancer type, and 3) identify new patient subgroups in this cancer type. Finally, 4) genomic candidates for epigenetic regulation may be functionally assessed in cell lines.
The student will learn bioinformatics, primarily programming in R, allowing the student to analyze and interpret any large scale ‘omics data (genomics, transcriptomics, epigenomics etc.). No prior knowledge of R programming is required, but a strong desire to learn is mandatory. The student will get a broad and comprehensive understanding of cancer biology and treatment of cancer, and will also learn wet-lab techniques such as DNA and RNA isolation, quantitative PCR and pyrosequencing.
The master project will take place at the Radium Hospital, Department of Cancer Genetics, Project group Epigenomics of Breast Cancer. The Radium Hospital is a world leading multidisciplinary environment for cancer research where cutting edge medical research is conducted, and the student will have the opportunity to attend frequent scientific presentations. The project group includes four members working with epigenetic regulation in breast cancer, and we are part of a bigger group working on computational systems medicine.
1. Fleischer, T., et al., DNA methylation at enhancers identifies distinct breast cancer lineages. Nat Commun, 2017. 8(1): p. 1379.