Epigenetics, Chromatin & Cancer
Since the completion of the human genome project, there is growing interest in heritable epigenetic information and its contribution to variation in the population, to normal cell function and to pathological conditions. At the molecular level, epigenetic inheritance and regulation of gene expression is often mediated through changes in DNA methylation patterns and changes in chromatin structure and composition.
Long term obgective: Our lab is studying the causes and consequences of epigenetic alteration in cancer. Aberrant silencing of tumor suppressor genes (TSG) is frequently observed in cancer cells and is thought to play important role in cancer initiation and progression. The cause of such silencing and the molecular mechanisms involved in establishment of the silent state are mostly not known and are at the center of research in the field. Several molecular mechanisms are known to contribute to maintenance of the silenced state. Understanding the relationships between the different components and the identification of additional players is of great interest and is expected to lead to development of novel therapeutic approaches aimed at reversing cancer associated epigenetic aberrations.
Experimental tools: Our experimental systems involve genetically engineered mouse cancer models as well as cultured human cells. We use genetic manipulation of cells or mice to establish assay systems for gene silencing or reactivation. Study of chromatin and DNA methylation and transcription is performed routinely in the lab using both locus specific methods and genomewide high throughput methods, followed by up-to-date computational analysis.