Department of Biotechnology
Department of Biotechnology [DBT]
Understanding the genetic basis of cancer has been a significant thrust area in cancer biology after the discovery of DNA as the genetic material. However, most cancers are not hereditary and only 2% of our genome codes for genes. About half of the human genome is derived from transposons and their genetic remnants that are significant threats to its integrity. Retrotransposable elements are a class of transposons derived from ancient retroviral infections that have propagated in the human genome. Although most retrotransposons have lost their retrotransposition ability, a small fraction among them is still mobile. Retrotransposons pose a threat to genome integrity not only when they duplicate themselves but also by providing functional promoters and splice sites causing aberrant expression or structural changes to nearby genes. Mammalian genomes have evolved various mechanisms to curb the activity of retrotransposons; key among them is transcriptional silencing through epigenetic mechanisms including DNA methylation and heterochromatinization. Cancer cells however, exhibit widespread expression of retrotransposons along with a global loss of DNA methylation. Understanding how the epigenetic silencing mechanisms are lost and how derepressed retrotransposons alter the regulation and structure of nearby genes is key to understanding specific tumour properties such as chemoresistance. We are interested in deciphering which silencing mechanisms are lost in various human cancers with special focus on breast and pancreatic neuroendocrine cancers. In addition, we are interested in identifying the role of specific retrotransposons aberrantly expressed retrotransposons in breast and pancreatic tumorigenesis and whether they can be used to develop targeted immunotherapeutic approaches.
Current Research Grants
Ramalingaswami Fellowship Department of Biotechnology