Research SummaryElucidating the link between stemness and carcinogenesis- through the lens of an oncogenic virus
There is increasing evidence unvieling shared mechanisms between carcinogenesis and stemness. Cancer-causing (oncogenic) viruses are being implicated in the modulation of pluripotency as well. Viral oncoproteins target classic tumor suppressors (eg. pRB), increase cell proliferation and are now being found to transcriptionally regulate pathways traditionally associated with lineage commitment. Cancers caused by viruses serve as excellent models for the studying various aspects of cancer. Merkel cell polyomavirus (MCV) positive Merkel cell carcinoma (MCC) is one such unique new paradigm for human cancer, whereby a virus’ ability to modify/alter a cell can be used to understand the slow process of transformation leading to cancer. Using this MCV based model I propose to understand the complex relationship between stemness and cancer. I hypothesize that MCV oncoproteins reprogramme differentiated cells and that this is an important prerequisite of malignant transformation.
To test the hypothesis stated above, I want to investigate both the viral and the cellular angles to my model. Following are the key goals of the my proposed research:
- To examine MCV large T antigen’s (one of the viral oncoproteins) transcriptional regulation activity. (Viral perspective)
- To decipher why only Merkel cells develop this disease and investigate the cellular reprogramming capacity of MCV and its implications in cancer (Cellular perspective)