Chronic Virus Infections and Cancer
The Corcoran laboratory is interested in the complex interplay between chronic virus infection and cancer. Viruses that establish chronic infections are an undervalued yet significant feature of the human virome. Numerous, highly prevalent human viruses establish chronic infections that over time can trigger severe inflammatory disorders and cancer. Ten to fifteen percent of human cancers are caused by chronic virus infections. These include hepatitis B and C viruses, human papilloma viruses, and several members of the herpesviridae family, which after millions of years of co-evolution with humans are highly adept at reprogramming host immune responses and establishing life-long latent infection. Such complex virus-host interplay must be understood in molecular detail if we seek to intervene and treat these infectious cancers without causing harm. In addition, as has so often been the case in the past, understanding how viruses avoid normal intracellular checkpoints designed to prevent cancer and manipulate and subvert immune responses designed to target tumours provides a window into the complexities of cancer development and progression. Our model: Kaposi’s sarcoma (KS) is an unusual skin cancer caused by the virus, Kaposi’s sarcoma-associated herpesvirus (KSHV). KS lesions are characterized by proliferative endothelial cells and a highly inflammatory microenvironment. It is not known precisely how KHSV causes tumour formation, but the emerging model is that different viral gene products work together to elicit the phenotypes associated with KS, including inflammation. In my lab, we want to identify and understand how different KSHV proteins contribute to the early stages of cancer by reprogramming normal endothelial cell function.