Investigators

Summary

The work of our group (jointly directed by Patrick Moore and Yuan Chang) has focused on human tumor viruses since the early 1990s when we identified Kaposi's sarcoma associated herpesvirus (KSHV/HHV8) and showed that this virus was causally associated with Kaposi's sarcoma, the most common AIDS-related cancer in the United States and the most common malignancy in parts of Africa. We sequenced the KSHV genome, developed serologic assays, determined its prevalence in human populations, and characterized many of its critical viral oncoproteins. We have continued to study virus-host cell interactions in the context of dysregulation of pro-proliferative and anti-apoptotic pathways. We recently identified the seventh human tumor virus, Merkel cell polyomavirus (MCV), from a Merkel cell carcinoma (MCC). We characterized the transcriptional products of MCV and described the early region viral T antigen oncoproteins. Our work has established that MCV causes ~80% of MCC: we determined that the virus is clonally integrated in MCC tumor cells; that human tumor-associated Large T (LT) antigens contain signature truncation mutations; that T antigen proteins are expressed in MCC tumor cells by novel antibodies we developed; and we are the first laboratory to show rodent cell transformation by MCV sT antigen but not the LT antigen. We have identified several novel cellular interactors for MCV T antigens that open new avenues of investigating critical oncogenic signaling pathways. We have focused on many aspects of cancer etiology as modeled through oncogenic tumor viruses.