Investigators

Summary

Studies on animal polyomaviruses have provided a wealth of information for cancer biology. Research on the simian and murine polyomaviruses (SV40 and PyV) led to the discovery of tumor suppressor proteins p53 and retinoblastoma (pRb) and unveiled the importance of tyrosine kinase activities in tumorigenic signaling. Our research exploits the human Merkel cell polyomavirus (MCV) that causes most Merkel cell carcinoma (MCC), a rare but deadly skin cancer that exhibits similarity to the tactile sensor “Merkel cells”. Despite the rarity of MCC, MCV infection is common, and nearly all healthy adults were asymptomatically infected and shed MCV from their skin. MCV is a small circular DNA virus that persists in currently unidentified dermal cells. There are two accidental events that are essential for MCV tumorigenesis and act as triggers that turn this common virus into a cancer-causing virus: insertion of linearized viral DNA into host cellular genome and introduction of a specific mutation that inactivates the viral replication enzyme.

By using molecular and cell biological approaches, our lab investigates: (1) MCV lifecycle processes, especially viral DNA replication, gene expression, and viral progeny production (2) MCV target cells wherein MCV persists or transforms into MCC, (3) biological triggers that disrupt the circular MCV DNA and facilitate insertion into host genome, and (4) critical cellular signaling activated by MCV proteins that promote MCC carcinogenesis. A full understanding of these events will help us prevent MCV-associated MCC, as well as identify therapeutic strategies for this deadly cancer.