Dr. Hyun Jin Kwun’s research focuses on identifying the molecular mechanisms of viral oncogenesis in Merkel Cell Carcinoma (MCC), a rare but fatal form of skin cancer, with a nearly-tripled annual incidence in the last 20 years. Merkel cell polyomavirus (MCV), the only oncogenic human polyomavirus, is the cause for most MCC tumors. There are two relevant MCV viral oncoproteins: large T antigen (LT) and small T antigen (sT), which are implicated in oncogenesis through multiple mechanisms.

MCV LT phosphoprotein is required for MCV transcription, viral replication and cancer cell proliferation. MCV latency depends on controlling viral replication by initiating MCV LT turnover, via cellular Skp-Cullin-F box (SCF) ubiquitin complexes, reducing LT steady-state amounts to levels that prevent MCV replication. MCV sT is a main oncoprotein that plays a large role in the development of MCC. A unique domain of sT, known as the LT-stabilizing domain (LSD), previously identified by Dr. Kwun herself, has been reported to bind multiple E3-ubiquitin ligase complexes including FBW7 and beta-TrCP to increase and activate levels of cellular oncoproteins, such as c-myc and cyclin E. In addition, it also contributes to the viral transforming activity.

Currently, the primary focus in Dr. Kwun’s lab can be summarized in two sections:

• Investigating the roles of cellular kinase-E3 ubiquitin ligase networks in MCV replication and persistent infection.
• Investigating the mechanisms of sT-induced oncogenesis in MCC.