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MERIT Award Recipient: I. George Miller, M.D.

I. George Miller
Sponsoring NCI Division:Division of Cancer Biology (DCB)
Grant Number:R37CA12055
Award Approved:June 2003
Institution:Yale University
Department:Pediatrics
I. George Miller, M.D.
Literature Search in PubMed

Studies of Epstein-Barr Virus

Dr. Miller's research focuses on the biology of Epstein-Barr virus (EBV), the first recognized human cancer virus. EBV is etiologically associated with several human cancers including nasopharyngeal cancer, gastric cancer, Hodgkin's lymphoma, Burkitt's lymphoma and immunoblastic lymphoma. The experiments proposed in Dr. Miller's MERIT award grant address seminal unanswered questions about the behavior of an important human cancer virus and address a basic unresolved question in virology, "How do viruses switch from a latent to a lytic life style?"

In previous work, Dr. Miller identified several key viral genes which regulate the virus life cycle, including one gene, termed ZEBRA (Z E B Replication Activator), which mediates a switch between latency, a state in which only a few viral genes are expressed, and the lytic cycle, a phase when mature viruses replicate. This switch between latency and lytic replication is essential for the virus to spread from one cell to another, and from one individual to another.

This essential component of the viral life cycle is a potential target for development of anti-viral strategies. The MERIT grant poses two central questions: "What controls the expression of the gene encoding ZEBRA?" and "How does ZEBRA protein activate the cascade leading to lytic cycle expression of the virus?" The answers to these questions should provide new approaches to prevent and treat EBV-associated cancers.

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