The National Cancer Institute recently awarded a five-year, $4.7 million program project grant to investigators at YaleSchool of Medicine to continue studies on the role of viruses in tumorigenic transformation of cells. Virus infection is thought to account for approximately 15% of all human cancers worldwide, and studies of tumor viruses have historically provided insight into basic cellular processes including carcinogenesis, cell cycle control, and signal transduction.
This grant, "Molecular Basis of Cancer Virus Replication, Transformation, and Innate Defense," is currently in its 41st year and is one of the largest and longest-running basic science grants at Yale. It coordinates studies to understand how viral genes allow cells to escape normal growth controls and induce cancer.
"Because viruses are relatively simple compared to their host cells, we are confident that studies supported by this grant will allow us to discover novel molecular mechanisms of carcinogenesis and possibly suggest new approaches to prevent and treat many cancers, not just those initiated by viruses," said principal investigator Daniel DiMaio, M.D., Ph.D., Waldemar Von Zedtwitz Professor of Genetics, Professor of Therapeutic Radiology, Professor of Molecular Biophysics and Biochemistry, and Deputy Director of the Yale Cancer Center.
DiMaio studies human papillomaviruses (HPV), the causative agents of several cancers including cervical cancer and a substantial fraction of head and neck cancers. In the current granting period, the DiMaio laboratory will explore the intracellular pathways HPV uses to enter cells.
Epstein-Barr Virus, which can persist in individuals in a latent state for many years, is the focus of George Miller, M.D., John Enders Professor of Pediatrics and Professor of Molecular Biophysics and Biochemistry and Epidemiology and Public Health. His laboratory is analyzing molecular events that maintain these viruses in the latent state, and the mechanisms for inducing these viruses to re-enter active growth.
Joan Steitz, Ph.D., Sterling Professor of Molecular Biophysics and Biochemistry, also works on herpesviruses, focusing on biochemical studies of the role of small viral RNAs in the induction and maintenance of tumors. Some of the RNAs that she studies were first identified in the collaboration with Miller supported by this grant.
Other important collaborators in these studies are Michael Krauthammer, Associate Professor of Pathology and director of the Bioinformatics Core of this Program; Akiko Iwasaki, Professor of Immunobiology; and Yong Xiong, Associate Professor of Molecular Biophysics and Biochemistry.