The National Cancer Institute recently awarded a five-year, $7.5 million program project grant to investigators at the Yale School of Medicine to continue studies on the role of viruses and mutant cellular proteins in tumorigenic transformation of cells.
This grant, "Program on the Molecular Basis of Viral and Cellular Transformation," is currently in its 31st year and is one of the largest and longest-running basic science grants at Yale. It coordinates studies to understand how viral genes and related cellular genes cause cells to escape normal growth controls and induce cancer.
"Because viruses are so well-defined and relatively simple compared to their host cells, we are optimistic that studies supported by this grant will continue to identify new targets for therapy and suggest new approaches to prevent and treat cancers," said principal investigator Daniel DiMaio, M.D., Waldemar Von Zedtwitz Professor of Genetics and vice chair of the Department of Genetics.
DiMaio studies human papillomaviruses (HPV), the causative agents of cervical cancer. His laboratory has shown that HPV oncogenes must be expressed continuously in cervical cancer cells for the cells to maintain their malignant characteristics, validating the viral genes as new therapeutic targets. In the current granting period, the DiMaio laboratory will continue to dissect the pathways activated when HPV oncogenes are repressed in cervical cancer cells.
Epstein-Barr Virus and Kaposi's Sarcoma Herpesvirus, two herpesviruses that are unusual in their ability to persist in patients in a latent state for many years, are 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, Sterling Professor of Molecular Biophysics and Biochemistry, also works on herpesviruses, focusing on the role of small viral RNAs in the induction and maintenance of tumors. Many RNAs that she studies were first identified in the collaboration with Miller supported by this grant.
Joann Sweasy, associate professor of Therapeutic Radiology and Genetics, investigates the role of mutant DNA polymerases in inducing cancer. Collaborating with DiMaio, she has found that some cancers may be due to inaccurate DNA synthesis by error-prone DNA polymerases.
"Working collaboratively on these related projects has enabled us to make much more rapid progress in understanding the molecular basis of cancer," said DiMaio.
Janet Rettig Emanuel