Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Shenk, Thomas E.
Location Princeton University
Primary Field Microbial Biology
Secondary Field Cellular and Developmental Biology
 Election Citation
Shenk pioneered the technology to create and utilize mutations in genes and oncogenes of the DNA tumor viruses, adenoviruses, and SV40. He described the transcriptional signals, RNA processing sites (polyandenylation), RNA transport factors, and translational controls mediated by these viruses. He elucidated the functions of the adenovirus oncogenes.
 Research Interests
My laboratory studies the biology of adenovirus and cytomegalovirus. Both of these viruses are widespread in the human population. Adenoviruses generally do not cause serious disease in humans, but they induce tumors in susceptible rodents and transform cultured rodent cells to an oncogenic phenotype, providing a model system for the study of oncogenesis. Human cytomegalovirus can cause life-threatening disease in immunocompromised individuals, including transplant recipients and AIDS patients. In both of these systems, we explore viral gene functions, initially by analyzing the consequences of specific mutations in the viral genome and subsequently by exploring the biochemical functions of viral proteins. Recently, we have determined that the adenovirus E4orf6 protein binds to the cellular tumor suppressor p53. This interaction interferes with the normal transcriptional activation function of p53 and endows the E4 protein with oncogenic potential. We have also demonstrated that two cytomegalovirus immediate early proteins, IE1 and IE2, can block apoptosis. Apoptosis, or programmed cell death, has many biological functions, including a role in the defense against some viral infections. When the infected cell dies rapidly, viral replication and spread is inhibited in an infected organism. The IE1 and IE2 proteins block the host apoptotic defense, enabling the virus to complete its replication cycle.

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