“I became interested in Wake Forest because of the diversity of the research the department offers.  The broad range of interests, coupled with collaboration within the department and with other departments provides students with numerous opportunities to expand their own interests.  The faculty's focus on training creates an atmosphere in which a student can truly grow as a researcher.”

Thesis Project

Adenovirus, a small DNA virus, has long been known to infect epithelial cells, resulting in respiratory infections and conjunctivitis.  Recent findings reveal that adenovirus infects most infants early in life. These findings have also highlighted the ability of adenovirus to establish a latent or persistent type infection in human lymphoid cells.  A productive adenovirus infection in lymphoid cells differs significantly from an infection in epithelial cells. First, the infection in lymphoid cells proceeds slowly, where maximal viral DNA synthesis is not reached until several days after infection.  The characteristic shut-down of host protein translation does not occur in adenovirus-infected lymphoid cells.  Strikingly, infected lymphocytes, unlike infected epithelial cells, continue to divide and replicate cellular DNA in the presence of adenovirus proteins that prevent the repair of double-stranded DNA breaks.  The wild-type virus suppresses cellular DNA-break repair by altering the location and quantity of several key cellular repair proteins. Consequently, the cellular repair machinery is unable to ligate the double stranded viral genome. However, signaling of double-stranded break damage still occurs via phosphorylation of Histone 2AX.  Therefore, infected lymphoid cells appear able to sense and signal DNA damage, but may be unable to repair DNA double-stranded breaks that arise spontaneously during cellular DNA replication.  The persistence of these DNA breaks may lead to repair by error-prone pathways or mechanisms that lead to genomic abnormalities such as chromosomal translocations and deletions.  The focus of this work is to determine the ability of adenovirus to prevent cellular DNA repair in lymphoid cells and measure the amount of DNA breaks and mutations occurring during infection.  These studies will provide insight into the relationship between lymphoid cells and adenovirus and will underscore mechanisms by which adenovirus infection could play a role in the etiology of leukemia in children.