Our lab has been conducting basic research on the pathobiology of the human papillomaviruses (HPVs) for over 25 years. These prevalent human pathogens establish persistent infections in epithelial tissues. Productive infections lead to warty lesion that may regress. Lesions recur during temporary or long term immunosuppression. Mucosotropic HPVs can be sexually transmitted and are of particular medical importance, as a low percentage of infections by oncogenic virus types, such as HPV-16 and HPV-18, can progress to high grade dysplasia and cancers, in particular, cervical, penile, anal laryngeal and tonsillar cancers. Our extensive examination of patient specimens has revealed that productive infection only occurs in differentiated squamous epithelia. Thus, virus production and genetic analyses to understand viral gene functions are best undertaken in squamous epithelia. Towards this goal, we have developed organotypic cultures of primary human keratinocytes, recapitulating a full thickness skin. Using this culture system we have examined the functions of virus encoded oncoproteins as well as the targeted host tumor suppressor proteins. We recently established a novel approach which produces for the first time high titers of infectious HPV-18 in this organotypic culture system. In the course of this work, we have gained many novel insights into virus-host interactions and revealed the molecular portrait of the productive infection in the squamous epithelium. We have also demonstrated the utility of this system for viral genetic analyses, not previous possible. The availability of infectious virus makes it possible to investigate infection process and mechanism of antibody neutralization of the virus. These studies will be important for developing inexpensive prophylactic vaccines. The lab has also conducted extensive functional analyses of the viral replication proteins and examined the mechanisms of viral DNA replication and persistence. This knowledge would facilitate drug discovery efforts to treat infections. The lab also uses a wide range of molecular and biochemical techniques, retrovirus-mediated gene transfer, and fluorescence imaging.
Dr. Chow received her PhD in 1973 in Chemistry from California Institute of Technology (Caltech) with Dr. Norman Davidson as her advisor. She investigated genome organization of bacterial phages and bacterium using the heteroduplex-electron microscopy method. 1973-74, post doctoral training, UC San Francisco and Caltech. 1975, Fellow, Cold Spring Harbor Laboratory; 1976 Staff investigator; 1977 senior staff investigator; 1979, senior scientist with tenure. At CSHL, she continued to use heteroduplex-electron microscopy to study phage and viral genome organization and regulation as well as cellular gene structure. Her work led to the first discovery that DNA inversion regulates gene expression in the phage Mu system (Kamp et al., 1978). She was the lead author for the work reporting the discovery of mRNA splicing in adenovirus (Chow et al.,1977). This work was awarded the Nobel Prize in Physiology or Medicine in 1993 to her collaborator R.J. Roberts and P.A. Sharp of MIT. 1984-93, associate professor and professor of Biochemistry at University of Rochester. 1993-current, UAB.