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

About the PNAS Member Editor
Name Chow, Louise T.
Location University of Alabama at Birmingham
Primary Field Genetics
Secondary Field Biochemistry
 Election Citation
Using electron microscopy, Chow and collaborators discovered mRNA splicing. Chow discovered alternative RNA splicing, and alternative promoter and polyadenylation utilization. Chow is also a pioneer in human papillomavirus biology, including achieving productive infection in epithelial tissue culture, thereby paving the way for further genetic analysis and antiviral drug discovery.
 Research Interests
The lab established the first experimental model system which produces robust infectious HPV-18 in differentiating organotypic raft cultures of primary human keratinocytes cultured at the liquid medium/air interface. Raft cultures of PHKs transduced with HPV E6, E7 oncogenes and of cervical cancer cell lines simulate dysplasias or cancers, respectively. Using these cultures, the lab has identified pathways, in particular the DNA damage response, which HPV activates to support viral DNA amplification and viral pathogenesis. Rationally selected pathway-specific inhibitors effectively stop productive infection and cancer cell growth. The lab also characterizes inhibitory effects of compounds supplied by biotech companies. Dr. N. Sanjib Banerjee in the lab additionally established organoid raft cultures (ORCs) or xenografts of primary cervical cancer (PDXs) in SCID mice. ORCs can also be used to initiate PDXs or 3-dimensional organoids in multi-well plates. These reciprocal and complementary in vitro and in vivo systems are used to evaluate and repurpose inhibitors as therapeutic candidates to treat HPV-cancers. Together with long-time collaborator Dr. Zhi-Ming Zheng of NCI, her lab has helped characterize altered expression of host protein-coding genes and noncoding miRNAs and lnc RNAs across the stages of carcinogenesis. These changes potentially serve as biomarkers for viral carcinogenesis.

 
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