Welcome to the Katzenellenbogen Lab
In the Katzenellenbogen lab, we are studying Human Papillomavirus (HPV). HPV is the most common sexually transmitted infection, affecting more than 75% of the adult population. HPV is categorized as high-risk or low-risk, based on its association with cancer. Through dysregulation of normal cellular function, high-risk HPV blocks signals for DNA damage, programmed cell death and cellular arrest, all as a part of its viral life cycle. I am studying the mechanism by which high-risk HPV activates telomerase, an enzyme found normally in stem cells and is almost categorically activated in cancers, in order to understand how HPV drives cells to become malignant.
Current Research Projects
We are studying how the E6 oncoprotein of high-risk HPV 16 affects telomerase activity in cells, and specifically the catalytic subunit of telomerase, hTERT. HPV 16E6 can increase telomerase expression through transcriptional activation of hTERT, but we have found that HPV 16E6 also increases hTERT post-transcriptionally through its interaction with NFX1-123. NFX1-123 is an endogenous protein, found in the cytoplasm of epithelial cells, and this protein can bind to and increase the stability of the hTERT mRNA. We are working to determine the way in which NFX1-123 binds to and affects hTERT mRNA, why it is required for full telomerase activity in HPV 16E6 expressing cells and what other RNAs are regulated by NFX1-123.
We also are studying the role of NFX1-123, HPV 16E6 and other RNA processing proteins in cervical cancer, tumorigenesis and the tumor virus life cycle.
We hope to better understand how high-risk HPV infections lead to cancer, use HPV as a model of oncogenic progression and use HPV as a model for the life cycles of other DNA tumor viruses.
Dr. Katzenellenbogen is an assistant professor in the Department of Pediatrics, Division of Adolescent Medicine at the University of Washington. She is a member of the Center for Childhood Infections and Prematurity Research at Seattle Children's Research Institute, where her laboratory is physically located. She is also a member of the Pediatric Infectious Disease training program and the Adolescent Medicine training program, and is an affiliate of the Fred Hutchinson Cancer Research Center and the Center for AIDS and STD. She is an emerging expert on the role of post-transcriptional regulation of hTERT; funding for her research is in part supported by the NCI-NIH.