The laboratory has identified that the protein partnership of HR E6 and the cellular protein NFX1-123 is fundamental to the upregulation of telomerase—a required enzyme for cellular immortalization and universally activated in HPV-associated cancers—and to Notch1, a master cell fate regulator.
The Katzenellenbogen Lab leverages normal and HPV-associated patient cancer samples to link the basic molecular pathology and mechanistic work studied in the laboratory to true clinical disease. The laboratory recognizes understanding the basic biology of an HR HPV infection in a host cell is fundamental in demonstrating ways to identify, treat, and eliminate the morbidity and mortality associated with HR HPV infections.
June 1, 2018—May 31,2020
“Cellular RNA binding and regulation by NFX1-123 and its perturbation by high-risk human papillomavirus E6”
The goals of this project are to investigate the hijacking of a host cell RNA binding protein by HPV E6 to drive dysregulation in HPV infections and cancer development.
September 1, 2016—August 31, 2021
“HIV integration-mediated modulation of immune regulation in HPV-associated cancers”
The major goals of this project are to determine whether HIV infection drives a novel mechanism for HPV-associated cancer development and progression.
June 4, 2014—May 31, 2019
“HPV E6 and NFX1-123 in differentiation, cell regulation and cancer”
The major goals of this project are to understand the collaborative role of NFX1-123 and HPV E6 in gene regulation, in epithelial architecture, and in cancer development and progression.
PA Vliet-Gregg, JR Hamilton and RA Katzenellenbogen. NFX1-123 and human papillomavirus 16E6 increase Notch expression in keratinocytes. J Virol 2013;87(24):13741-13750. PMID24109236. PMC3838236.
M Xu, RA Katzenellenbogen, C Grandori and DA Galloway. An unbiased in vivo screen reveals multiple transcription factors that control HPV E6-regulated hTERT in keratinocytes. Virology 2013;446(1-2):17-24. PMID24074563. PMC3787310.
RA Katzenellenbogen, JJ Carter, JE Stern, MS Butsch Kovacic, PA Mehta, SL Sauter, DA Galloway and RL Winer. Skin and mucosal human papillomavirus seroprevalence in persons with Fanconi Anemia. Clin Vaccine Immunol 2015;22(4):413-420. PMID25651924. PMC4375352.
PA Vliet-Gregg, JR Hamilton and RA Katzenellenbogen. Human papillomavirus 16E6 and NFX1-123 potentiate Notch signaling and differentiation without activating cellular arrest. Virology 2015;478:50-60. PMID25723053. PMC4383269.
RL Winer, CE Huang, S Cherne, JE Stern, MS Butsch Kovacic, PA Mehta, SL Sauter, DA Galloway and RA Katzenellenbogen. Detection of human papillomavirus in the oral cavities of persons with Fanconi anemia. Oral Dis 2015;21(3):349-354. PMID25158861. PMC4344428.
J Levan, P Vliet-Gregg, K Robinson, and RA Katzenellenbogen. Human papillomavirus type 16 E6 and NFX1-123 mislocalize immune signaling proteins and downregulate immune gene expression in keratinocytes. PLoS One 2017; 12(11):e0187514. PMID29117186. PMC5695606.
Additional Research Team Members
Additional research team members in the Katzenellenbogen Lab are Patty Gonzalez-DeWhitt, research analyst and laboratory manager, and Kevin Quist, research technician.