Katzenellenbogen Lab

The research laboratory of Rachel Katzenellenbogen, MD is focused on human papillomavirus (HPV). HPV is a very common infection that affects more than 75 percent of the adult population. Nearly 5 percent of cancers worldwide are caused by HPV. Based on their association with cancer, different types of HPV are categorized as high-risk or low-risk.

The Katzenellenbogen Lab focuses on the host-pathogen interactions that activate oncogenic pathways and dysregulate typical cellular processes to permit cancer development and progression of HPV-associated cancers. The laboratory conducts fundamental molecular biology studies and works to link those models of disease to true pathophysiology in people.

Active Research

The Katzenellenbogen Lab is interested in understanding how the high-risk (HR) HPV viral oncogenes E6 and E7 drive cancer development and progression. Specifically, the laboratory studies the protein partnerships between HR E6 and cellular proteins that are co-opted from their typical role in cells.

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.

Studies in the laboratory have identified novel gene expression mechanisms used by HR E6 and NFX1-123, including RNA stabilization of the catalytic subunit of telomerase, known as hTERT, to drive its augmented expression.

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.

Research Funding

June 1, 2018—May 31,2020

NIH/NIAID

“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

NIH/NCI

“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

NIH/NCI

“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.

Recent Publications

For a full list of Dr. Katzenellenbogen’s publications, find her on PubMed.

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.

Faculty Research Team

Rachel A. Katzenellenbogen, MD

Rachel A. Katzenellenbogen, MD

Associate Professor of Pediatrics

Additional Research Team Members

Additional research team members in the Katzenellenbogen Lab are Kristin Robinson, research analyst and laboratory manager, and Justine Levan, graduate student.