# Project 2-Three-dimensional modeling of EBV-HPV interactions leading to anogenital cell dysplasia

> **NIH NIH P20** · LSU HEALTH SCIENCES CENTER · 2020 · $207,944

## Abstract

ABSTRACT
Infections with high-risk sub-types of Human Papilloma Virus (HPV) are responsible for more than 99% of all
cervical carcinoma cases in the US. Our recent data in collaboration with Dr. Hagensee laboratory has shown
that co-detection of Epstein-Barr virus (EBV) with HPV in cervical samples increases the risk of concurrent
cervical dysplasia by 4-6 fold. In addition, HIV+ women from New Orleans (n=531) with detectable cervical
HPV and EBV are at higher risk (69%) for concurrent squamous intraepithelial lesions (SIL) as compared to
only 28% of women with only detectable HPV (p<0.001; OR 5.57, 95%CI 2.19-14.4). We hypothesize that EBV
acts as a co-factor for progression of HPV-related cervical cancers. We will address this hypothesis directly
using innovative 3-dimensional (3D) epithelial models of co-infection. First, using a well-characterized 3D
model of terminally differentiated keratinocytes, we will determine whether co-infection with HPV and EBV
adversely affects normal differentiation of the stratified multi-layer epithelium compared to HPV alone. Using
targeted molecular methods, we will dissect the augmenting capacity of EBV's oncoprotein, LMP-1, for cellular
transformation in the context of high-risk HPV types. Importantly, the proposed outcome measures will also
address epithelial transformation in the context of the low-risk HPV6 because HPV6 is found more frequently in
women shedding EBV, and since EBV's augmenting capacity might be greater in otherwise low-risk types.
Parallel experiments will be performed in primary and/or HPV-immortalized human ectocervical epithelial cells.
Utilizing expertise from all members of the COBRE team, the innovative 3D epithelial models utilized herein will
facilitate a powerful and direct investigation of whether co-infection with EBV enhances malignant
transformation. Specifically, these models allow for visualization of the stratified epithelial architecture and
invasion of the underlying stromal layer, quantification of basal cell proliferation, and several outcomes not
achievable with conventional 2D (monolayer) models. Also unique to the 3D model, we have the ability to
produce and utilize infectious HPV thus allowing for co-infection with live viruses rather than modeling HPV
infection by retroviral transduction of E6/E7 oncogenes. The mentoring duo of Drs. Alison Quayle and Augusto
Ochoa, combined with consulting provided by Drs. Michelle Ozbun and Hagensee, will provide excellent
scientific leadership to proposed COBRE mentee Dr. Chris McGowin. In line with the goals of the COBRE
mechanism, the combined track record of the proposed mentors for training of junior investigators will provide
Chris a rich environment conducive for translating his findings into independent R01 funding.

## Key facts

- **NIH application ID:** 9937785
- **Project number:** 5P20GM121288-04
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** Chris L McGowin
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $207,944
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9937785

## Citation

> US National Institutes of Health, RePORTER application 9937785, Project 2-Three-dimensional modeling of EBV-HPV interactions leading to anogenital cell dysplasia (5P20GM121288-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9937785. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*