# Understanding the Roles of the E6 and E7 Oncoproteins in MmuPV1 Induced Carcinogenesis

> **NIH NIH F32** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $64,926

## Abstract

Project Summary/Abstract
Human papillomavirus (HPV) causes approximately 5% of all human cancers. While HPV's transforming and
tumorigenic properties have been studied extensively in vitro using tissue culture models and in vivo using
transgenic animal models that express the HPV oncoproteins, the relevance of these functions in HPV-induced
disease have not been verified in a true physiological model. A barrier to understanding HPV oncoprotein function
is that HPV cannot infect murine cells, which disallows one from studying HPV disease in laboratory mice. The
recent discovery of murine papillomavirus (MmuPV1) provides us the opportunity to study in a preclinical model
natural infections and the ability of papillomaviruses to promote neoplastic disease through their oncoproteins,
specifically E6 and E7. Using MmuPV1, we have established a mouse model for HPV-induced neoplastic
disease in mice allowing us to now define the roles of the E6 and E7 oncoproteins in the context of natural
papillomavirus infection. MmuPV1 infects both cutaneous and mucosal epithelia, the later mimicking neoplastic
disease caused by the “high-risk” α-HPVs. The latter finding is interesting because MmuPV1 E6 and E7
oncoproteins biochemically mimic the β- and γ-HPVs. We will examine the functions of the MmuPV1 E6 and E7
oncoprotein's in promoting MmuPV1-induced disease, specifically E6's ability to inhibit NOTCH signaling and
E7's effects on non-canonical RB function. Using genetically engineered mouse models (GEMMs), we will
rigorously test the importance of these functions in promoting skin carcinogenesis using cellular mutations that
may complement for these specific functions of E6 and E7. Finally, we will determine if the E6 and E7
oncoproteins from the “high-risk” α-HPV, HPV16, can trans-complement for MmuPV1 E6 and E7 oncoproteins
using our existing HPV16 transgenic animal models. These studies will further our understanding of the roles E6
and E7 play in promoting papillomavirus-induced disease and could be used to develop novel therapies that
target these functions.
The main goal of this postdoctoral fellowship is to help me develop the skill sets needed to become a successful
faculty member at a research-focused academic institution. The proposed training plan provides me with a
unique set of means by which to accomplish this goal including a strong mentoring plan, many opportunities to
develop my skills as a mentor and teacher, and an array of career development opportunities including one
focused specifically on helping under represented minorities be successful in academia as professors. This
combined with the strong training record of my sponsor, Dr. Paul Lambert, and my strong record of productivity
as a graduate student are compelling reasons why I should be successful in attaining my career goals. By
accomplishing the research goals and training plan, I hope to establish an important niche in the papillomavirus
field and to develop the skill sets necessary...

## Key facts

- **NIH application ID:** 10067803
- **Project number:** 1F32CA254019-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** James Romero-Masters
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,926
- **Award type:** 1
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10067803

## Citation

> US National Institutes of Health, RePORTER application 10067803, Understanding the Roles of the E6 and E7 Oncoproteins in MmuPV1 Induced Carcinogenesis (1F32CA254019-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10067803. Licensed CC0.

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