# Ceramide Signaling in the Regulation of Head & Neck Cancer Cell Death and Therapy

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $373,750

## Abstract

SUMMARY
Human papilloma virus (HPV) plays major roles in head and neck squamous cell carcinoma (HNSCC)
pathogenesis. Paradoxically, HPV(+) HNSCC patients respond better to chemotherapy, such as cisplatin
(CDDP), compared to HPV(-) HNSCC patients. However, molecular mechanisms and signaling pathways
involved in HPV-mediated chemosensitivity are largely unknown. Thus, the overall goal of this application is to
define the mechanisms involved in chemosensitivity of HNSCC cells in response to HPV infection with regard
to ceramide metabolism and signaling. Our therapeutic goal is to utilize this mechanistic information for the
development of novel strategies to enhance chemotherapy-induced HNSCC cell death and tumor suppression
without HPV infection. Based on our novel and unpublished preliminary data, we propose a novel hypothesis
that HPV16-E7 enhances CerS1/C18-ceramide-dependent lethal mitophagy in response to chemotherapy-
induced cellular stress signaling, leading to enhanced HNSCC cell death and tumor suppression. This
hypothesis will be tested in three Specific Aims: 1) Determine the roles of HPV16-E6 versus HPV16-E7 in the
regulation of ceramide-mediated lethal mitophagy; 2) Determine the mechanisms by which HPV16-E7
signaling enhances ceramide-dependent lethal mitophagy; and 3) Define the therapeutic roles and
mechanisms of HPV16-E7 signaling in the regulation of ceramide-dependent lethal mitophagy and HNSCC
tumor suppression. Overall, these studies will help develop mechanism-based therapeutic strategies to induce
HPV16-E7/C18-ceramide-mediated lethal mitophagy signaling for improving tumor suppression by
chemotherapy in HNSCC patients.

## Key facts

- **NIH application ID:** 9938513
- **Project number:** 5R01DE016572-15
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Besim Ogretmen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $373,750
- **Award type:** 5
- **Project period:** 2005-04-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938513

## Citation

> US National Institutes of Health, RePORTER application 9938513, Ceramide Signaling in the Regulation of Head & Neck Cancer Cell Death and Therapy (5R01DE016572-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9938513. Licensed CC0.

---

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