# Intersections of RNA-binding proteins and T-cells in oral epithelial plasticity

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $454,933

## Abstract

ABSTRACT
RNA-binding proteins (RBPs) are critical regulators of gene expression in eukaryotes. However,
the contribution of RBPs in oral epithelial homeostasis and oral pathological diseases remain
mostly elusive. Our recent efforts demonstrate that dysregulated RBP HuR (Hu-Antigen R)
disintegrate oral epithelium and contribute to oral tumorigenesis. HuR can bind AU-rich elements
of mRNA sequences and regulates its stability of translation. Our preliminary data revealed that
HuR binds and controls the expression of a subset of mRNAs encoding proteins involved in
glucose metabolism. In collaboration with the Mehrotra group we show that epithelial specific HuR
cross talk with immune response and contribute to oral tumorigenesis. Using T-cell immune
plasticity functions, we plan to study the functional properties of HuR in oral epithelial and T-cells
for anti-tumor activity. Here, we demonstrated that epithelial-specific HuR knockout modulates
the epithelial homeostasis and oral tumorigenesis, whereas HuR KO T cells exhibit enhanced
IFNγ secretion by regulating glucose metabolism that alters the balance between the
immunosuppressive regulatory T cells (Treg's) and effector T cells. While the oral epithelial
alterations by HuR likely reflects the metabolic cues from T-cells, a major unanswered question
pertains to the mechanism of HuR in human oral cancer where there are immune suppression
and metabolic reprogramming. Collectively, HuR targets glucose metabolism genes in the oral
epithelium and its involvement in T-cell specific immune plasticity stimulated a coalescence of
efforts from the Palanisamy and Mehrotra groups to elucidate the underlying mechanisms of HuR
and oral tumorigenesis, and T-cell mediated immune plasticity, respectively. The overarching
hypothesis is that HuR-mediates gene regulation and cross-talk between oral epithelial and
immune T cells compartments by a novel mechanism, and silencing HuR associated gene
network is critical for epithelial and metabolic reprogramming to limit oral cancer progression. The
outcome of our studies will result in advanced therapeutic intervention studies and translation
from bench to bedside.

## Key facts

- **NIH application ID:** 10071277
- **Project number:** 1R01DE030013-01
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Shikhar Mehrotra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $454,933
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071277

## Citation

> US National Institutes of Health, RePORTER application 10071277, Intersections of RNA-binding proteins and T-cells in oral epithelial plasticity (1R01DE030013-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10071277. Licensed CC0.

---

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