# Targeting extracellular signaling-regulated kinase 5 (ERK5) in brain tumors and their microenvironment

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $367,548

## Abstract

Background: High-grade gliomas are among the leading cause of cancer-related death in children, with
diffuse intrinsic pontine glioma (DIPG) being a highly lethal subtype. DIPG commonly exhibits a mutation in
histone H3, referred to as H3K27M, which leads to gliomagenesis. However, the cell signaling events that
promote DIPG growth are not fully understood. We have discovered and recently shown that DIPGs are reliant
on extracellular signal-regulated kinase 5 (ERK5) for proliferation and survival. However, several critical
knowledge gaps of ERK5 function in DIPG remain. We will use an innovative syngeneic DIPG model in
combination with well-established models of DIPG to address several questions in this proposal. Specifically,
we hypothesize that ERK5 promotes growth through both glioma intrinsic effects and pro-glioma activities of
select glioma associated microglia and macrophages (GAMs). Significance: To support our preliminary data
and test our hypothesis we will study the role of ERK5 in three aims. Aim 1: Revealing functions of ERK5 in
GAMs and the importance of paracrine signaling with DIPG cells will provide valuable knowledge potentially
applicable to the development of new therapeutic modalities. Aim 2: Building a new paradigm by
understanding the dynamic characteristics of targeting multiple ERK pathways. Aim 3: ERK5 contains both a
transactivation domain and kinase domain unlike all other ERKs. Here we will delineate the functional role of
these domains and their contribution to glioma growth. Impact. This project leverages unique in vivo and in
vitro model systems to study a highly aggressive brain tumor. Our research will inform molecular mechanisms
and translational relevance of ERK5 in brain tumors, and be broadly applicable to other types of cancer and
neurosciences.

## Key facts

- **NIH application ID:** 10333364
- **Project number:** 5R01NS115831-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Sameer Agnihotri
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $367,548
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10333364

## Citation

> US National Institutes of Health, RePORTER application 10333364, Targeting extracellular signaling-regulated kinase 5 (ERK5) in brain tumors and their microenvironment (5R01NS115831-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10333364. Licensed CC0.

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