Targeting Medulloblastoma by regulating RNA binding proteins

Email Principal Investigator
Ongoing
Specimen
Medulloblastoma
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Robert Schnepp

Winship Cancer Institute of Emory University
Atlanta, GA, USA
3

CBTN Participants

CBTN Pre-clinical Models Used

Backer

Institutional Funds

About this

Project

The Schnepp laboratory focuses on aggressive solid tumors including high-risk neuroblastoma, and rhabdomyosarcoma. Compared to adult tumors, these have few somatic mutations that can be targeted, suggesting the need to identify additional druggable targets. Previous work in the lab has identified the RNA-binding proteins (RBP) LIN28B and Musashi 2 (MSI2) as drivers of neuroblastoma proliferation, suggesting RBPs may be involved in other cancers as well . Prior studies have demonstrated a role for the RBP Mushashi1 (MSI1) in several pediatric brain tumors, including in medulloblastoma and glioma. High throughput RNAi and CRISPR based screening has identified several RBPs as crucial cancer dependencies in medulloblastoma cell lines. Among these ILF2 and LIN28B are relatively unexplored targets with known oncogenic function in the context of several other cancers. Based on this preliminary data we hypothesize that RBPs may play critical roles in meduloblastoma tumorigenesis and therefore a comprehensive elucidation of their roles will nominate additional direct and indirect targets for the treatment of these tumors and beyond.

Ask The

Scientists

Ask the scientists

What are the goals of this project?

To address this hypothesis we propose two specific aims. For our first aim we will delineate the functional consequences of two RNA binding proteins LIN28B and ILF2 in medulloblastoma. For our second aim we will employ a high throughput screening approach to globally assess the impact of RBPs on medulloblastoma cell proliferation and survival

What is the impact of this project?

Collectively, these studies are significant because patients with medulloblastoma are already treated to the cusp of therapeutic tolerability, mandating improved therapeutic approaches. This study provides a necessary foundation for designing possible new anti-RBP directed treatment approaches for patients with medulloblastoma. Moreover, given the diverse malignancies in which LIN28B, ILF2, and other RBPs are aberrantly expressed, our findings will likely generate new insights that extend to other pediatric tumors and beyond. They are innovative in their very conception as 1) the contribution of RBPs to pediatric tumorigenesis and 2) an unbiased, global evaluation of the role of all RBPs to tumor aggression have not been assessed.

Why the CBTN request is important to this project?

The Schnepp laboratory has experience in studying aggressive solid tumors including neuroblastoma and rhabdomyosarcoma but little experience in studying brain tumors like medulloblastoma. We currently have access to a few established medulloblastoma cell lines (D321, D556, DAOY) and a line derived from a patient treated here at Children’s Healthcare of Atlanta through the Ians Friends Foundation biorepository. We are reaching out to additional institutions including the CBTN to gain access to more medulloblastoma cell lines in order to demonstrate the RBP vulnerabilities in as many models as possible. By getting access to the medulloblastoma cell lines at CBTN we would be able to investigate the functional significance of targeting LIN28B, ILF2 and other RBPs in a broad range of medulloblastoma models.

Specimen Data

The Children's Brain Tumor Network will contribute to this project by providing cell lines.

Meet The

Team