# SLFN5: A Novel Therapeutic Target for Glioblastoma

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $345,625

## Abstract

PROJECT SUMMARY/ABSTRACT
Glioblastoma (GBM) is a highly aggressive malignancy with very high morbidity and mortality, due to lack of
effective therapies. The overall goal of this proposal is to identify novel cellular targets in GBM cells that could
lead to new therapeutic approaches. We have found that a member of the Schlafen (SLFN) gene family,
SLFN5, is significantly overexpressed in GBM as compared to normal brain, and that high levels of SLFN5
expression correlate with poor survival among GBM patients. Our data indicates that SLFN5 promotes GBM
growth by repressing IFN signaling and IFN stimulated gene (ISG) expression via an interaction with the
transcriptional activator STAT1. This highly novel finding forms the basis of the current proposal. Aim 1 will
identify elements of SLFN5-STAT1 complexes, define upstream regulatory signals required for the formation of
such complexes, and determine relationships between elements of these complexes and SLFN5-associated
transcriptional repression. The functions of different SLFN5 structural motifs and their importance to the
suppression of IFN-responses will be examined. Studies using primary samples from GBM patients will be
also employed for such studies. Aim 2 will define the effects of SLFN5 expression in vivo using three distinct
orthotopic engraftment models and GBM cell pairs with and without SLFN5 expression: i) conventional
xenograft models using athymic mice for examining the effects of SLFN5 on tumor establishment and growth;
ii) humanized orthotopic PDX models to examine SLFN5 effects for human-on-human immune response
against tumor, as well as to examine tumor response to immune checkpoint therapy; and iii) same a ii but
using mouse GBM syngeneic models in which the host animals have a fully functional immune system.
Altogether, the results of this work will provide important information on the mechanisms by which SLFN5
expression suppresses IFN-responses and promotes GBM growth. The successful performance of this work
should facilitate development of highly novel approaches for the treatment of GBM using SLFN5 as a target.

## Key facts

- **NIH application ID:** 10003400
- **Project number:** 5R01NS113352-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Charles David James
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $345,625
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003400

## Citation

> US National Institutes of Health, RePORTER application 10003400, SLFN5: A Novel Therapeutic Target for Glioblastoma (5R01NS113352-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10003400. Licensed CC0.

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