# Phase separation control of transcription in Ewing sarcoma

> **NIH CA R01** · UNIVERSITY OF ARIZONA · 2026 · $339,443

## Abstract

Phase separation control of transcription in Ewing sarcoma
 Eighty-five percent of Ewing sarcomas are caused by translocations between the
genes EWS and FLI1, creating a powerful oncogene – EWS-FLI1. The remainder are
caused by translocations involving an EWS homologue, FUS. This sarcoma is an
aggressive primary bone tumor affecting 1 in 300,000 people annually with more than 80%
of tumors occurring in adolescents, making it the second most common pediatric bone
cancer. Half of known translocations identified in sarcomas involve one of a family of three
proteins – FUS, EWS, and TAF15, known as the FET family of proteins. Our work over
the last few years has contributed to expanding the model for FET protein regulation of
transcription. FET proteins control transcription in an organizational capacity. FET proteins
undergo an assembly process called phase separation, which is the process thought to
drive formation of non-membrane bound organelles, also called granules.
 In this proposal, we highlight our accomplishments isolating an EWS-FLI1 associated
granule from cells. These granules have considerable similarity to those we have
discovered to associate with RNA polymerase II (RNA Pol II) during transcription, which
we refer to as transcription granules. This proposal aims to establish a model that EWS-
FLI1 fusion protein seed aberrant granules that incorporate EWSR1 and other FET
proteins to alter transcription and promote tumorigenesis. Our proposed work will
investigate basic molecular mechanisms by which EWS-FLI1 can contribute and drive
pediatric sarcoma pathology. Our proposal involves three aims. (1) We will determine the
binding partners that comprise fusion protein granules for EWS-FLI1. (2) We will
investigate EWS-FLI1 and EWSR1 activities to bind nucleic acids, phase separate, and
alter transcription through effects on nucleic structures. Finally, (3) we will investigate how
changes to DNA structure and chromatin are linked to aberrant phase separation b

## Key facts

- **NIH application ID:** 11239764
- **Project number:** 5R01CA259570-05
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Jacob C. Schwartz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** CA
- **Fiscal year:** 2026
- **Award amount:** $339,443
- **Award type:** 5
- **Project period:** 2021-12-16T00:00:00 → 2026-11-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11239764

## Citation

> US National Institutes of Health, RePORTER application 11239764, Phase separation control of transcription in Ewing sarcoma (5R01CA259570-05). Retrieved via AI Analytics 2026-05-18 from https://api.ai-analytics.org/grant/nih/11239764. Licensed CC0.

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