# Targeting SS18-SSX biology in synovial sarcomagenesis

> **NIH NIH U54** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $499,990

## Abstract

Overall: PROJECT SUMMARY/ABSTRACT (Parent Award)
This application responds to RFA-CA-17-049 by proposing the establishment of a center distributed across
three institutions with labs all focusing on the biology of the SS18-SSX (formerly called SYT-SSX) fusion
oncogene. Among the FusOnC2 consortium cancers of interest, synovial sarcoma has the highest incidence in
the United States and worldwide, but has been a specifically underserved malignancy due to its predilection for
the adolescent and young adult population and its relatively poor responsiveness to systemic therapy,
compared to other pediatric sarcomas that also associate with fusion oncogenes. While much of the biology of
SS18-SSX remains unknown and synovial sarcoma patients represent a clearly underserved, orphan-disease
population, there are two principles at the extremes of the cancer biology spectrum that are well established.
First, SS18-SSX has proven the capacity to recapitulate synovial sarcomagenesis faithfully in the mouse
without the need of introduced or stochastically acquired secondary genetic changes, second SS18-SSX has
biochemically demonstrated interactions with an important chromatin remodeling complex called SWI/SNF or
BAF. This application proposes to build three research projects focused on the cell biology of transformation,
genome-wide chromatin biology and SWI/SNF (BAF) complex componentry biology, each related to SS18-
SSX. These discovery biology and therapeutic target identification efforts will be supported by two shared
resource cores that will provide human validation of therapeutic targets and preclinical testing of therapeutic
strategies. The group of investigators has developed as an organically assembled network of collaborations,
built over the last decade, during which time each project has gathered substantial preliminary data using a
variety of functional screens, a newly identified cell of origin, the ability to track SS18-SSX genome wide
localization and protein interactions, a powerful system to produce and evaluate recombinant SWI/SNF (BAF)
complexes with variable componentry, and powerful mouse genetic models of synovial sarcoma—including
spontaneous development of metastatic disease. Preliminary data are sufficiently robust to recommend
therapeutic strategies immediately from each research project for the cores to validate and evaluate in clinically
relevant mouse models and quantitative molecular imaging.

## Key facts

- **NIH application ID:** 10657265
- **Project number:** 3U54CA231652-01S1
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Kevin Bruce Jones
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $499,990
- **Award type:** 3
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10657265

## Citation

> US National Institutes of Health, RePORTER application 10657265, Targeting SS18-SSX biology in synovial sarcomagenesis (3U54CA231652-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10657265. Licensed CC0.

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