# Discovery and characterization of exceptionally specific surface oncoprotein LIPI in Ewing Sarcoma

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2024 · $216,512

## Abstract

Project Summary
Children and young adults with metastatic Ewing sarcoma driven by oncogenic fusion transcription factor EWS-
FLI1 continue to have poor outcomes. Immunotherapies using T cells, NK cells, cancer vaccines, and
monoclonal antibodies are being considered for Ewing sarcoma, especially for recurrent patients. The
identification of human tumor-associated antigens (TAAs) recognized by the immune system is crucial for
immunotherapy. Through integration of Ewing sarcoma cell line gene expression, ChIP-seq, and normal and
cancer tissue gene expression from the Genotype-Tissue Expression (GTEx), and the TCGA project, we have
identified LIPI as a highly specific tumor antigen and a potential oncogene that relies on the transcriptional activity
of EWS-FLI1 in Ewing sarcoma. LIPI (Lipase member I (EC:3.1.1.-) is an evolutionarily conserved protein
predicted to poses a transmembrane domain and extracellular lipid hydrolase domain. The biological function of
LIPI is not known but the enzymatic activity of LIPI is expected to produce lysophosphatidic acid (LPA) that
potently affects several biological functions including proliferation, cell survival, and metastasis of tumor cells.
We hypothesize that the LIPI is a unique biomarker and an oncogene that is expressed exclusively in Ewing
sarcoma and is a potential target for cell based therapy. To our knowledge, this proposal represents the first
study evaluating the role of LIPI in cellular physiology and in particular Ewing sarcoma progression and
metastasis. The two specific aims of the projects are:
Specific Aim 1: To elucidate the regulation and role of cell surface LIPI in Ewing sarcoma
Specific Aim 2: To investigate the role of LIPI in Ewing sarcoma growth/metastasis.
Following the successful completion of the proposed aims in this application, we will have evaluated the potential
of LIPI as a Ewing sarcoma specific surface oncoprotein, and will have a long-term impact by establishing the
strong foundation for the development of LIPI-directed immunotherapeutics against Ewing sarcoma.

## Key facts

- **NIH application ID:** 10883632
- **Project number:** 5R21CA274009-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Irfan Ahmed Asangani
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $216,512
- **Award type:** 5
- **Project period:** 2023-07-06 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10883632

## Citation

> US National Institutes of Health, RePORTER application 10883632, Discovery and characterization of exceptionally specific surface oncoprotein LIPI in Ewing Sarcoma (5R21CA274009-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10883632. Licensed CC0.

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