# RNA-Binding Proteins as Molecular Integrators that Control the Response of HGSOC to Ant-Cancer Therapies

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $536,497

## Abstract

Project Summary
 Ovarian carcinoma is the fifth deadliest cancer among women in the United States. In spite of advances
in surgical resection and platinum-taxane combination therapy over the past several decades, cure rates
remain relatively low (~30%) and a majority of women diagnosed with advanced ovarian cancer will die with
drug-resistant disease within 5 years. The long-term goal of this project, “RNA-Binding Proteins as Molecular
Integrators that Control the Response of HGSOC to Anti-Cancer Therapies”, is to identify specific RNA-binding
proteins that, together with their upstream protein kinase regulators, control the resistance and sensitivity of
high-grade serous ovarian cancers to these clinically used first line anti-cancer therapies. The project involves:
(1) a detailed computational analysis that queries pre-existing publically available RNA expression data using
RNA-BP recognition motifs to identify specific RNA binding proteins whose mRNA targets are up- or down-
regulated in ovarian cancer patients with chemo-sensitive versus chemo-resistant tumors; and (2) an
independent CRISPR-interference and CRISPR-activation genome-wide screen for RNA-BPs whose
manipulation alters the resistance and sensitivity of ovarian cancer cells to platinum and taxane agents in vitro,
and in vivo using cell line xenografts and human PDX ovarian cancer mouse models. The RNA-BPs identify
by these two complimentary approaches, together with a collection of RNA-BPs that we have already identified
in previous experiments and preliminary data, are then directly validated for their effects on drug resistance in
these model systems, and the identity of their bound RNAs and their effects on gene expression determined
using CLIP technologies and RNA-Seq. In selected cases the importance of specific phosphorylation sites on
RNA-BP function is examined to further elucidate the molecular basis for anti-cancer drug resistance through
pathway-specific regulation of RNA-BP action. The project builds on a broad foundation of expertise and
related work from all of the co-Investigators laboratories. Expected outcomes from the studies include the
identification of specific RNA-BPs and upstream regulatory kinase pathways whose targeting can prevent or
reverse the resistance of ovarian cancers to current clinically used front-lime therapeutics; the elucidation of
new molecular circuits that control gene expression in cancers after chemotherapy treatment; and the creation
of a suite of web-based tools available to the entire scientific community that can be used to query any set of
differentially expressed genes for RNA-BP-based regulation, particularly in a form that is optimized for analysis
of new and existing cancer patient RNA expression datasets.

## Key facts

- **NIH application ID:** 10054974
- **Project number:** 5R01CA226898-03
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** CHRISTOPHER B BURGE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $536,497
- **Award type:** 5
- **Project period:** 2018-12-07 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10054974

## Citation

> US National Institutes of Health, RePORTER application 10054974, RNA-Binding Proteins as Molecular Integrators that Control the Response of HGSOC to Ant-Cancer Therapies (5R01CA226898-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10054974. Licensed CC0.

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