# Project 2: Regulation of Pre-mRNA Splicing in Tumorigenesis

> **NIH NIH P01** · COLD SPRING HARBOR LABORATORY · 2020 · $663,644

## Abstract

PROJECT SUMMARY - PROJECT 2
The central goal of Project 2 is to understand the various roles of alternative splicing in cancer, and to exploit
cancer-specific features of this process to develop targeted-therapeutic approaches. Cancer cells display
extensive qualitative and quantitative dysregulation of splicing, and a subset of the numerous isoforms that are
inappropriately expressed contribute to tumorigenesis or altered cell metabolism. The mechanisms and
pathways through which the splicing-factor oncoproteins SRSF2 and SRSF1 transform cells will continue to be
investigated. Cell-culture models, as well as orthotopic and genetic mouse models will be used to study
tumorigenesis promoted by these splicing factors upon mutation or overexpression in different cancer contexts,
with an emphasis on recurrent mutations in myeloid dysplasias. High-throughput RNA-sequencing and
computational analysis will be employed to identify and compare the splicing targets of these SR proteins in
different cancer contexts, and selected targets will be characterized and manipulated to evaluate their
contributions to tumorigenesis and potential as therapeutic targets or biomarkers. One key event, alternative
splicing of pyruvate kinase pre-mRNA, which controls the distinctive glycolytic metabolism of cancer cells, will
be thoroughly investigated as a potential therapeutic target, by specifically manipulating this process in vivo,
using antisense technology and mouse models of glioma and hepatocellular carcinoma.

## Key facts

- **NIH application ID:** 9851820
- **Project number:** 5P01CA013106-48
- **Recipient organization:** COLD SPRING HARBOR LABORATORY
- **Principal Investigator:** Adrian R Krainer
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $663,644
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851820

## Citation

> US National Institutes of Health, RePORTER application 9851820, Project 2: Regulation of Pre-mRNA Splicing in Tumorigenesis (5P01CA013106-48). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9851820. Licensed CC0.

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