# Characterizing an alternatively spliced NTRK2 isoform in development and cancer

> **NIH NIH K22** · SEATTLE CHILDREN'S HOSPITAL · 2022 · $187,056

## Abstract

Project Summary/Abstract
The link between developmental signaling and cancer initiation, maintenance and metastasis has long been
known for several members of the Wnt, Hedgehog, and Notch pathways. The possibility remains that a
developmentally-regulated splicing event may share similar features with these oncogenic pathways, driving
normal development in an anatomically appropriate, temporally restricted context, and causing cancer when
dysregulated. We have recently shown that a kinase-deficient NTRK2 neurotrophin receptor splice variant,
TrkB.T1, predominates in glioma and amplifies several oncogenic signaling pathways. Our preliminary data
suggest that TrkB.T1 is the predominate NTRK2 isoform expressed across multiple organs during embryonic
development, is highly expressed in various cancer types in humans, and when over-expressed in combination
with PTEN loss, causes a wide range of cancers in mice. The project proposed here seeks to characterize the
role TrkB.T1 in development and cancer using a novel antibody and a novel mouse model to show that specific
splice variants are oncogenic when overexpressed, postnatally, in the specific organs that expressed them
during development. By perturbing cell-specific TrkB.T1 splice variant expression in mice, embryonically, and
using single cell combinatorial indexing RNA-sequencing analysis to follow NTRK2 transcripts across embryonic
and postnatal development, I aim to (1) link developmental mechanisms and splicing choices to cancer, (2) link
a kinase deficient protein with increases in signaling, and (3) seek to discern whether trapping cells in a particular
developmental state can lead to cancer. By further characterizing the mechanism by which TrkB.T1 functions,
these projects have the potential to open new avenues for diagnostic and therapeutic targets for multiple cancer
types. The experiments proposed here build upon my previous work in neurodevelopment, neurotrophin biology,
and cancer and will help set the stage for my long-term career goals which center around employing a
developmentally guided approach to studying neurotrophic contributions to tumor biology and uncovering
developmental influences on oncogenesis.

## Key facts

- **NIH application ID:** 10490261
- **Project number:** 5K22CA258953-02
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Siobhan Pattwell
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $187,056
- **Award type:** 5
- **Project period:** 2021-09-24 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10490261

## Citation

> US National Institutes of Health, RePORTER application 10490261, Characterizing an alternatively spliced NTRK2 isoform in development and cancer (5K22CA258953-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10490261. Licensed CC0.

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