# Developing CluMPS reporters to visualize aggregation dynamics of receptor tyrosine kinase fusions

> **NIH NIH R35** · UNIVERSITY OF PENNSYLVANIA · 2021 · $33,665

## Abstract

Summary/Abstract
Protein aggregation plays a large role in normal cell physiology, but aberrant aggregation also underlies
numerous disease pathologies. It is often challenging to study such pathological aggregation, however, because
of our inability to visualize protein aggregates in diseased cells. Standard methods for visualization in live cells
include either overexpression of a fluorescently tagged construct or direct tagging of the endogenous protein
with a fluorescent tag. Not only do these techniques have significant limitations techniques including
overexpression artefacts, weak signal, and laborious preparation, but pathological aggregates are often small
and thus difficult to visualize through conventional live-cell microscopy. We have recently developed proof-of-
principle of a new class or reporter to provide straightforward visualization of endogenous protein aggregates
and their dynamics. The goal of this supplement will be to apply this reporter strategy to visualize endogenous
pathological aggregates in diseased cells. Specifically, we will target a class of oncogenes called receptor
tyrosine kinase fusions, which form protein aggregates within cells. We will design and validate reporter variants
that optimally detect and visualize the target aggregates. We will then visualize cluster dynamics across
independent cancer cell lines driven by the same receptor fusion. Finally, we will determine the extent to which
our reporter can be applied to visualize aggregation dynamics of distinct receptor fusions, of which over 50 have
been identified. The described work will validate our new reporter strategy for observation of cellular disease and
will have important implications for therapeutic development, for example by allowing visualization of multiple
disease states and by establishing a new assay for fluorescence-based drug screens.

## Key facts

- **NIH application ID:** 10321062
- **Project number:** 3R35GM138211-01S1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Lukasz Bugaj
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $33,665
- **Award type:** 3
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10321062

## Citation

> US National Institutes of Health, RePORTER application 10321062, Developing CluMPS reporters to visualize aggregation dynamics of receptor tyrosine kinase fusions (3R35GM138211-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10321062. Licensed CC0.

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