# Chemical Genetic Analysis of RAS Signaling

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2022 · $41,109

## Abstract

Abstract
The GTPase RAS functions as a molecular “on/off” switch, existing both in GDP-bound (inactive) and GTP-
bound forms (active). Despite functioning as a simple binary switch, RAS is capable of directing complex and
diverse cellular processes, including proliferation, migration, survival, and T-cell development. Recent work
suggests that the ability of RAS to play complex, often conflicting roles in diverse processes results from
differences in cellular context and and/or subcellular localization of its signaling. We have developed a novel
chemical genetic tool–called Chemically-Inducible Activator of RAS (CIAR)–to study the dynamics of the
signaling networks that are mediated by RAS activity. CIAR allows rapid and dose-dependent activation of
RAS signaling with a cell permeable small molecule. With CIAR, we propose to use targeted, quantitative
phosphoproteomics and transcriptomics to study the fundamental dynamic behavior of RAS-driven signaling.
Subcellularly-localized versions of CIAR will be used to determine the effects of localized RAS activation on the
dynamics of RAS-mediated signaling. We will also delineate the interplay between WT RAS and oncogenic
RAS signaling and the contribution of WT RAS-mediated signaling to direct inhibitors of oncogenic RAS
mutants. Finally, we will develop and use a chemically-controlled toolset for the rapid activation of signaling
enzyme oligomers, which will be used to dissect the role that oligomerization state plays in RAS signaling
dynamics.

## Key facts

- **NIH application ID:** 10642578
- **Project number:** 3R01GM145011-01A1S1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Dustin J Maly
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $41,109
- **Award type:** 3
- **Project period:** 2022-04-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10642578

## Citation

> US National Institutes of Health, RePORTER application 10642578, Chemical Genetic Analysis of RAS Signaling (3R01GM145011-01A1S1). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10642578. Licensed CC0.

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