# Towards a comprehensive roadmap of cellular signaling.

> **NIH NIH R35** · UNIVERSITY OF WASHINGTON · 2020 · $381,503

## Abstract

ABSTRACT
Cells continuously sense, integrate, and process environmental parameters to inform physiological outcomes,
(e.g. how to utilize glucose or whether to enter mitosis). Protein phosphorylation is the most extensively
studied mechanism by which cells rapidly sense signals and execute decisions. Summarizing these events with
simple models has proved a valuable way for investigators to conceptualize signaling pathways and formulate
new hypotheses. However, without discovery experiments it is difficult to ascertain comprehensive models.
Models missing key components lead to misdirected hypotheses, and thus present a major barrier to
understanding cellular decisions. More than one hundred thousand mammalian phosphorylation sites have
been described to date, but systematic quantitative data on their regulation by relevant signaling pathways
within individual cell-types remains scarce. This type of data is necessary to build predictive models and to
understand what goes wrong in complex scenarios like insulin resistance or cancer.
In the short term we will develop and use mass spectrometry-based phosphoproteomics to systematically
interrogate the signaling network and reveal the design principles of signal integration. This knowledge will be
crucial to understanding why different cell types respond differently to the same stimuli to accomplish different
functions. We will also focus on providing a functional context to novel phosphorylation sites we discovered on
ubiquitin, and that connect phosphorylation-driven signaling to signaling mediated by ubiquitin.
In the long term, we shall be able to predict cellular behavior from measuring a relevant set of phosphorylation
events. For example we will be able to predict how cancer cells respond to a particular drug. Furthermore, we
will have detailed knowledge of the signaling nodes that are suitable for intervention in disease conditions,
reverting the malignant phenotype without inferring with other cellular functions. Finally, we will be able to
program cellular phenotypes, for example increasing the production of a particular metabolite, or modulating
migratory ability.

## Key facts

- **NIH application ID:** 9982383
- **Project number:** 5R35GM119536-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Judit Villen
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,503
- **Award type:** 5
- **Project period:** 2016-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982383

## Citation

> US National Institutes of Health, RePORTER application 9982383, Towards a comprehensive roadmap of cellular signaling. (5R35GM119536-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9982383. Licensed CC0.

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