# Lipid regulation of cellular signaling and protein-protein interactions

> **NIH NIH R35** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2024 · $245,385

## Abstract

WONHWA CHO, PH.D.
PROJECT SUMMARY/ABSTRACT
Lipid regulation of cellular signaling and protein-protein interactions
Cellular proteins accomplish their functions through interactions with other proteins, forming complex
protein-protein interaction networks. Cellular protein-protein interaction typically involves small
modular protein interaction domains, such as Src-homology 2 and PSD95, Dlg1, ZO-1 domains.
Physiological significance of protein interaction domain-mediated protein-protein interaction networks
has been well supported by a large number of protein interaction domains encoded by human
genome and many human diseases, including cancer, caused by dysfunctional protein interaction
domain-mediated cellular processes. Interestingly, most protein interaction domains have moderate
binding affinity and a significant degree of promiscuity. This may be necessary for reversibility and
redundancy of cell signaling pathways but raises a fundamental question as to how high-fidelity
cellular function and regulation can be achieved through the protein interaction domain-mediated
protein-protein interaction. We have recently shown that membrane lipids, including cholesterol and
phosphoinositides, coordinate and regulate protein-protein interaction by directly and specifically
interacting with protein interaction domains. This important new discovery and our innovative in situ
quantitative lipid imaging technology provide us with a unique and unparalleled opportunity to
elucidate the mechanisms by which lipids orchestrate spatiotemporal specificity of protein-protein
interaction and cell signaling and develop new strategies to modulate these processes. Given the
importance of protein interaction domain-mediated protein-protein interaction and cell signaling in
health and disease, our proposed research should have a major impact on broad areas of biology and
medicine and lay the foundation for a pioneering and innovative drug discovery strategy for human
diseases, most notably cancer.

## Key facts

- **NIH application ID:** 11037033
- **Project number:** 3R35GM122530-07S1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** WONHWA CHO
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $245,385
- **Award type:** 3
- **Project period:** 2017-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11037033

## Citation

> US National Institutes of Health, RePORTER application 11037033, Lipid regulation of cellular signaling and protein-protein interactions (3R35GM122530-07S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11037033. Licensed CC0.

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