# Lipid regulation of cellular signaling and protein-protein interactions

> **NIH NIH R35** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $609,592

## Abstract

PROJECT SUMMARY/ABSTRACT
Lipid regulation of cellular signaling and protein-protein interactions
Eukaryotic cells can be regarded as a vast, extensively compartmentalized and hierarchic protein-
protein interaction (PPI) network. Characterizing PPI is therefore a crucial step in gaining an
understanding of how cells function. PPI has also emerged as an attractive target space for drug
development since PPI regulates numerous cellular processes, such as cell signaling. Despite the
wealth of PPI data, however, the mechanisms by which complex cellular PPIs are coordinated and
regulated with high spatiotemporal specificity are still poorly understood. This makes it difficult to
understand the mechanisms of cell regulation on a systems level and also hampers development of
specific drugs targeting PPI. Many PPI networks and protein complexes are formed on or near the cell
membranes, the plasma membrane in particular. However, direct involvement of membrane lipids in
coordination and modulation of PPI has not been explored. We have recently made breakthroughs in
this line of research and revolutionized the PPI research by establishing that lipids directly and
specifically regulate cellular PPI. This important new discovery as well as our innovative in situ
quantitative lipid imaging technology give us a unique and unparalleled opportunity to systematically
investigate how various lipids modulate PPI. We will study the mechanisms by which various lipids,
including cholesterol and phosphoinositides, regulate a wide variety of cellular processes by
spatiotemporally coordinating and modulating PPI through their specific interaction with protein
interaction domains, including PDZ and SH2 domains. We will also develop new small molecule
modulators of lipid-dependent PPI as drug candidates for various human diseases, including cancer.
Given the general and fundamental importance of PPI, our pioneering, innovative research should
have high potential impact on broad areas of biology and medicine.

## Key facts

- **NIH application ID:** 9898389
- **Project number:** 5R35GM122530-04
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** WONHWA CHO
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $609,592
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898389

## Citation

> US National Institutes of Health, RePORTER application 9898389, Lipid regulation of cellular signaling and protein-protein interactions (5R35GM122530-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9898389. Licensed CC0.

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