# Understanding proteome remodeling in aneuploidy

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $376,875

## Abstract

ABSTRACT
Unbalanced chromosome content, so-called aneuploidy, is a hallmark of many human genetic diseases and
cancers. Aneuploidy not only results in the altered expression of the genes encoded on the aneuploid
chromosome, but also affects gene expression genome-wide. For many aneuploidy related diseases, it is still
not clear which gene or gene sets are the key drivers of disease pathology. Research on molecular
consequences of aneuploidy could shed invaluable light on “genotype-phenotype” association, thus leading to
a better understanding of disease development mechanisms. Due to the known substantial post-transcriptional
processes in aneuploidy condition and the functional importance of proteins, proteomic measurement is
indispensable to identify genes that are dosage-imbalanced at the protein level. However, biological and
technical challenges such as the variability of the individual genome, the limited quantitative reproducibility and
accuracy of the measurement, and the lack of strategies for identifying indirect mechanisms have hindered
efficient proteomic scrutiny on aneuploidy. We hypothesize that the aneuploid cells would employ characteristic
proteostasis and cell signaling pathways to deal with the large-scale protein dosage imbalance, and that the
newly acquired or altered protein-protein interactions under aneuploidy stress play an important role in
regulating molecular network and cellular fitness. In this proposal, we will use isogenic cell models from human
and mouse aneuploidy cases. We will further develop and apply the techniques based on quantitative mass
spectrometry and new analytical strategies based on protein- context profiling to discover the direct and
indirect proteomic effects in the aneuploidy models. Results from this proposal are extremely important. First,
the proteomic- centric, multilayered dataset will describe how protein homeostasis is maintained when several
hundreds of genes that are gained or lost, decipher commonly activated signaling processes across
aneuploidy models, and provide opportunities to predict the cellular impact of specific gene copy number
alteration (CNA). Second, the protein-context profiling technique will be an invaluable tool for identifying de
novo protein functions and associations in aneuploidy and other disease conditions. Third, those significant
proteins escaping the homeostasis control or tightly interacting to signaling hubs will provide a list of important
protein targets for further functional studies in aneuploidy cases, such as lung squamous cell carcinomas and
trisomy disorders that are relevant to the studied cell models.

## Key facts

- **NIH application ID:** 10836483
- **Project number:** 5R01GM137031-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Yansheng Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $376,875
- **Award type:** 5
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10836483

## Citation

> US National Institutes of Health, RePORTER application 10836483, Understanding proteome remodeling in aneuploidy (5R01GM137031-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10836483. Licensed CC0.

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