# Chromosomal Instability and 17p Loss Sensitize Cancer Cells to NDE1 Depletion

> **NIH NIH F31** · DUKE UNIVERSITY · 2024 · $48,290

## Abstract

PROJECT SUMMARY
Chromosomal Instability (CIN) and loss of the short arm of chromosome 17 (17p) are interrelated and relatively
common characteristics of many advanced, metastatic cancers. Though these genetic alterations are likely to
contribute to synthetic lethalities, the genetic dependencies resulting from CIN and 17p loss have not been
extensively identified or explored. A whole-genome CRISPR/Cas9 screen performed in our lab comparing
primary and metastatic-derivative cell lines revealed that metastatic tumors, which possess higher rates of
chromosomal instability, are more sensitive to inhibition of mitotic regulators associated with chromosome
segregation. Knockout of one such regulator, NDE1, selectively inhibited the growth of metastatic, CIN-high
cell lines in vitro, and in vivo. Interestingly, dependence on NDE1 is highly correlated with loss of 17p across
cell lines in the DepMap database, indicating that both CIN and 17p loss may contribute to NDE1 sensitivity.
We hypothesize that inhibiting NDE1 may be an effective way to target cancers harboring 17p loss and
increased CIN through a unique, dual action mechanism involving the buildup of errors in faithful chromosome
segregation, and synthetic lethality with an NDE1 paralog and binding partner, both of which are located on
17p. To test this central hypothesis, I propose defining the relationship between NDE1 dependence, 17p loss,
and chromosomal instability, characterizing the role of NDE1 in proper chromosome segregation, and
assessing the therapeutic potential of targeting NDE1 in the context of CIN and 17p loss.

## Key facts

- **NIH application ID:** 10820671
- **Project number:** 1F31CA287604-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Caroline Marie Teddy
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,290
- **Award type:** 1
- **Project period:** 2024-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10820671

## Citation

> US National Institutes of Health, RePORTER application 10820671, Chromosomal Instability and 17p Loss Sensitize Cancer Cells to NDE1 Depletion (1F31CA287604-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10820671. Licensed CC0.

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