# Mechanisms regulating nuclear envelope structure and stability

> **NIH NIH R35** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2021 · $272,348

## Abstract

PROJECT SUMMARY
The nuclear envelope (NE) has long been thought to function as a static barrier during interphase that
regulates interactions between cytosolic proteins and the chromatin. However, recent work challenges this
assumption. NE rupture, which results in the transient or permanent loss of nucleus compartmentalization, has
been observed in dividing and migrating cells and occurs with increased frequency in cells from laminopathy
and cancer patients. Current research has demonstrated that NE rupture can have significant consequences
for gene expression, chromatin structure, aneuploidy, and genome stability. However, we have almost no
information about the mechanisms driving NE rupture and repair and, thus, we have been unable to rigorously
define the cellular consequences. This is due, in part, to our limited understanding of the structure of the NE,
particularly lamin network organization, and how structural changes are regulated. The goals of our current
research program are 1) to identify the mechanisms of NE rupture and repair, and 2) to develop new tools to
analyze NE structure. We plan to achieve these goals by performing a genome-wide RNAi screen in cancer
cells to identify regulators of NE stability, and designing new image analysis programs and live-cell imaging
reporters to study the 3D dynamics and physical properties of the NE. We are at the beginning of defining
the NE as a dynamic structure. Thus, the long-term goals of this research program are to identify the
fundamental principles regulating NE dynamics and determine the molecular mechanisms by which defects in
NE stability impact disease. Identifying the proteins and pathways that regulate NE rupture and repair will
redefine our understanding of NE structure and have broad impacts on associated fields, including
chromosome organization and chromatin structure, transcription regulation, cellular responses to mechanical
force, and DNA replication and repair, and on larger questions about cell differentiation, tissue development,
aging, and cancer initiation and progression.

## Key facts

- **NIH application ID:** 10226315
- **Project number:** 5R35GM124766-05
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Emily M Hatch
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $272,348
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10226315

## Citation

> US National Institutes of Health, RePORTER application 10226315, Mechanisms regulating nuclear envelope structure and stability (5R35GM124766-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10226315. Licensed CC0.

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