# Nuclear and chromatin aberrations during non-apoptotic cell death in C. elegans and mammals

> **NIH NIH K99** · ROCKEFELLER UNIVERSITY · 2024 · $124,999

## Abstract

Project Summary/ Abstract
The long-term goal of the proposed research is to uncover molecular mechanisms driving non-
apoptotic cell death in vertebrate development and disease, specifically the role of nuclear and
chromatin organization in this process. Programed cell death functions to sculpt organs, remodel tissues,
regulate cell number, and remove defective cells. While apoptosis is the most studied type of cell death, it
does not account for all cellular destruction during development. Studies in C. elegans have uncovered a
novel developmental cell death program, referred to as linker cell-type death (LCD), which is morphologically
and molecularly distinct from apoptosis. Cell death with LCD features is commonly observed during vertebrate
development and in neurodegenerative polyglutamine diseases, aggressive cancers, aging, progeria and
laminopathies. During my postdoctoral training, I uncovered striking nuclear and chromatin changes that
occur during LCD. This K99/R00 proposal seeks to identify the molecular regulatory processes
underlying these nuclear and chromatin changes during LCD in C. elegans, and to test the functional
conservation of LCD in a vertebrate context through the following specific aims: 1) Elucidate the role
of nuclear lamin and its regulation in the process of LCD (K99); 2) Establish a mouse model system to study
LCD in a developmental mammalian setting using degenerating Mullerian duct as a model (K99/R00); 3)
Identify molecular processes that govern chromatin dynamics during LCD in C. elegans and mammals (R00).
This proposal builds on my doctoral studies in mammalian epigenetics and chromatin, as well as postdoctoral
training investigating non-apoptotic cell death in C. elegans. During the mentored phase, I will gain essential
training in mouse organ culture and management, which will set me up to establish a robust and
innovative independent research program studying the contribution of chromatin and nucleus to the
non-apoptotic cell death in vertebrate and invertebrate systems, in addition to human disease. The
outstanding environment at the Rockefeller University, with mentorship from Dr. Shaham and my Advisory
Committee, will provide crucial expertise to facilitate my transition to independence. The studies proposed
here will lead to the development of new markers to distinguish among different types of cell death in
vertebrate development and disease, while uncovering the molecular underpinnings of LCD. Because LCD
is a prevalent type of cell demise, this proposal may not only shed light on basic aspects of development,
neurodegeneration, and cancer, but could also eventually uncover in-roads of clinical significance.

## Key facts

- **NIH application ID:** 10906950
- **Project number:** 5K99GM151467-02
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Olga Yarychkivska
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $124,999
- **Award type:** 5
- **Project period:** 2023-08-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906950

## Citation

> US National Institutes of Health, RePORTER application 10906950, Nuclear and chromatin aberrations during non-apoptotic cell death in C. elegans and mammals (5K99GM151467-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10906950. Licensed CC0.

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