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

Award Number: K99GM151467
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/15/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2024	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	000	2	3/13/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $124,999 )
2024	2024	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	000	2	7/31/2024	NON-COMPETING CONTINUATION	$124,999
2024	2023	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	001	1	8/1/2024	NEW	$0
														Subtotal = $124,999

Issue Date FY: 2023 ( Subtotal = $124,999 )
2023	2023	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Biomedical Research and Research Training	000	1	8/14/2023	NEW	$124,999
														Subtotal = $124,999

Grand Total All Awards = $249,998

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

Award Number: K99GM151467

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/15/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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