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Mechanisms that underlie the life/death decisions in a cell that activated apoptotic caspases

Award Number: F31GM149184
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/01/2023
PERIOD OF PERFORMANCE END DATE: 08/18/2024

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Mechanisms that underlie the life/death decisions in a cell that activated apoptotic caspases - Mechanisms that underlie the life/death decisions in a cell that activated apoptotic caspases More than half of cancer patients undergo ionizing radiation (IR) treatment. IR-therapy success relies on causing enough DNA damage in cells to force them to complete the process of programmed-cell death, known as apoptosis. Unfortunately, some cells can survive exposure to radiation and regenerate tumors, leading to treatment failure (radioresistance). Since radiotherapy is one of the three most common treatments used against cancer, understanding how cells survive after exposure to radiation is crucial for radiotherapy optimization. When a cell gets damaged by IR, a death signal is triggered in the cell leading to the activation of apoptotic caspases. Apoptotic caspases were once thought to be hallmarks of apoptosis. However, it is now known that some cells may activate apoptotic caspases but do not die after exposure to radiation. How cells survive after activating apoptotic caspases remains an active area of research. Thus, the goal of this proposal is to elucidate how cells survive caspase activity after radiation exposure. I use Drosophila melanogaster, commonly known as fruit fly, to study how cells survive caspase activity. Cell death, including caspases, and regeneration in Drosophila share genetic and molecular features with vertebrates, thus, what we learn from this model organism will likely be translatable to humans. In Aim 1, I will determine the mechanisms/genes that underlie the life/death decisions in a cell that activated apoptotic caspases. Specifically, I will identify the signaling pathways that are involved in the regulation of cells that experience apoptotic caspase activity but do not die. I have decided to target different signaling pathways that are known to be critical for cell survival in flies and humans, such as Wnt (wingless in flies) and Notch signaling pathways. I anticipate this work will reveal the genes that contribute to life/death decision of the cell, which will provide a foundation for understanding how cancer cells survive after exposure to IR. In Aim 2, I will investigate the consequences of having cells that survive caspase activity but do not die. I am interested in understanding how stable the DNA of these cells is after surviving exposure to IR and the role of caspases in DNA repair. These studies will bring new insights to new/novel non-lethal roles of apoptotic caspases that could be exploited to improve radiotherapy. Collectively, this work will provide a comprehensive understanding of the role of caspases in aiding cells survive after exposure to radiation and it also will identify mechanisms that may be modulated to improve treatment outcome in human cancers.


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: 2025 ( Subtotal = -$15,756 )
2025	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Biomedical Research and Research Training	000	2	11/1/2024	NON-COMPETING CONTINUATION	-$10,348
2025	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80303	BOULDER	USA	Biomedical Research and Research Training	001	2	6/25/2025	NON-COMPETING CONTINUATION	-$5,408
														Subtotal = -$15,756

Issue Date FY: 2024 ( Subtotal = $41,925 )
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Biomedical Research and Research Training	001	2	6/11/2024	NON-COMPETING CONTINUATION	$1,280
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Biomedical Research and Research Training	000	2	12/20/2023	NON-COMPETING CONTINUATION	$40,645
														Subtotal = $41,925

Issue Date FY: 2023 ( Subtotal = $40,384 )
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Biomedical Research and Research Training	000	1	1/1/2023	NEW	$39,442
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Biomedical Research and Research Training	003	1	3/1/2023	NEW	$942
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Biomedical Research and Research Training	001	1	1/1/2023	NEW	$0
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Biomedical Research and Research Training	002	1	1/25/2023	NEW	$0
														Subtotal = $40,384

Grand Total All Awards = $66,553

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Mechanisms that underlie the life/death decisions in a cell that activated apoptotic caspases

Award Number: F31GM149184

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/01/2023

PERIOD OF PERFORMANCE END DATE: 08/18/2024

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