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Metabolic and epigenetic drivers of stem cells in obesity and cancer

Award Number: K22CA241083
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/16/2020
PERIOD OF PERFORMANCE END DATE: 07/31/2023

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Metabolic and epigenetic drivers of stem cells in obesity and cancer - Project Abstract Title: Metabolic and epigenetic drivers of stem cells in obesity and cancer PI: Miyeko Mana Our understanding of the relationship between diet, stem cells, and cancer is central to the prevention and treatment of this disease. With rising levels of obesity and the associated risk of cancer there is greater need to understand mechanisms by which diet influences tissue-specific stem cells that lead to oncogenic transformation. We have shown that a pro-obesity high-fat diet (HFD) increases stem cell number and niche independent growth in the mammalian intestine. We demonstrated that a HFD promotes stem cell self-renewal and tumorigenesis through the activation of a robust peroxisome proliferator-activated receptor delta (PPAR-δ) signature. Importantly, we showed these properties were bestowed upon the progenitor population thereby expanding the pool of cells capable of malignant growth. Our preliminary results indicate that multiple members of the PPAR family are required to establish the HFD phenotype in intestinal stem cells, and that PPAR redundancy signals the importance of downstream effectors. The biochemical and molecular underpinnings of the HFD will emerge through identification of the mechanistic steps that alter basic metabolism and epigenetic maintenance of the HFD transcriptional state. Our overall hypothesis is that a HFD markedly influences the metabolism and the stability of a PPAR transcriptional program that impact intestinal stem cells, tumor initiation and progression. We will test the premise that (Aim1) a HFD or agonist-activated PPAR establishes a state of dependency on the metabolic fatty acid oxidation program, and (Aim2) a HFD induces a stable transcriptional state by perturbing the chromatin landscape through chronic PPAR activity.


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: 2024 ( Subtotal = $0 )
2024	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Cancer Research Manpower	000	3	2/28/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $177,120 )
2022	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Cancer Research Manpower	000	3	7/7/2022	NON-COMPETING CONTINUATION	$177,120
														Subtotal = $177,120

Issue Date FY: 2021 ( Subtotal = $177,134 )
2021	2021	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Cancer Research Manpower	000	2	7/26/2021	NON-COMPETING CONTINUATION	$177,134
														Subtotal = $177,134

Issue Date FY: 2020 ( Subtotal = $177,149 )
2020	2020	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Cancer Research Manpower	000	1	7/15/2020	NEW	$177,149
														Subtotal = $177,149

Grand Total All Awards = $531,403

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Metabolic and epigenetic drivers of stem cells in obesity and cancer

Award Number: K22CA241083

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/16/2020

PERIOD OF PERFORMANCE END DATE: 07/31/2023

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