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Epigenetic regulation of lineage specification in colon epithelial cells

Award Number: F32DK135241
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 03/01/2023
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Epigenetic regulation of lineage specification in colon epithelial cells - PROJECT SUMMARY The colon is a responsive tissue, and the epithelium replaces itself every 3-4 days. The colon has dedicated stem cells that divide for self-renewal and differentiation into specialized cell types. Differentiated colon cells perform distinct functions including water absorption and mucus secretion. In many tissues, differentiation is driven by epigenetic mechanisms including histone modifications. Methylation of histone H3 at lysine 36 (H3K36) is associated with gene bodies at sites of transcriptional activity. H3K36 methylation contributes to differentiation and stem cell maintenance in rapidly renewing tissues including blood and testes. Based on preliminary data, I hypothesize that H3K36 methylation governs cell fate decisions and reinforces cell identity in colon epithelial cells, specifically colonocyte and goblet cell lineages. To address this hypothesis, I will pursue two specific aims. First, I plan to characterize the H3K36 methylation signature in colon epithelial cells. Second, I will determine the functional role of H3K36 methylation in colon cell identity. Although, establishing a direct connection between specific histone modifications and cellular processes is challenging due to redundancies in the system, I can overcome this obstacle by taking advantage of a lysine (K)-to-methionine (M) mutation first discovered in cancer patients to precisely suppress H3K36 methylation. I will combine multiple cutting-edge tools to specifically trace and manipulate H3K36 methylation in mice and organoid model systems to advance the understanding of chromatin and lineage specification in the colon. I will also utilize novel sorting protocols to purify distinct colon cell populations for comparative epigenetic and transcriptional analysis. Collectively, this work is significant because it will establish the role of H3K36 methylation in controlling cell-type specific gene expression and lineage decisions in the colon. Revealing the role histone modifications play in colon homeostasis is the first step to understanding how these regulatory mechanisms break down in diseases such as colitis/cancer and could impact human health.


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 = $80,224 )
2025	2025	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	1/8/2025	NON-COMPETING CONTINUATION	$78,892
2025	2025	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	6/10/2025	NON-COMPETING CONTINUATION	$1,332
														Subtotal = $80,224

Issue Date FY: 2024 ( Subtotal = $76,756 )
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	1/25/2024	NON-COMPETING CONTINUATION	$71,792
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	4/29/2024	NON-COMPETING CONTINUATION	$4,964
														Subtotal = $76,756

Issue Date FY: 2023 ( Subtotal = $69,500 )
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	2/22/2023	NEW	$0
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	1	2/22/2023	NEW	$0
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	2/22/2023	NEW	$69,500
														Subtotal = $69,500

Grand Total All Awards = $226,480

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Epigenetic regulation of lineage specification in colon epithelial cells

Award Number: F32DK135241

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 03/01/2023

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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