Tuesday, July 1, 2025 7/1/2025

Cell cycle control of cell polarity and fate in epidermal morphogenesis

Award Number: R01AR068320
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/16/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Cell cycle control of cell polarity and fate in epidermal morphogenesis - Loss of cell polarity and invasive behavior are hallmarks of cancer, but how cell polarity is preserved during tissue growth and turnover is poorly understood. Polarity refers to the asymmetric partitioning of membrane components and subcellular structures, is oriented along both apicobasal and planar axes, and is essential for the proper assembly and function of epithelial tissues. The preservation of cell polarity is of crucial importance in tumor suppression and therefore, special mechanisms must exist to preserve polarity when cells divide. We have shown that to preserve tissue architecture, epithelial polarity is dynamically remodeled when cells divide. Asymmetrically localized polarity proteins are temporarily removed from the cell surface via bulk endocytosis into the cytoplasm. After division, they are recycled to the surface where polarity is restored. This mechanism is controlled directly by mitotic kinases, the same machinery that controls cell cycle progression and is deregulated in cancer. Thus, cell division and planar cell polarity are controlled by the same regulatory machinery, and may explain why, in cancer, hyperproliferation and cellular disorder are so closely intertwined. In this proposal we build and expand on this foundational work to investigate how cell polarity is restored after mitosis and how cell division facilitates the establishment of robust and aligned tissue polarity. We will capitalize on our recent technical advancements in live and super-resolution imaging of the skin to 1) decipher the transport mechanisms that restore polarity following mitosis and how mitotic repolarization establishes tissue-scale polarity; 2) define the spatial cues that direct mitotic repolarization; and 3) determine how neighboring cells coordinate mitotic removal of intercellular junctions via transendocytosis. Successful completion of ours aims will uncover the mechanisms by which a highly proliferative epithelium preserves tissue integrity.


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 = $408,521 )
2025	2025	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	8	1/23/2025	NON-COMPETING CONTINUATION	$408,521
														Subtotal = $408,521

Issue Date FY: 2024 ( Subtotal = $438,058 )
2024	2024	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	7	6/4/2024	NON-COMPETING CONTINUATION	$31,613
2024	2024	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	7	1/10/2024	NON-COMPETING CONTINUATION	$406,445
														Subtotal = $438,058

Issue Date FY: 2023 ( Subtotal = $574,998 )
2023	2023	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	2/15/2023	COMPETING CONTINUATION	$574,998
														Subtotal = $574,998

Issue Date FY: 2022 ( Subtotal = -$101,957 )
2022	2020	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	9/8/2022	NON-COMPETING CONTINUATION	-$101,957
														Subtotal = -$101,957

Issue Date FY: 2020 ( Subtotal = $346,743 )
2020	2020	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	4/30/2020	NON-COMPETING CONTINUATION	$423,647
2020	2020	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	5	5/26/2020	NON-COMPETING CONTINUATION	-$76,904
														Subtotal = $346,743

Issue Date FY: 2019 ( Subtotal = $423,647 )
2019	2019	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	4/29/2019	NON-COMPETING CONTINUATION	$423,647
														Subtotal = $423,647

Issue Date FY: 2018 ( Subtotal = $461,297 )
2018	2018	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	11/1/2017	SUPPLEMENT FOR EXPANSION	$37,650
2018	2018	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	5/25/2018	NON-COMPETING CONTINUATION	$423,647
														Subtotal = $461,297

Issue Date FY: 2017 ( Subtotal = $346,743 )
2017	2017	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	6/14/2017	NON-COMPETING CONTINUATION	$34,675
2017	2017	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	5/5/2017	NON-COMPETING CONTINUATION	$312,068
														Subtotal = $346,743

Issue Date FY: 2016 ( Subtotal = $346,743 )
2016	2016	PRINCETON UNIVERSITY	POST OFFICE BOX 5292	PRINCETON	NJ	08544	MERCER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	5/5/2016	NEW	$346,743
														Subtotal = $346,743

Grand Total All Awards = $3,244,793

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Cell cycle control of cell polarity and fate in epidermal morphogenesis

Award Number: R01AR068320

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/16/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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