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Cell adhesion and tissue dynamics in the skin

Award Number: R37AR027883
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: 12/01/1980
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Cell adhesion and tissue dynamics in the skin - Project Summary Our global objective is to develop a molecular understanding of how during development a population of stem cells (SCs) are set aside to produce, maintain and regenerate our tissues. As our longstanding AR27883 research on skin has shown, our basic science approach has led to advances in regenerative medicine and our understanding of human syndromes. Our skin epidermis is our body's barrier to the outside world: it must keep harmful microbes out and retain essential body fluids. Our current research centers on how emerging tissue SCs sense and interact with their surroundings (cells, signals and mechanical forces) not only to achieve a balance of proliferation and differentiation, but also to eliminate underperforming tissue cells as they arise. Understanding how healthy epidermal SCs arise and how they perform their duties is prerequisite to unraveling how cellular organization goes awry in inflammatory disorders and cancers of the skin. During skin development, stratified epidermis (and its hair follicle appendages) forms from a single layer of unspecified progenitors. As morphogenesis proceeds, resident epidermal SCs are set aside so that in adult skin, these self-renewing progenitors maintain and repair the skin's barrier. To what extent do self and non-self epidermal SC neighbors, and the mechanical forces they generate, participate in regulating SC behavior during normal homeostasis? What is the molecular nature of this communication circuitry that balances epidermal growth and differentiation? In the next 5 years, we'll: (1). Spatially map the temporal dynamics of cells and their transcriptomes as embryonic skin progenitors interact with newly emerging self and/or non-self neighbors, which together shape the niches that allow progenitors to behave as mature SCs with defined tasks. (2). Identify key signaling inputs that orchestrate the continual flux of epidermal progenitors and differentiating progeny that maintains and rejuvenates the body's barrier. (3). Elucidate how epidermis eliminates poorly performing cells for the sake of tissue fitness. (4). Elucidate how key signaling pathways and transcriptional events drive different regional mechanical forces during skin development and contribute to distinct morphologies and tissue functions. We'll apply the knowledge gained to determine how deviations in stem cell crosstalk with neighbors (`niche') lead to disease. To meet our aims, we and our collaborators developed unprecedented tools to a) spatiotemporally landscape gene expression across the skin, b) interrogate how mechanical forces impact tissue biology and c) track and characterize SCs as they sense and eliminate aberrant neighbors to preserve tissue fitness. While promising for regenerative medicine, adult tissue stem cells are long-lived and can also accumulate mutations that compromise tissue fitness and enhance cancer susceptibility. By unraveling how healthy SCs eliminate aberrantly performing cells, and yet over time, allow phenotypically silent oncogenic clonal diversity to accumulate, we aim to advance therapeutics to halt cancers before they appear. Our work on how mechanical forces impact SC behavior will be equally key in understanding how aggressive cancers arise.


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 = $707,095 )
2026	2026	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	48	7/21/2026	NON-COMPETING CONTINUATION	$707,095
														Subtotal = $707,095

Issue Date FY: 2025 ( Subtotal = $669,880 )
2025	2025	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	47	8/20/2025	NON-COMPETING CONTINUATION	$669,880
														Subtotal = $669,880

Issue Date FY: 2024 ( Subtotal = $721,980 )
2024	2024	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	46	9/5/2024	NON-COMPETING CONTINUATION	$721,980
2024	2023	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	45	4/8/2024	COMPETING CONTINUATION	$0
														Subtotal = $721,980

Issue Date FY: 2023 ( Subtotal = $744,310 )
2023	2023	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	45	6/21/2023	COMPETING CONTINUATION	$744,310
														Subtotal = $744,310

Issue Date FY: 2019 ( Subtotal = -$198,766 )
2019	2018	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	39	12/31/2018	NON-COMPETING CONTINUATION	-$198,766
														Subtotal = -$198,766

Issue Date FY: 2018 ( Subtotal = $785,316 )
2018	2018	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	39	5/3/2018	NON-COMPETING CONTINUATION	$78,533
2018	2018	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	39	8/6/2018	NON-COMPETING CONTINUATION	$0
2018	2018	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	39	11/22/2017	NON-COMPETING CONTINUATION	$706,783
														Subtotal = $785,316

Issue Date FY: 2017 ( Subtotal = $785,316 )
2017	2017	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	38	6/14/2017	NON-COMPETING CONTINUATION	$78,533
2017	2017	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	38	11/16/2016	NON-COMPETING CONTINUATION	$706,783
														Subtotal = $785,316

Issue Date FY: 2016 ( Subtotal = $785,316 )
2016	2016	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	37	1/21/2016	NON-COMPETING CONTINUATION	$78,533
2016	2016	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	37	11/10/2015	NON-COMPETING CONTINUATION	$706,783
														Subtotal = $785,316

Issue Date FY: 2015 ( Subtotal = $785,316 )
2015	2015	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	36	12/19/2014	NON-COMPETING CONTINUATION	$78,533
2015	2015	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	36	11/19/2014	NON-COMPETING CONTINUATION	$706,783
														Subtotal = $785,316

Issue Date FY: 2014 ( Subtotal = $785,316 )
2014	2014	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	35	3/31/2014	EXTENSION WITH OR WITHOUT FUNDS	$127,664
2014	2014	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	35	1/27/2014	EXTENSION WITH OR WITHOUT FUNDS	$657,652
														Subtotal = $785,316

Issue Date FY: 2013 ( Subtotal = $730,724 )
2013	2013	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	34	11/30/2012	NON-COMPETING CONTINUATION	$692,265
2013	2013	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	34	7/17/2013	NON-COMPETING CONTINUATION	$38,459
														Subtotal = $730,724

Issue Date FY: 2012 ( Subtotal = $769,183 )
2012	2012	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	33	2/3/2012	NON-COMPETING CONTINUATION	$63,074
2012	2012	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	33	11/17/2011	NON-COMPETING CONTINUATION	$706,109
														Subtotal = $769,183

Issue Date FY: 2011 ( Subtotal = $769,183 )
2011	2011	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	32	11/18/2010	NON-COMPETING CONTINUATION	$720,236
2011	2011	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	32	7/28/2011	NON-COMPETING CONTINUATION	$48,947
														Subtotal = $769,183

Issue Date FY: 2010 ( Subtotal = $776,955 )
2010	2010	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	31	1/14/2010	NON-COMPETING CONTINUATION	$70,633
2010	2010	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	31	12/4/2009	NON-COMPETING CONTINUATION	$706,322
														Subtotal = $776,955

Issue Date FY: 2009 ( Subtotal = $1,016,539 )
2009	2009	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Trans-NIH Recovery Act Research Support	001	30	9/18/2009	SUPPLEMENT FOR EXPANSION	$256,474
2009	2009	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	30	1/30/2009	COMPETING CONTINUATION	$760,065
														Subtotal = $1,016,539

Issue Date FY: 2003 ( Subtotal = $687,369 )
2003	2003	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	24		NON-COMPETING CONTINUATION	$687,369
														Subtotal = $687,369

Issue Date FY: 2002 ( Subtotal = $603,165 )
2002	2002	ROCKEFELLER UNIVERSITY	EAST 66TH STREET & YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	23	6/28/2002	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$462,405
2002	2002	UNIVERSITY OF CHICAGO	1225 EAST 60TH ST	CHICAGO	IL	60637	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	22	6/28/2002	NON-COMPETING CONTINUATION	$140,760
														Subtotal = $603,165

Issue Date FY: 2001 ( Subtotal = $550,295 )
2001	2001	UNIVERSITY OF CHICAGO	1225 EAST 60TH ST	CHICAGO	IL	60637	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	21	1/23/2001	NON-COMPETING CONTINUATION	$550,295
														Subtotal = $550,295

Issue Date FY: 2000 ( Subtotal = $535,281 ) (Continued on the next page)
Grand Total All Awards = $14,007,352

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Cell adhesion and tissue dynamics in the skin

Award Number: R37AR027883

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: 12/01/1980

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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