Wednesday, July 2, 2025 7/2/2025

REGULATORS OF EPIDERMAL GENE EXPRESSION

Award Number: R01AR045192
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: 02/27/1999
PERIOD OF PERFORMANCE END DATE: 11/30/2029

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REGULATORS OF EPIDERMAL GENE EXPRESSION - REGULATORS OF EPIDERMAL GENE EXPRESSION PROJECT SUMMARY Epidermal homeostasis is critical for skin barrier function and is disrupted in diseases such as psoriasis, atopic dermatitis, and skin cancer. During the current funding cycle, AR045192 identified new essential roles for specific heterogeneous nuclear ribonucleoproteins (HNRNPs) and ubiquitin- like proteins (UBLs) in epidermal homeostasis. These regulators can exert post-transcriptional and post-translational impacts, respectively, however their actions in the skin are poorly understood. This competing renewal will define how these newly uncovered HNRNPs and UBLs mediate opposing effects on epidermal growth and differentiation. For HNRNP RNA-binding proteins (RBPs), AR045192 knocked out all 33 HNRNPs to uncover new roles for HNRNPC and HNRNPU (pro-progenitor) as well as HNRPNH (pro-differentiation) in epidermal gene expression. HNRNPs exert diverse impacts across RNA lifecycles, however, their actions in epidermis are understudied. AR045192 therefore used non-isotopic ligation-based UV crosslinking immunoprecipitation-mass spectrometry to uncover dynamic assemblies of proteins on mRNAs adjacent to HNRNPC that cooperate with HNRNPC in progenitor mRNA surveillance. Aim I will further define the identity, assembly dependencies, and functions of proteins co-assembled on progenitor and differentiation mRNAs with HNRNPU, and HNRNPH to address the emergent model that specific HNRNPs assemble with distinct combinations of other RBPs on discrete sets of target RNAs to control epidermal homeostasis Conjugation to UBLs, including ubiquitin, NEDD8, and SUMO2, can alter a protein’s localization, interactions, stability, and function, however, roles for UBLs in epidermal homeostasis are not fully characterized. AR045192 knocked out 124 genes encoding all human UBLs, and the enzymes that conjugate them to their target proteins to uncover opposing UBL actions in epidermis. The NEDD8 UBL, along with its corresponding NAE1 and UBA3 enzyme subunits, was essential to maintain undifferentiated progenitor gene expression in human and mouse epidermal cells and tissues. In contrast, the SUMO2 UBL, along with its SAE1 and UBA2 enzyme subunits, was required for differentiation. HNRNPU was identified as NEDD8-tagged in undifferentiated keratinocytes and SUMO2-tagged in differentiating cells; disrupting this reciprocal tagging altered HNRNPU-bound target RNAs. Aim II will apply new methods to characterize the opposing actions of NEDD8 and SUMO2 UBLs in epidermal gene regulation. This effort will expand insight into how specific HNRNP and UBL regulators exert their newly identified essential impacts on epidermal gene expression.


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 = $555,735 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	26	1/17/2025	COMPETING CONTINUATION	$557,140
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	26	5/1/2025	COMPETING CONTINUATION	-$1,405
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	004	26	5/19/2025	COMPETING CONTINUATION	$8
2025	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	25	1/9/2025	NON-COMPETING CONTINUATION	$0
2025	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	25	5/19/2025	NON-COMPETING CONTINUATION	-$8
														Subtotal = $555,735

Issue Date FY: 2024 ( Subtotal = $437,661 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	25	11/3/2023	NON-COMPETING CONTINUATION	$406,078
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	25	6/7/2024	NON-COMPETING CONTINUATION	$31,583
														Subtotal = $437,661

Issue Date FY: 2023 ( Subtotal = $452,436 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	24	2/15/2023	NON-COMPETING CONTINUATION	$45,243
2023	2023	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	24	11/18/2022	NON-COMPETING CONTINUATION	$407,193
														Subtotal = $452,436

Issue Date FY: 2022 ( Subtotal = $463,137 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	23	5/4/2022	NON-COMPETING CONTINUATION	$42,103
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	23	1/6/2022	NON-COMPETING CONTINUATION	$421,034
														Subtotal = $463,137

Issue Date FY: 2021 ( Subtotal = $459,691 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	22	12/11/2020	NON-COMPETING CONTINUATION	$426,519
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	22	5/17/2021	NON-COMPETING CONTINUATION	$33,172
														Subtotal = $459,691

Issue Date FY: 2020 ( Subtotal = $504,604 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	21	6/26/2020	COMPETING CONTINUATION	$52,695
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	21	2/14/2020	COMPETING CONTINUATION	$504,604
2020	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	20	2/6/2020	NON-COMPETING CONTINUATION	$0
2020	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	20	6/26/2020	NON-COMPETING CONTINUATION	-$52,695
														Subtotal = $504,604

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	20	5/6/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $354,617 )
2018	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	20	6/18/2018	NON-COMPETING CONTINUATION	$354,617
														Subtotal = $354,617

Issue Date FY: 2017 ( Subtotal = $353,926 )
2017	2017	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	19	6/2/2017	NON-COMPETING CONTINUATION	$353,926
														Subtotal = $353,926

Issue Date FY: 2016 ( Subtotal = $353,246 )
2016	2016	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	18	6/13/2016	NON-COMPETING CONTINUATION	$353,246
														Subtotal = $353,246

Issue Date FY: 2015 ( Subtotal = $352,610 )
2015	2015	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	17	5/6/2015	NON-COMPETING CONTINUATION	$352,610
														Subtotal = $352,610

Issue Date FY: 2014 ( Subtotal = $351,670 )
2014	2014	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	16	7/17/2014	COMPETING CONTINUATION	$351,670
														Subtotal = $351,670

Issue Date FY: 2013 ( Subtotal = $403,274 )
2013	2013	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	15	7/15/2013	NON-COMPETING CONTINUATION	$21,226
2013	2013	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	15	4/19/2013	NON-COMPETING CONTINUATION	$382,048
														Subtotal = $403,274

Issue Date FY: 2012 ( Subtotal = $428,510 )
2012	2012	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	14	4/30/2012	NON-COMPETING CONTINUATION	$340,590
2012	2012	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	14	5/28/2012	SUPPLEMENT FOR EXPANSION	$87,920
														Subtotal = $428,510

Issue Date FY: 2011 ( Subtotal = $339,467 )
2011	2011	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	13	4/8/2011	NON-COMPETING CONTINUATION	$318,250
2011	2011	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	13	6/8/2011	NON-COMPETING CONTINUATION	$21,217
														Subtotal = $339,467

Issue Date FY: 2010 ( Subtotal = $352,485 )
2010	2010	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	12	4/26/2010	NON-COMPETING CONTINUATION	$352,485
														Subtotal = $352,485

Issue Date FY: 2009 ( Subtotal = $354,911 )
2009	2009	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	11	6/9/2009	COMPETING CONTINUATION	$354,911
														Subtotal = $354,911

Issue Date FY: 2008 ( Subtotal = $337,512 )
2008	2008	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	10	2/6/2008	NON-COMPETING CONTINUATION	$337,512
														Subtotal = $337,512

Grand Total All Awards = $9,592,357

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REGULATORS OF EPIDERMAL GENE EXPRESSION

Award Number: R01AR045192

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: 02/27/1999

PERIOD OF PERFORMANCE END DATE: 11/30/2029

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