Thursday, November 21, 2024 11/21/2024

MECHANISMS OF DESMOSOME REGULATION IN SKIN DISEASE

Award Number: R01AR048266
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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View Award Abstract

Desmosomes are adhesive intercellular junctions that play critical roles in epidermal homeostasis by mediating robust cell-cell adhesion and by modulating signaling pathways that regulate epidermal differentiation. The importance of desmosomes is highlighted by numerous autoimmune and inherited skin diseases that compromise desmosome function and cause epidermal fragility. These diseases include pemphigus vulgaris (PV), a severe autoimmune epidermal blistering disease caused by autoantibodies (IgG) directed against the desmosomal cadherin desmoglein-3 (Dsg3), and severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome caused by DSG1 loss of function mutations. Our previous studies of PV revealed that desmosomal proteins are associated with lipid rafts, and our recent findings indicate that a mutation in the Dsg1TMD that abrogates lipid raft association, compromises desmosome formation, and causes SAM syndrome. Lipid rafts are important for a variety of cellular functions, including signaling, endocytosis and membrane domain formation. The important role of lipid rafts in regulating Dsg function in different skin diseases underscores the importance of Dsg association with lipid rafts in normal desmosome function and epidermal homeostasis. We hypothesize that Dsg association with rafts is required for desmosome assembly, segregation from adherens junctions, and for Dsg adhesive and signaling activities necessary for epidermal homeostasis. The experiments outlined in this proposal are designed to reveal the raft targeting features of desmosomal cadherins, how raft association regulates desmosome and adherens junction membrane domain formation, and how loss of Dsg raft association leads to SAM syndrome. The outcome of these studies will produce fundamentally new conceptual models for desmosome regulation and will form a foundation for the treatment of skin diseases associated with loss of desmosome function.


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 = $442,244 )
2024	2024	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	20	6/12/2024	NON-COMPETING CONTINUATION	$31,913
2024	2024	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	20	4/10/2024	NON-COMPETING CONTINUATION	$410,331
														Subtotal = $442,244

Issue Date FY: 2023 ( Subtotal = $455,950 )
2023	2023	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	19	3/15/2023	NON-COMPETING CONTINUATION	$455,950
														Subtotal = $455,950

Issue Date FY: 2022 ( Subtotal = $456,436 )
2022	2022	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	18	4/28/2022	NON-COMPETING CONTINUATION	$456,436
														Subtotal = $456,436

Issue Date FY: 2021 ( Subtotal = $448,741 )
2021	2021	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	17	2/26/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$416,359
2021	2021	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	004	17	6/29/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$32,382
2021	2021	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	17	5/25/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$281,548
2021	2020	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	16	5/25/2021	COMPETING CONTINUATION	-$281,548
2021	2020	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	16	2/25/2021	COMPETING CONTINUATION	$0
														Subtotal = $448,741

Issue Date FY: 2020 ( Subtotal = $476,321 )
2020	2020	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	16	7/21/2020	COMPETING CONTINUATION	$35,634
2020	2020	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	16	3/9/2020	COMPETING CONTINUATION	$476,321
2020	2018	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	15	7/21/2020	NON-COMPETING CONTINUATION	-$35,634
														Subtotal = $476,321

Issue Date FY: 2018 ( Subtotal = $504,519 )
2018	2018	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	15	4/17/2018	NON-COMPETING CONTINUATION	$504,519
														Subtotal = $504,519

Issue Date FY: 2017 ( Subtotal = $504,519 )
2017	2017	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	14	3/27/2017	NON-COMPETING CONTINUATION	$454,067
2017	2017	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	14	6/14/2017	NON-COMPETING CONTINUATION	$50,452
														Subtotal = $504,519

Issue Date FY: 2016 ( Subtotal = $480,491 )
2016	2016	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	13	3/17/2016	NON-COMPETING CONTINUATION	$444,660
2016	2016	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	13	9/19/2016	SUPPLEMENT FOR EXPANSION	$35,831
														Subtotal = $480,491

Issue Date FY: 2015 ( Subtotal = $444,660 )
2015	2015	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	12	3/25/2015	NON-COMPETING CONTINUATION	$444,660
														Subtotal = $444,660

Issue Date FY: 2014 ( Subtotal = $459,075 )
2014	2014	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	11	9/16/2014	COMPETING CONTINUATION	-$459,075
2014	2014	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	11	3/27/2014	COMPETING CONTINUATION	$459,075
2014	2014	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	006	11	9/19/2014	COMPETING CONTINUATION	$459,075
2014	2012	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	10	9/16/2014	NON-COMPETING CONTINUATION	-$324,086
2014	2012	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	007	10	9/19/2014	NON-COMPETING CONTINUATION	$324,086
2014	2012	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	10	3/25/2014	NON-COMPETING CONTINUATION	$0
2014	2011	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	005	9	9/16/2014	NON-COMPETING CONTINUATION	-$324,086
2014	2011	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	008	9	9/19/2014	NON-COMPETING CONTINUATION	$324,086
2014	2010	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	009	8	9/19/2014	NON-COMPETING CONTINUATION	$337,590
2014	2010	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	004	8	9/16/2014	NON-COMPETING CONTINUATION	-$337,590
														Subtotal = $459,075

Issue Date FY: 2012 ( Subtotal = $324,086 )
2012	2012	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	10	7/13/2012	NON-COMPETING CONTINUATION	$324,086
														Subtotal = $324,086

Issue Date FY: 2011 ( Subtotal = $324,086 )
2011	2011	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	9	7/15/2011	NON-COMPETING CONTINUATION	$324,086
														Subtotal = $324,086

Issue Date FY: 2010 ( Subtotal = $337,590 )
2010	2010	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	8	7/22/2010	NON-COMPETING CONTINUATION	$337,590
														Subtotal = $337,590

Issue Date FY: 2009 ( Subtotal = $341,000 )
2009	2009	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	7	7/16/2009	NON-COMPETING CONTINUATION	$341,000
2009	2008	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	8/18/2009	COMPETING CONTINUATION	$0
														Subtotal = $341,000

Issue Date FY: 2008 ( Subtotal = $340,908 )
2008	2008	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	7/31/2008	COMPETING CONTINUATION	$340,908
														Subtotal = $340,908

Issue Date FY: 2006 ( Subtotal = $265,687 ) (Continued on the next page)
Grand Total All Awards = $7,755,747

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MECHANISMS OF DESMOSOME REGULATION IN SKIN DISEASE

Award Number: R01AR048266

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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