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Regulation of intestinal epithelial barrier function by intercellular junction proteins in health and disease

Award Number: R01DK059888
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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View Award Abstract

Abstract Inflammatory bowel diseases are characterized by intestinal inflammation, increased mucosal cytokines and compromised epithelial barrier function. Epithelial barrier function is regulated by intercellular junctions that encompass the tight junction (TJ), adherens junction (AJ) and desmosomes (DMs). It is now evident that intercellular junctions are highly dynamic structures and their component proteins actively participate in regulating epithelial homeostasis. Mucosal inflammation compromises epithelial homeostatic properties thereby resulting in epithelial barrier compromise which contributes to disease pathogenesis. Our knowledge of the molecular basis of intercellular junction protein cross-talk, epithelial homeostasis and compromised barrier in intestinal inflammation is however very limited. Thus the overall goals of this proposal are to identify mechanisms by which intercellular junction proteins control epithelial homeostasis, barrier function and repair after injury in disease. We will specifically investigate the role of two key intercellular junction proteins, claudin23 and desmoglein 2 in regulating the intestinal epithelial barrier function and repair after injury. The influence of inflammatory cytokines on such regulatory processes will be determined. In addition to gaining insights into the molecular basis of intestinal epithelial barrier regulation, these studies will provide new ideas for the development of therapeutic agents that strengthen the intestinal epithelial barrier, promote wound repair and reduce mucosal inflammation. These studies will also provide insight into strategies of transiently perturbing the epithelial barrier for therapeutic drug/vaccine delivery.


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: 2023 ( Subtotal = $547,382 )
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	23	5/23/2023	NON-COMPETING CONTINUATION	$547,382
														Subtotal = $547,382

Issue Date FY: 2022 ( Subtotal = $544,543 )
2022	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	22	5/17/2022	NON-COMPETING CONTINUATION	$544,543
2022	2021	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	21	3/23/2022	COMPETING CONTINUATION	$198,621
2022	2020	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	20	3/23/2022	NON-COMPETING CONTINUATION	-$198,621
														Subtotal = $544,543

Issue Date FY: 2021 ( Subtotal = $544,543 )
2021	2021	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	21	9/23/2021	COMPETING CONTINUATION	$544,543
2021	2020	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	20	9/14/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $544,543

Issue Date FY: 2020 ( Subtotal = $506,774 )
2020	2020	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	20	5/8/2020	NON-COMPETING CONTINUATION	$506,774
														Subtotal = $506,774

Issue Date FY: 2019 ( Subtotal = $506,774 )
2019	2019	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	19	5/7/2019	NON-COMPETING CONTINUATION	$506,774
														Subtotal = $506,774

Issue Date FY: 2018 ( Subtotal = $506,774 )
2018	2018	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	18	4/24/2018	NON-COMPETING CONTINUATION	$506,774
														Subtotal = $506,774

Issue Date FY: 2017 ( Subtotal = $506,774 )
2017	2017	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	17	4/25/2017	NON-COMPETING CONTINUATION	$456,096
2017	2017	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	17	6/16/2017	NON-COMPETING CONTINUATION	$50,678
2017	2016	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	16	2/22/2017	COMPETING CONTINUATION	$367,663
2017	2015	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	15	2/22/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$367,663
														Subtotal = $506,774

Issue Date FY: 2016 ( Subtotal = $506,774 )
2016	2016	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	16	9/22/2016	COMPETING CONTINUATION	$506,774
2016	2015	Regents of the University of Michigan	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	481091287	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	15	9/20/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $506,774

Issue Date FY: 2015 ( Subtotal = $421,312 )
2015	2015	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	15	9/4/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$421,312
2015	2014	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	14	9/3/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $421,312

Issue Date FY: 2014 ( Subtotal = $421,312 )
2014	2014	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	14	7/17/2014	NON-COMPETING CONTINUATION	$421,312
														Subtotal = $421,312

Issue Date FY: 2013 ( Subtotal = $406,565 )
2013	2013	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	13	8/13/2013	NON-COMPETING CONTINUATION	$406,565
														Subtotal = $406,565

Issue Date FY: 2012 ( Subtotal = $421,312 )
2012	2012	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	12	8/31/2012	NON-COMPETING CONTINUATION	$421,312
														Subtotal = $421,312

Issue Date FY: 2011 ( Subtotal = $484,265 )
2011	2011	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	11	8/29/2011	COMPETING CONTINUATION	$484,265
2011	2010	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	8/24/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $484,265

Issue Date FY: 2010 ( Subtotal = $295,478 )
2010	2010	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	8/11/2010	NON-COMPETING CONTINUATION	$295,478
														Subtotal = $295,478

Issue Date FY: 2009 ( Subtotal = $298,463 )
2009	2009	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	8/24/2009	NON-COMPETING CONTINUATION	$298,463
														Subtotal = $298,463

Issue Date FY: 2008 ( Subtotal = $298,463 )
2008	2008	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Digestive Diseases and Nutrition Research	000	8	7/31/2008	NON-COMPETING CONTINUATION	$298,463
														Subtotal = $298,463

Issue Date FY: 2007 ( Subtotal = $304,554 )
2007	2007	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Digestive Diseases and Nutrition Research	000	7	8/9/2007	NON-COMPETING CONTINUATION	$304,554
														Subtotal = $304,554

Issue Date FY: 2006 ( Subtotal = $313,650 )
2006	2006	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Digestive Diseases and Nutrition Research	000	6	8/22/2006	COMPETING CONTINUATION	$313,650
														Subtotal = $313,650

Issue Date FY: 2005 ( Subtotal = $288,800 )
2005	2005	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Digestive Diseases and Nutrition Research	000	5	8/4/2005	NON-COMPETING CONTINUATION	$288,800
														Subtotal = $288,800

Issue Date FY: 2004 ( Subtotal = $288,800 )
2004	2004	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Digestive Diseases and Nutrition Research	000	4	8/18/2004	NON-COMPETING CONTINUATION	$288,800
														Subtotal = $288,800

Issue Date FY: 2003 ( Subtotal = $288,800 ) (Continued on the next page)
Grand Total All Awards = $9,257,756

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Regulation of intestinal epithelial barrier function by intercellular junction proteins in health and disease

Award Number: R01DK059888

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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