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Forward genetic analysis of biliary system formation

Award Number: R01DK103637
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/25/2015
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Forward genetic analysis of biliary system formation - PROJECT SUMMARY Malformation of the biliary system could lead to cholestatic liver diseases, including biliary atresia, the most common infantile liver disease. A developmental anomaly of the biliary system could lead to biliary atresia and other cholestatic liver diseases. To understand the genetic factors that contribute to the pathogenesis of biliary atresia, we undertook a forward genetic screen to identify previously unappreciated genes and pathways responsible for biliary system formation in zebrafish. We have successfully established new 24 zebrafish mutants, which specifically affect the biliary system. We will investigate the molecular mechanisms underlying biliary system phenotypes in zebrafish by using our innovative computational algorithms to quantify subtle differences in three-dimensional biliary branching patterns and utilize machine-learning-based algorithms to characterize their phenotypes unbiasedly. Building on this work, we will extend our studies to human biliary atresia and other biliary system disease patient samples to investigate the pathology. Successful execution of this collaborative scientific endeavor promises to develop important new scientific insights into biliary system formation. It may have profound implications for our understanding of the pathology of biliary system diseases.


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 = $0 )
2026	2025	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	2/4/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $354,200 )
2025	2025	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	4/25/2025	NON-COMPETING CONTINUATION	$354,200
														Subtotal = $354,200

Issue Date FY: 2024 ( Subtotal = $340,032 )
2024	2024	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	5/23/2024	NON-COMPETING CONTINUATION	$340,032
														Subtotal = $340,032

Issue Date FY: 2023 ( Subtotal = $354,200 )
2023	2023	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	5/26/2023	NON-COMPETING CONTINUATION	$354,200
														Subtotal = $354,200

Issue Date FY: 2022 ( Subtotal = $354,200 )
2022	2022	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	6	4/28/2022	COMPETING CONTINUATION	$354,200
2022	2019	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	12/1/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $354,200

Issue Date FY: 2019 ( Subtotal = $356,625 )
2019	2019	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	6/20/2019	NON-COMPETING CONTINUATION	$356,625
														Subtotal = $356,625

Issue Date FY: 2018 ( Subtotal = $356,625 )
2018	2018	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	6/19/2018	NON-COMPETING CONTINUATION	$356,625
														Subtotal = $356,625

Issue Date FY: 2017 ( Subtotal = $356,625 )
2017	2017	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	6/27/2017	NON-COMPETING CONTINUATION	$356,625
														Subtotal = $356,625

Issue Date FY: 2016 ( Subtotal = $356,625 )
2016	2016	CWRU-CLEVELAND CLINIC LERNER COLLEGE	9500 EUCLID AVENUE	CLEVELAND	OH	44195	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	6/22/2016	NON-COMPETING CONTINUATION	$356,625
														Subtotal = $356,625

Issue Date FY: 2015 ( Subtotal = $356,625 )
2015	2015	CWRU-CLEVELAND CLINIC LERNER COLLEGE	9500 EUCLID AVENUE	CLEVELAND	OH	44195	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	7/23/2015	NEW	$356,625
														Subtotal = $356,625

Grand Total All Awards = $3,185,757

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Forward genetic analysis of biliary system formation

Award Number: R01DK103637

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/25/2015

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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