Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Developmental Mechanisms of Human Idiopathic Scoliosis

Award Number: P01HD084387
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2016
PERIOD OF PERFORMANCE END DATE: 05/31/2027

Group Awards By:

View Award Description

Developmental Mechanisms of Human Idiopathic Scoliosis - Project Summary/Abstract (Overall) Adolescent idiopathic scoliosis (AIS) is a twisting condition of the spine and is the most common pediatric musculoskeletal disorder, affecting 3% of children worldwide. Children with AIS risk severe disfigurement, back pain, and physiologic dysfunction later in life. Girls requiring treatment for AIS outnumber boys by more than five-fold, for reasons that are unknown. Hospital charges for AIS surpass one billion dollars annually in the U.S. and are rising significantly faster than for other pediatric procedures. AIS is treated symptomatically rather than preventively because the underlying etiology has been poorly understood. Genetic contributions to AIS are significant, but few human susceptibility loci were identified prior to the beginning of this Program. The mechanisms driven by these loci were likewise largely unknown, as they mapped within non-coding genomic regions that were not easily interpreted. The AIS field also lacked appropriate animal models that enable mechanistic and therapeutic studies. To address these issues, we established an innovative collaborative approach combining three Projects to lead unbiased gene discovery in humans, modeling and gene discovery in zebrafish, and genomic analysis of postnatal spine development. Our program addressed six gaps in knowledge: (i) identity of the tissue and cellular origins of AIS; (ii) defining the true beginning of AIS disease pathogenesis; (iii) defining the genetic factors and genetic interactions underlying AIS; (iv) developing robust vertebrate systems to functionally validate, interpret, and model human genetic findings; (v) defining the molecular mechanisms controlling spinal development post-somitogenesis, and the correlation with AIS; (vi) defining the basis of sexual dimorphism in AIS. In the prior award cycle our Program significantly advanced each of these initiatives. Integrating data in humans and animal models, our data underscored cartilage as a functional tissue in AIS and specifically highlighted the extracellular matrix compartment, new paradigms in the field. Our Program discovered several new AIS genetic susceptibility loci in human and developed 73 new zebrafish models of spine deformity. Data from each Project also converged on the hypomorphic nature of AIS disease alleles, supporting multigenic inheritance. We defined the non-coding regulatory landscape of human and mouse AIS-related tissues, and discovered that knockout of one such regulator linked to female AIS in humans produces a female-biased phenotype in mouse. Here we propose a comprehensive plan to drive these discoveries forward to define AIS disease mechanisms using genetically targeted mouse and zebrafish models, to define cell-specific transcriptional, epigenetic, and signaling mechanisms underlying AIS, to continue identifying vertebrate models of spine deformity by forward genetic screens in mouse and zebrafish, and to discover new high-risk alleles contributing to AIS in patients refractory to treatment. We will also expand our investigations to address why AIS has a female bias, and to testing rationally selected drug therapies in vertebrate models. These studies will advance fundamental understanding of AIS, inform diagnosis and highlight potential therapeutic targets.


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 = $1,285,873 )
2025	2025	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Child Health and Human Development Extramural Research	000	9	6/11/2025	NON-COMPETING CONTINUATION	$1,285,873
														Subtotal = $1,285,873

Issue Date FY: 2024 ( Subtotal = $1,272,978 )
2024	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Child Health and Human Development Extramural Research	000	8	6/19/2024	NON-COMPETING CONTINUATION	$1,272,978
														Subtotal = $1,272,978

Issue Date FY: 2023 ( Subtotal = $1,358,310 )
2023	2023	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Child Health and Human Development Extramural Research	002	7	6/8/2023	NON-COMPETING CONTINUATION	$1,358,310
2023	2022	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Child Health and Human Development Extramural Research	001	6	6/1/2023	COMPETING CONTINUATION	$120,291
2023	2020	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Child Health and Human Development Extramural Research	000	5	6/1/2023	NON-COMPETING CONTINUATION	-$120,291
														Subtotal = $1,358,310

Issue Date FY: 2022 ( Subtotal = $1,427,879 )
2022	2022	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Child Health and Human Development Extramural Research	001	6	6/15/2022	COMPETING CONTINUATION	$1,427,879
2022	2020	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Child Health and Human Development Extramural Research	000	5	6/3/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,427,879

Issue Date FY: 2020 ( Subtotal = $1,123,586 )
2020	2020	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Child Health and Human Development Extramural Research	000	5	6/27/2020	NON-COMPETING CONTINUATION	$1,123,586
														Subtotal = $1,123,586

Issue Date FY: 2019 ( Subtotal = $1,123,586 )
2019	2019	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Child Health and Human Development Extramural Research	001	4	7/6/2019	NON-COMPETING CONTINUATION	$1,123,586
2019	2018	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Child Health and Human Development Extramural Research	000	3	11/14/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,123,586

Issue Date FY: 2018 ( Subtotal = $1,233,261 )
2018	2018	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Child Health and Human Development Extramural Research	000	3	9/1/2018	NON-COMPETING CONTINUATION	$1,233,261
														Subtotal = $1,233,261

Issue Date FY: 2017 ( Subtotal = $1,287,111 )
2017	2017	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Child Health and Human Development Extramural Research	000	2	7/27/2017	NON-COMPETING CONTINUATION	$1,287,111
														Subtotal = $1,287,111

Issue Date FY: 2016 ( Subtotal = $1,545,569 )
2016	2016	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Child Health and Human Development Extramural Research	000	1	8/21/2016	NEW	$1,545,569
														Subtotal = $1,545,569

Grand Total All Awards = $11,658,153

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Developmental Mechanisms of Human Idiopathic Scoliosis

Award Number: P01HD084387

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2016

PERIOD OF PERFORMANCE END DATE: 05/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer