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High resolution 3D mapping of cellular heterogeneity within multiple types of mineralized tissues

Award Number: U54AR078664
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/21/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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High resolution 3D mapping of cellular heterogeneity within multiple types of mineralized tissues - Overall Abstract: The goal of the HuBMAP program is to appreciate the unique contextual role of individual cells within the 3D structure of a tissue at its most basic level of transcriptional activity, cellular signaling and cellular response. To date the subject tissues have not included the mineralized skeletal system due to technical issues that preclude the requirements of the HuBMAP program. We have solved those issues with a protocol that is capable of performing multimodal histology that include methods for advanced and repetitive in situ hybridization. We will develop this technology for three very different mineralized skeletal tissues: tooth, trabecular bone and cartilage structures of the knee. The Coordination Core will acquire the three tissue types from de-identified human sources. Each sample will be oriented to its source tissue, imaged by µCT to capture its mineral structure and processed into a histological stack to create a 3D representation of the tissue. Using the histological stack, the Mineralized Tissue Program will perform both in situ hybridization to identify the multiple cell types and seqFISH hybridization to capture the cell transcriptome of the identified cell types. These technically demanding steps will require direction from established HuBMAP investigators as well as UConn faculty who are experts in high resolution confocal microscopy. The Data Analysis Core will translate the image files generated by these techniques into 3D cellular maps of the target tissue and transcriptome composition of each cell type. From those data files, our contextual molecular mapping program, TOPAS, will examine the transcriptional and signaling pathways to impute how neighboring cells coordinate their activities to respond to mechanical loading and systemic factors that regulate skeletal health. The workflow and analytical platforms that we developed for the skeletal system will be aligned with the requirement of the HIVE including an outreach initiative. First, we will provide opportunities to transfer the histological technology to major academic skeletal research groups. Second, once our skeletal data becomes available from the central HIVE source, we will develop virtual workshops to inform the skeletal biology community of this valuable resource and how it can be utilized to unravel rare diseases affecting the skeleton. HuBMAP will be a transformational technology that every tissue centric group needs to incorporate. Our role is to ensure that the skeletal biology community is included in this new experimental platform, and that it is employed to solve the major genetic and therapeutic challenges affecting skeletal health.


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 = -$235 )
2026	2023	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Trans-NIH Research Support	000	4	12/11/2025	NON-COMPETING CONTINUATION	-$235
														Subtotal = -$235

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Trans-NIH Research Support	000	4	11/27/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Trans-NIH Research Support	000	4	7/15/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $634,537 )
2023	2023	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Trans-NIH Research Support	005	4	7/26/2023	NON-COMPETING CONTINUATION	$534,537
2023	2023	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Trans-NIH Research Support	006	4	9/11/2023	SUPPLEMENT FOR EXPANSION	$100,000
2023	2022	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Trans-NIH Research Support	004	3	5/3/2023	EXTENSION WITH OR WITHOUT FUNDS	$0
2023	2022	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Trans-NIH Research Support	003	3	5/1/2023	EXTENSION WITH OR WITHOUT FUNDS	$278,018
2023	2021	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Trans-NIH Research Support	001	2	5/1/2023	SUPPLEMENT FOR EXPANSION	-$33,913
2023	2021	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Trans-NIH Research Support	002	2	5/1/2023	SUPPLEMENT FOR EXPANSION	-$87,328
2023	2021	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Trans-NIH Research Support	000	2	5/1/2023	NON-COMPETING CONTINUATION	-$156,777
														Subtotal = $634,537

Issue Date FY: 2022 ( Subtotal = $535,000 )
2022	2022	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Trans-NIH Research Support	003	3	9/15/2022	EXTENSION WITH OR WITHOUT FUNDS	$535,000
2022	2021	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Trans-NIH Research Support	000	2	4/20/2022	NON-COMPETING CONTINUATION	$0
2022	2021	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Trans-NIH Research Support	002	2	9/14/2022	NON-COMPETING CONTINUATION	$0
2022	2021	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Trans-NIH Research Support	001	2	5/2/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $535,000

Issue Date FY: 2021 ( Subtotal = $819,803 )
2021	2021	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Trans-NIH Research Support	001	2	8/30/2021	SUPPLEMENT FOR EXPANSION	$100,000
2021	2021	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Trans-NIH Research Support	000	2	8/20/2021	NON-COMPETING CONTINUATION	$462,295
2021	2021	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Trans-NIH Research Support	002	2	9/7/2021	SUPPLEMENT FOR EXPANSION	$257,508
														Subtotal = $819,803

Issue Date FY: 2020 ( Subtotal = $507,705 )
2020	2020	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Trans-NIH Research Support	000	1	9/21/2020	NEW	$507,705
														Subtotal = $507,705

Grand Total All Awards = $2,496,810

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High resolution 3D mapping of cellular heterogeneity within multiple types of mineralized tissues

Award Number: U54AR078664

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/21/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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