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Probing Tissue Heterogeneity and Stem Cell Niche with Micro-Organospheres

Award Number: R35GM122465
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2017
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Probing Tissue Heterogeneity and Stem Cell Niche with Micro-Organospheres - Abstract Stem cells self-renew and differentiate into various cell lineages to sustain tissue homeostasis and functions. Most tissue microenvironments comprise multiple components, including epithelial, stromal, immune, and endothelial cells, that interact with each other to coordinate response to intrinsic and extrinsic stimuli. There remains an unmet need for in vitro models that can capture tissue heterogeneity and enable high-throughput studies. The PI developed Micro-OrganoSpheres (MOS) that can be established rapidly and efficiently from small amounts of primary tissues. Allowing self-renewal and differentiation of adult stem cells to recapitulate key tissue characteristics, MOS also sustain the original tissue microenvironment, enabling both ultra-high-throughput assays aided by deep-learning algorithms and direct microbial-host interactions. For the next R35 period, MOS will be leveraged as a fundamental research tool for understanding interactive processes in heterogeneous tissues in a systematic and scalable manner. Three projects are proposed: (1) We will set up a high-throughput MOS screen to systematically study how different cell types in a heterogenous tissue respond to different microbes. (2) We will develop a MOS combinatorial indexing technique to probe how cell-cell interactions in local microenvironments lead to spatially heterogenous tissue responses. (3) We will use MOS engraftment and intravital imaging to understand cell fate decisions and progression of stem cell niche from development to adulthood. The success of these projects will elucidate the mechanisms by which 1) different cells coordinate locally to respond to stimuli and 2) the stem cell niche progresses during growth. Furthermore, this research will provide the broader scientific community with basic research techniques that can be generalized to understand a wide variety of tissue and stem cell functions.


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 = $681,990 )
2025	2025	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	21100 ERWIN ST	WOODLAND HILLS	CA	91367	LOS ANGELES	USA	Biomedical Research and Research Training	002	9	8/7/2025	NON-COMPETING CONTINUATION	$681,990
2025	2024	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	21100 ERWIN ST	WOODLAND HILLS	CA	91367	LOS ANGELES	USA	Biomedical Research and Research Training	000	8	11/6/2024	NON-COMPETING CONTINUATION	$0
2025	2021	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	21100 ERWIN ST	WOODLAND HILLS	CA	91367	LOS ANGELES	USA	Biomedical Research and Research Training	001	6	1/15/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $681,990

Issue Date FY: 2024 ( Subtotal = $681,990 )
2024	2024	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	21100 ERWIN ST	WOODLAND HILLS	CA	91367	LOS ANGELES	USA	Biomedical Research and Research Training	000	8	9/6/2024	NON-COMPETING CONTINUATION	$681,990
														Subtotal = $681,990

Issue Date FY: 2023 ( Subtotal = $681,990 )
2023	2023	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	1018 WESTWOOD BLVD	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	7	8/15/2023	COMPETING CONTINUATION	$681,990
														Subtotal = $681,990

Issue Date FY: 2022 ( Subtotal = $36,084 )
2022	2021	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	1018 WESTWOOD BLVD	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	001	6	2/22/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$205,032
2022	2021	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Biomedical Research and Research Training	002	5	8/28/2022	NON-COMPETING CONTINUATION	-$2
2022	2021	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	1018 WESTWOOD BLVD	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	003	6	8/28/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$2
2022	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	5	2/21/2022	NON-COMPETING CONTINUATION	-$168,948
														Subtotal = $36,084

Issue Date FY: 2021 ( Subtotal = $535,194 )
2021	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	5	3/26/2021	NON-COMPETING CONTINUATION	$535,194
														Subtotal = $535,194

Issue Date FY: 2020 ( Subtotal = $674,454 )
2020	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	4	4/2/2020	NON-COMPETING CONTINUATION	$566,644
2020	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	001	4	9/3/2020	SUPPLEMENT FOR EXPANSION	$107,810
														Subtotal = $674,454

Issue Date FY: 2019 ( Subtotal = $734,277 )
2019	2019	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	3	3/26/2019	NON-COMPETING CONTINUATION	$610,555
2019	2019	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	001	3	7/19/2019	SUPPLEMENT FOR EXPANSION	$123,722
														Subtotal = $734,277

Issue Date FY: 2018 ( Subtotal = $578,016 )
2018	2018	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	002	2	9/19/2018	SUPPLEMENT FOR EXPANSION	$42,822
2018	2018	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	001	2	5/24/2018	NON-COMPETING CONTINUATION	$53,520
2018	2018	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	2	3/29/2018	NON-COMPETING CONTINUATION	$481,674
														Subtotal = $578,016

Issue Date FY: 2017 ( Subtotal = $282,681 )
2017	2017	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	1	3/24/2017	NEW	$282,681
														Subtotal = $282,681

Grand Total All Awards = $4,886,676

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Probing Tissue Heterogeneity and Stem Cell Niche with Micro-Organospheres

Award Number: R35GM122465

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2017

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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