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3D biomimetic lymph node engineered extracellular vesicles for understanding the heterogeneity of adaptive immunity

Award Number: R35GM133794
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ABSTRACT Understanding how immune-heterogeneity leverages cellular diversity to achieve the adaptivity and flexibility in immune-responses is a core challenge that has not been well studied, largely due to the lack of a valid immunity tissue model for investigation of cellular communications. Recent discovery of trafficking vesicles since 2013 Nobel Prize of Medicine shined the light on the new avenue for understanding long-distance, non-contact cellular communications in modulating immunity. However, the study of such diverse and nano-sized vesicles, namely exosomes, is extremely challenging, due to immense difficulties in differentiating dynamic and heterogeneous vesicle populations presented in the in vivo system. Our research work addresses key technology gaps by developing a series of tool sets, including high-efficient and high-throughput microfluidic approach for exosome isolation, subtyping, molecular engineering and transfection, and nano-delivery. Recently, we observed that molecular packaging of secreted exosomes is highly variable upon the change of cellular culture environment as well as surrounding community. The in vitro investigations with 2D cell culture systems are incapable of interpreting in vivo exosome immunity modulation mechanism. We hypothesize that a 3D biomimetic lymph node tissue system could serve as the in vivo -like tissue model for effectively studying in vivo exosome molecular packaging and secretion dynamics upon stimulations, for interconnecting exosomal cargoes with cellular level responses. This five-year study will focus on three key challenges for precisely elucidating immune-modulation at the molecular level via the exosome route: 1) Develop a 3D, programmable biomimetic lymph node tissue foundry with well-defined immunological adaptations for mimicking in vivo immune tissue microenvironment; 2) Develop a single cell single exosome study approach for highly sensitive detection and subtyping of single exosome populations with dynamic and statistical significance for understanding immunity heterogeneity; 3) Discover motifs that can selectively pack immuno-stimulating microRNAs, as well as the MHC-binding peptides into exosomes for targeted immunity modulation, which can establish the interconnection of cargo internalization with cellular level responses. The long-term goal is to advance our understanding in immunity regulation heterogeneity and eventually be able to precisely programme immune responses at the molecular precision.


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 = $411,881 )
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	001	5	7/31/2023	NON-COMPETING CONTINUATION	$381,250
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	000	4	5/24/2023	SUPPLEMENT FOR EXPANSION	$7,595
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	002	5	8/2/2023	SUPPLEMENT FOR EXPANSION	$23,036
														Subtotal = $411,881

Issue Date FY: 2022 ( Subtotal = $496,426 )
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	001	4	7/25/2022	NON-COMPETING CONTINUATION	$381,250
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	000	3	11/12/2021	SUPPLEMENT FOR EXPANSION	$46,070
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	002	4	8/10/2022	SUPPLEMENT FOR EXPANSION	$69,106
														Subtotal = $496,426

Issue Date FY: 2021 ( Subtotal = $516,650 )
2021	2021	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	004	3	8/24/2021	SUPPLEMENT FOR EXPANSION	$135,400
2021	2021	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	003	3	7/27/2021	NON-COMPETING CONTINUATION	$381,250
2021	2020	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	001	2	2/6/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$47,998
2021	2020	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	002	2	7/26/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2021	2019	UNIVERSITY OF KANSAS CENTER FOR RESEARCH, INC.	2385 IRVING HILL RD	LAWRENCE	KS	66045	DOUGLAS	USA	Biomedical Research and Research Training	000	1	2/6/2021	NEW	-$47,998
														Subtotal = $516,650

Issue Date FY: 2020 ( Subtotal = $381,250 )
2020	2020	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	001	2	9/23/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$381,250
2020	2019	UNIVERSITY OF KANSAS CENTER FOR RESEARCH, INC.	2385 IRVING HILL RD	LAWRENCE	KS	66045	DOUGLAS	USA	Biomedical Research and Research Training	000	1	9/17/2020	NEW	$0
														Subtotal = $381,250

Issue Date FY: 2019 ( Subtotal = $378,750 )
2019	2019	UNIVERSITY OF KANSAS CENTER FOR RESEARCH, INC.	2385 IRVING HILL RD	LAWRENCE	KS	66045	DOUGLAS	USA	Biomedical Research and Research Training	000	1	9/16/2019	NEW	$378,750
														Subtotal = $378,750

Grand Total All Awards = $2,184,957

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3D biomimetic lymph node engineered extracellular vesicles for understanding the heterogeneity of adaptive immunity

Award Number: R35GM133794

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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