Tuesday, July 1, 2025 7/1/2025

Extracellular Vesicle-mediated islet immune cross talk in Type 1 Diabetes pathogenesis

Award Number: R01DK133885
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: 09/15/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Extracellular Vesicle-mediated islet immune cross talk in Type 1 Diabetes pathogenesis - PROJECT SUMMARY/ABSTRACT (30 lines or less) The premise for the proposed research stems from precedence in other diseases, such as cancer, cardiovascular, neurodegenerative, and most relevant to the current proposal, autoimmune diseases, in which extracellular vesicles (EVs) play a role in the pathophysiology and are important biomarkers for early detection. However, in human type 1 diabetes (T1D), little is known concerning EVs in cellular communication. Our overall hypothesis is that autocrine-paracrine interactions, mediated through EVs, between the islets and islet-infiltrating immune cells in the pancreas contribute to the development and progression of T1D. Our specific aims are: 1) to assess the functional impact of islet-infiltrating T-cell derived EVs (T-EV) from T1D and autoantibody+ (Aab+) donors on islet health and on distinct immune cell populations; 2) to investigate the contribution of stressed or T1D islet-derived EVs (I-EV) on immune cell phenotype and islet health; and 3) to decipher the differential protein cargo in T-EV and I-EV from T1D and Aab+ donors. To address these aims, we have assembled a team of investigators with highly relevant expertise, techniques and unique resources of cell lines and tissue samples. From 36 human tissue donors with T1D or Aab positivity, we have >600 T cell lines grown directly from the individual islets of pancreata. We have the expertise and technical ability to isolate EV from islets (I-EV) and from islet-infiltrating T cell lines (T-EV) from T1D donors. Our preliminary data indicates I-EV and T-EV have both paracrine and autocrine effects on islet health and immune cell phenotype. Our Research Plan is to generate T-EV and I-EV from donors with T1D of distinct durations or positivity for islet autoantibodies, to evaluate their effects on islet health and immune cell function, and to determine the uniquely packaged protein cargo from these EVs whose molecular composition reflects the pathophysiologic state of the disseminating cell. These studies will yield important information concerning the communication between immune cell populations and islets via EVs in the pathogenesis of T1D, and potential biomarkers or therapeutic targets for T1D.


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 = $747,900 )
2025	2025	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	5/30/2025	NON-COMPETING CONTINUATION	$747,900
														Subtotal = $747,900

Issue Date FY: 2024 ( Subtotal = $751,132 )
2024	2024	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	5/7/2024	NON-COMPETING CONTINUATION	$751,132
														Subtotal = $751,132

Issue Date FY: 2023 ( Subtotal = $751,132 )
2023	2023	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/28/2023	NON-COMPETING CONTINUATION	$751,132
														Subtotal = $751,132

Issue Date FY: 2022 ( Subtotal = $770,132 )
2022	2022	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/12/2022	NEW	$770,132
														Subtotal = $770,132

Grand Total All Awards = $3,020,296

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Extracellular Vesicle-mediated islet immune cross talk in Type 1 Diabetes pathogenesis

Award Number: R01DK133885

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: 09/15/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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