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Development and Application of Organelle Chemotype Fingerprinting for the Functional Investigation of Organellar Chloride

Award Number: R35GM147112
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: 08/01/2022
PERIOD OF PERFORMANCE END DATE: 11/03/2025

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Development and Application of Organelle Chemotype Fingerprinting for the Functional Investigation of Organellar Chloride - SUMMARY/ABSTRACT As one of the most abundant anions in the human body, chloride plays a crucial role in human health. Chloride homeostasis is maintained inside the cell while the chloride level is varied based on the function of organelles. Dysregulation of chloride homeostasis caused by the mutation of chloride channels results in various human diseases such as cystic fibrosis (CFTR, >70,000 people worldwide), proteinuria and kidney stones (ClC-5, 39 million people in US), Osteoporosis (ClC-7, 10 million people in US, 43 million people in the risk group). Although five FDA-approved chloride channel modulators have been reported, they only target plasma membrane chloride channels due to the technical barrier. There is no FDA-approved or clinical trial drug that targets organellar chloride channel. The field of chloride channel-targeted therapy is still under-studied (5 FDA-approved drugs, 2 clinical trial) compared to other channels such as calcium, potassium, and sodium. The lack of understanding of the physiological role of organellar chloride and the well-characterized chloride channel are the biggest roadblocks for the development of chloride channel-targeted therapy. Therefore, suitable research tools with a high resolving ability to examine the organelle chloride in live cells is a highly urgent need, which is essential to elucidate the physiological role of organellar chloride and characterize the chloride channel. However, the current chloride measurement with one-dimensional analysis only shows the average ion level. It cannot observe the chloride level change in a minor subset of organelles triggered by the cellular pathway such as STING and autophagy. Furthermore, the typical fluorescence measurement can only tell the variation of the average chloride level (increase, decrease, and no significant change) in certain conditions. The current methods significantly hinder the identification of deactivated cell pathways or protein based on the chloride level measurement. The proposed research integrate organelle selective dual reporters, single organelle measurement, sub- cellular imaging, and the three-dimensional analysis, to fingerprint the chemotype of organelles along with STING pathway, autophagy, and mitochondrial respiration. Completion of the proposed study will find out the physiological role of organellar chloride which shed light on the chloride channel-targeted therapy. The development of the organelle chemotype fingerprinting technique will also provide tools to characterize chloride channels, evaluate chloride channel modulators and identify the deactivated cell pathways or proteins.


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 = $356,907 )
2026	2026	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	002	6	5/22/2026	NON-COMPETING CONTINUATION	$359,260
2026	2025	CLARKSON UNIVERSITY	8 CLARKSON AVE	POTSDAM	NY	13676	SAINT LAWRENCE	USA	Biomedical Research and Research Training	003	4	7/1/2026	NON-COMPETING CONTINUATION	$0
2026	2025	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	001	5	1/21/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$359,260
2026	2025	CLARKSON UNIVERSITY	8 CLARKSON AVE	POTSDAM	NY	13676	SAINT LAWRENCE	USA	Biomedical Research and Research Training	000	4	1/16/2026	NON-COMPETING CONTINUATION	-$361,613
														Subtotal = $356,907

Issue Date FY: 2025 ( Subtotal = $361,614 )
2025	2025	CLARKSON UNIVERSITY	8 CLARKSON AVE	POTSDAM	NY	13676	SAINT LAWRENCE	USA	Biomedical Research and Research Training	000	4	5/26/2025	NON-COMPETING CONTINUATION	$361,614
														Subtotal = $361,614

Issue Date FY: 2024 ( Subtotal = $362,123 )
2024	2024	CLARKSON UNIVERSITY	8 CLARKSON AVE	POTSDAM	NY	13676	SAINT LAWRENCE	USA	Biomedical Research and Research Training	000	3	6/3/2024	NON-COMPETING CONTINUATION	$362,123
														Subtotal = $362,123

Issue Date FY: 2023 ( Subtotal = $663,421 )
2023	2023	CLARKSON UNIVERSITY	8 CLARKSON AVE	POTSDAM	NY	13676	SAINT LAWRENCE	USA	Biomedical Research and Research Training	002	2	8/11/2023	SUPPLEMENT FOR EXPANSION	$290,681
2023	2023	CLARKSON UNIVERSITY	8 CLARKSON AVE	POTSDAM	NY	13676	SAINT LAWRENCE	USA	Biomedical Research and Research Training	001	2	5/16/2023	SUPPLEMENT FOR EXPANSION	$10,121
2023	2023	CLARKSON UNIVERSITY	8 CLARKSON AVE	POTSDAM	NY	13676	SAINT LAWRENCE	USA	Biomedical Research and Research Training	000	2	5/4/2023	NON-COMPETING CONTINUATION	$362,619
														Subtotal = $663,421

Issue Date FY: 2022 ( Subtotal = $363,102 )
2022	2022	CLARKSON UNIVERSITY	8 CLARKSON AVE	POTSDAM	NY	13676	SAINT LAWRENCE	USA	Biomedical Research and Research Training	000	1	7/12/2022	NEW	$363,102
														Subtotal = $363,102

Grand Total All Awards = $2,107,167

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Development and Application of Organelle Chemotype Fingerprinting for the Functional Investigation of Organellar Chloride

Award Number: R35GM147112

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: 08/01/2022

PERIOD OF PERFORMANCE END DATE: 11/03/2025

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