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Molecular probes for targeting facilitative fructose transporters (GLUTs) in biochemical and biomedical applications

Award Number: R15CA242401
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/03/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Molecular probes for targeting facilitative fructose transporters (GLUTs) in biochemical and biomedical applications - PROJECT SUMMARY The primary goal is to advance the development of GLUT-targeting molecular probes to facilitate the characterization of cells and discrimination between cancer and normal cells. High sugar uptake has long been identified as a hallmark of cancer. Recently, the specific dependence of cancers on fructose for development and progression outlined fructose uptake as a potential diagnostic and therapeutic target. Respectively, changes in the activity of facilitative fructose transporters (GLUTs) and alterations in the overall GLUT profile between normal and metabolically compromised cells have set the foundation for developing GLUT-based approaches to target cancer cells. However, specific targeting of disease-relevant fructose GLUTs remains a challenge, limiting the use of GLUTs in diagnostic and therapeutic applications. The proposed research program demonstrates the targeting of selected fructose GLUTs (GLUT2, GLUT12, and GLUT5) for identifying fructose-dependent cells in imaging applications. The proposal addresses several challenges in developing GLUT-specific molecular probes, GLUT-targeting cell imaging, and GLUT activity screening approaches. The primary innovative component enables discrimination between nonspecific fructose GLUTs allowing for designing specific molecular probes for several cancer-relevant fructose transporters. The developments proposed in this research include approaches for GLUT-based cell profiling, GLUT-based characterization of cancer cells, and GLUT- based in vivo imaging. The direct outcomes of this research include the validation of a novel multi-color multi- GLUT screening approach for measuring GLUT5:GLUT2 activity ratios through fluorescence and novel turn-on fluorescent molecular probes for real-time monitoring and high-throughput fluorescence screening of GLUT activity. The project will yield a new GLUT-based characterization of different breast cancer cell lines and identify the fructose-dependent cell lines potentially targeted for in vivo imaging by GLUT-specific probes. The project also advances the specific targeting of fructose GLUTs in vivo by developing GLUT-specific imaging probes for PET applications. The research project is designed to be carried out primarily by undergraduate students under the supervision of the PI and a graduate researcher. The program provides a comprehensive multidisciplinary educational platform for undergraduate and graduate researchers and offers a hands-on research experience at the interface of chemistry and biology. By engineering probes that can specifically target other fructose or glucose transporters, we will advance to fingerprinting GLUTs to characterize and distinguish cells. GLUT-specific probes will enable fundamental studies to foster an understanding of the impact of each GLUT and different dietary sugars at the molecular level on health and disease.


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: 2024 ( Subtotal = $455,433 )
2024	2024	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cancer Detection and Diagnosis Research	000	2	12/6/2023	COMPETING CONTINUATION	$455,433
2024	2024	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cancer Detection and Diagnosis Research	002	2	4/18/2024	COMPETING CONTINUATION	$1,830
2024	2019	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cancer Detection and Diagnosis Research	001	1	4/18/2024	NEW	-$1,830
														Subtotal = $455,433

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2019	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cancer Detection and Diagnosis Research	000	1	1/13/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $446,849 )
2019	2019	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cancer Detection and Diagnosis Research	000	1	7/3/2019	NEW	$446,849
														Subtotal = $446,849

Grand Total All Awards = $902,282

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Molecular probes for targeting facilitative fructose transporters (GLUTs) in biochemical and biomedical applications

Award Number: R15CA242401

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/03/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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