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Chemical Glycoproteomics

Award Number: R01CA200423
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2002
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Chemical Glycoproteomics - PROJECT SUMMARY Mucins are densely O-glycosylated proteins with extended regions of clustered Ser/Thr-linked O-glycans, a structural feature that imparts a rigid and extended conformation. Their range of biological functions include physical stiffening of the glycocalyx to modulate cell survival in low adhesion settings, and biochemical interactions with glycan-binding receptors on other cells. Altered mucin expression and glycosylation patterns have been strongly linked to cancer progression. Crude measurements of these changes are currently used for cancer diagnosis but are imperfect due to their lack of molecular-level detail. A detailed map of mucin O-glycan structures and sites has been impossible to obtain, as mucins are recalcitrant to conventional mass spectrometry-based glycoproteomics methods. As a consequence, the cellular pathways underlying aberrant mucin structures are not well defined. We are pursuing these questions with the long-term goal of identifying more accurate cancer biomarkers and new therapeutic targets. During the previous funding period, we developed new mass spectrometry-based glycoproteomics methods and used them in fundamental studies of the enzymes that initiate mucin-type O-glycosylation, the polypeptide GalNAc transferases. Examples of our accomplishments include (i) development of the IsoTaG method for intact glycoproteomics via isotopic recoding and mass-independent glycopeptide discovery; (ii) identification of an optimal tandem mass spectrometry method for O-glycosite discovery; and (iii) development of a bump/hole strategy to identify biological substrates of polypeptide GalNAc transferases that initiate mucin-type O- glycosylation. In preliminary work for this application, we repurposed mucin-specific proteases (“mucinases”) from gut-resident microbes as tools for mapping O-glycosites on mucin domains. In the next funding period, we plan to develop a comprehensive “mucinomics” platform. We will use engineered mucinases as glycoform-sensitive probes of mucin expression on cells and tissues. We will also develop a mucinase-based enrichment strategy for mass spectrometry-based discovery of new mucin domain molecules as well as O-glycosite mapping. Integrated into this workflow will be newly developed ionization methods and search algorithms for O-glycosite identification. Finally, we will use the mucinomics platform to define pathways by which prevalent oncogenes drive altered mucin expression and glycosylation in cancer.


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 = $337,180 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	22	5/16/2025	NON-COMPETING CONTINUATION	$337,180
														Subtotal = $337,180

Issue Date FY: 2024 ( Subtotal = $344,925 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	21	5/31/2024	NON-COMPETING CONTINUATION	$318,518
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	001	21	7/19/2024	SUPPLEMENT FOR EXPANSION	$26,407
														Subtotal = $344,925

Issue Date FY: 2023 ( Subtotal = $333,646 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	001	20	9/15/2023	NON-COMPETING CONTINUATION	$6,674
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	20	6/7/2023	NON-COMPETING CONTINUATION	$326,972
														Subtotal = $333,646

Issue Date FY: 2022 ( Subtotal = $326,899 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	19	6/7/2022	NON-COMPETING CONTINUATION	$326,899
														Subtotal = $326,899

Issue Date FY: 2021 ( Subtotal = $333,035 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	18	3/25/2021	COMPETING CONTINUATION	$333,035
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	002	18	9/3/2021	COMPETING CONTINUATION	$108
2021	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	001	17	9/3/2021	NON-COMPETING CONTINUATION	-$108
														Subtotal = $333,035

Issue Date FY: 2019 ( Subtotal = $335,039 )
2019	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	17	5/9/2019	NON-COMPETING CONTINUATION	$335,039
														Subtotal = $335,039

Issue Date FY: 2018 ( Subtotal = $347,383 )
2018	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	16	5/11/2018	NON-COMPETING CONTINUATION	$347,383
														Subtotal = $347,383

Issue Date FY: 2017 ( Subtotal = $349,310 )
2017	2017	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	15	5/23/2017	NON-COMPETING CONTINUATION	$349,310
														Subtotal = $349,310

Issue Date FY: 2016 ( Subtotal = $351,178 )
2016	2016	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	14	6/23/2016	NON-COMPETING CONTINUATION	$351,178
														Subtotal = $351,178

Issue Date FY: 2015 ( Subtotal = $365,056 )
2015	2015	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	13	6/23/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$365,056
														Subtotal = $365,056

Grand Total All Awards = $3,423,651

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Chemical Glycoproteomics

Award Number: R01CA200423

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2002

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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