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Methods for measuring matrisome molecule similarity during disease processes

Award Number: R35GM144090
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: 03/01/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Methods for measuring matrisome molecule similarity during disease processes - Project Summary/Abstract: The application responds to NIGMS PAR-19-367 “Maximizing Investigators' Research Award (R35 - Clinical Trial Optional)” My research group focused initially on analytical methods for glycosaminoglycans (GAGs). These linear, sulfated polysaccharides are attached to serine residues of proteoglycan molecules found on cellular surfaces, in intracellular granules and in extracellular matrices. Binding interactions between GAGs and proteins are central to aspects of animal physiology including cellular signaling, the cellular microenvironment, and host- host, and host-pathogen recognition. My group developed methods for liquid chromatography-mass spectrometry analysis and sequencing of GAGs, extraction of GAGs from wet tissue and tissue slides, and bioinformatics programs for interpretation of GAG MS and tandem MS data. We then pioneered methods to acquire glycomics (GAGs and N-glycans) and proteomics from biospecimen tissue slides. We applied these methods to study of neurological aging, cancer, neurodevelopmental, and neurodegenerative diseases. As funded through NIGMS R01GM133963 “Methods for determination of glycoprotein glycosylation similarities among disease states”, my group is developing analytical and bioinformatics methods for glycoproteomics of the extracellular matrix molecules (known as the matrisome) of brain. The primary focus has been on glycoproteomics MS acquisition methods and bioinformatics for rigorous statistical determination of molecular similarities for matrisome molecules and how these change during normal aging versus disease processes. I now propose to expand our brain glycoproteomics molecular similarity scope to include characterization of GAGs that modify specific matrisome molecules. Our goals will be to provide information on the pathophysiological changes to matrisome molecules that escape detection using traditional antibody-based detection methods. We will employ a new Omnitrap platform to characterize multiply glycosylated peptides and peptides modified with GAG chains. We will also exploit the capabilities of ion mobility for measuring molecular similarities from glycoproteomics data using a Waters Cyclic ion mobility-mass spectrometry instrument. We will demonstrate these approaches by comparing matrisome molecular similarity among brain regions and as a function of age.


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 = $371,250 )
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Biomedical Research and Research Training	001	4	3/21/2025	NON-COMPETING CONTINUATION	$371,250
2025	2024	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Biomedical Research and Research Training	000	3	11/8/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $371,250

Issue Date FY: 2024 ( Subtotal = $412,500 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Biomedical Research and Research Training	000	3	2/26/2024	NON-COMPETING CONTINUATION	$371,250
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Biomedical Research and Research Training	001	3	6/18/2024	NON-COMPETING CONTINUATION	$41,250
														Subtotal = $412,500

Issue Date FY: 2023 ( Subtotal = $412,500 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Biomedical Research and Research Training	000	2	2/10/2023	NON-COMPETING CONTINUATION	$412,500
														Subtotal = $412,500

Issue Date FY: 2022 ( Subtotal = $437,250 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Biomedical Research and Research Training	000	1	2/28/2022	NEW	$272,250
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Biomedical Research and Research Training	001	1	9/21/2022	SUPPLEMENT FOR EXPANSION	$165,000
														Subtotal = $437,250

Grand Total All Awards = $1,633,500

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Methods for measuring matrisome molecule similarity during disease processes

Award Number: R35GM144090

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: 03/01/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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