Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Chemical Approaches to Understand O-GlcNAc Glycosylation and Its Roles in Neurodegeneration

Award Number: R01AG060540
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2002
PERIOD OF PERFORMANCE END DATE: 04/30/2029

Group Awards By:

View Award Description

Chemical Approaches to Understand O-GlcNAc Glycosylation and Its Roles in Neurodegeneration - Project Summary/Abstract Carbohydrates (also known as glycans) comprise one of the largest, most diverse collections of biologically active molecules. However, relative to other biomolecules such as nucleic acids and proteins, carbohydrates remain poorly understood due to challenges in their detection, synthesis, and analysis. The broad objective of this program is to develop chemical approaches to advance a fundamental understanding of the roles of carbohydrates in biology and disease. In the last granting period, we developed a novel Networking of Interactors and SubstratEs (NISE) method to study the biological functions of O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation. O-GlcNAc is an abundant, essential post-translational modification that is emerging as a key regulator of many physiological functions, ranging from epigenetic and transcriptional gene regulation to insulin signaling, cancer cell metabolism, and neurodegeneration. Our NISE approach combines new chemoproteomic tools, genetic engineering, mass spectrometry analysis, and bioinformatics methods to quantitatively profile O- GlcNAc sites and O-GlcNAc transferase (OGT) interactors across the proteome and to determine key interconnections between the interactors and substrates. The resulting networks have revealed novel, unexpected functions for O-GlcNAc and highlighted potential mechanisms to explain the unique specificity of OGT. In the coming granting period, we will expand on this approach and investigate the roles of O- GlcNAcylation in neurons and in the context of neurodegenerative diseases as we continue to tackle the next critical barriers in the field. In Aim 1, we will focus on understanding how O-GlcNAcylation within intrinsically disordered, low-complexity domains of proteins affects their functions and alters biomolecular condensate (BMC) formation, composition, and dynamics. These studies should provide new paradigms and methods for understanding the fundamental mechanisms by which O-GlcNAc regulates proteins and its role in aberrant BMC activity linked to Alzheimer’s disease and related dementias (AD/ADRDs). In Aim 2, we will test specific hypotheses revealed by our NISE networks regarding the regulation of OGT activity at neuronal synapses and specifically toward proteins implicated in AD/ADRDs. In Aim 3, we will apply our NISE method to examine directly how O-GlcNAcylation of specific proteins and pathways becomes dysregulated during AD pathogenesis and with disease-specific mutations by using patient-derived induced pluripotent stem cells (iPSCs) and human AD brain samples. Together, the proposed studies will provide a powerful approach to identify and understand physiologically important and/or disease-causing O-GlcNAcylation events. In turn, this information is expected to provide new potential therapeutic targets and/or strategies to combat progressive neurodegeneration and AD/ADRDs.


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 = $793,874 )
2026	2026	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Aging Research	000	16	5/28/2026	NON-COMPETING CONTINUATION	$793,874
														Subtotal = $793,874

Issue Date FY: 2025 ( Subtotal = $781,082 )
2025	2025	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Aging Research	001	15	6/13/2025	NON-COMPETING CONTINUATION	$63,762
2025	2025	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Aging Research	000	15	4/3/2025	NON-COMPETING CONTINUATION	$717,320
														Subtotal = $781,082

Issue Date FY: 2024 ( Subtotal = $821,056 )
2024	2024	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Aging Research	000	14	7/15/2024	COMPETING CONTINUATION	$821,056
														Subtotal = $821,056

Grand Total All Awards = $2,396,012

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Chemical Approaches to Understand O-GlcNAc Glycosylation and Its Roles in Neurodegeneration

Award Number: R01AG060540

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2002

PERIOD OF PERFORMANCE END DATE: 04/30/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer