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Determining the signatures of pan-ubiquitylation in the immune proteome as highly sensitive and effective markers for neurodegenerative disease

Award Number: R43AG062061
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2019
PERIOD OF PERFORMANCE END DATE: 05/31/2021

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Determining the signatures of pan-ubiquitylation in the immune proteome as highly sensitive and effective markers for neurodegenerative disease - SUMMARY: Alzheimer's disease (AD) is the most devastating age-related disease due to its damage to cognitive and motor capacity, heavily care-dependent nature, and lack of early diagnostics and effective therapeutics. The first step toward its cure is to discover early-stage molecular markers based on its fundamental pathogenesis: accumulation of protein aggregates in plaques and chronic proinflammation. The main biochemical regulatory mechanism governing these two cellular events is post-translational modification of proteins by ubiquitin (Ub) and ubiquitin-like proteins (Ubls). Circulating immune cells in blood and cerebrospinal fluid (CSF) provide a means of liquid biopsy to monitor protein degeneration in the brain. We hypothesize that the signature of the Ub and Ubl immune proteome serves as a marker for AD. However, the precise information encoded in these Ub/Ubl modification sites is poorly understood. This is mainly due to a lack of reagents to selectively isolate Ub- or Ubl-conjugated peptides from protease-treated cell lysates. We will develop methods to allow the specifically isolation and identification of Ub or Ubl conjugation sites at the proteome level. This will be accomplished by developing a novel affinity matrix to specifically enrich the ubiquitin remnants generated from protease digestion, resulting in optimal quantification by mass spectrometry analysis. Using this technology, we will identify the bona fide pan-ubiquitylation patterns of the immune proteome as a pathological fingerprint for neurodegeneration. The success of this project will provide the first comprehensive pan-ubiquitin immune proteome to monitor and diagnose AD.


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: 2022 ( Subtotal = $0 )
2022	2019	LIFESENSORS INC	271 GREAT VALLEY PKWY	MALVERN	PA	19355	CHESTER	USA	Aging Research	000	1	11/15/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $224,828 )
2019	2019	LIFESENSORS, INC.	271 GREAT VALLEY PKWY	MALVERN	PA	19355	CHESTER	USA	Aging Research	000	1	5/29/2019	NEW	$224,828
														Subtotal = $224,828

Grand Total All Awards = $224,828

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Determining the signatures of pan-ubiquitylation in the immune proteome as highly sensitive and effective markers for neurodegenerative disease

Award Number: R43AG062061

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2019

PERIOD OF PERFORMANCE END DATE: 05/31/2021

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