Thursday, July 3, 2025 7/3/2025

AI-Powered Quantitative Systems Pharmacology for AD Drug Repurposing

Award Number: R01AG057555
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2017
PERIOD OF PERFORMANCE END DATE: 02/29/2028

Group Awards By:

View Award Description

AI-Powered Quantitative Systems Pharmacology for AD Drug Repurposing - Abstract Alzheimer's disease (AD) poses a triple threat to public health, as its prevalence is on the rise, its costs are immense, and there is no effective therapy. However, drug development attempts for the treatment of AD have met with minimal success. The failure is largely attributable to a reductionist concept of one drug, one gene, one disease. As AD is a multigenic heterogeneous illness, a new therapeutic strategy is urgently required to concurrently target the numerous pathogenic processes involved for the genesis and progression of AD in each individual patient. Many translational bioinformatics strategies for AD drug repurposing have been developed in recent years. Existing target-based, phenotype-based, network-based, and patient-based drug repurposing strategies are unable to fully address the challenges of AD drug repurposing due to the lack of thoroughly validated drug targets, potent lead compounds, and high-throughput phenotype readouts that can characterize the molecular complexity of AD. Over the past decade, we have built an artificial intelligence- based quantitative systems pharmacology (AI-QSP) platform that attempts to predict and characterize genome-wide chemical-protein interactions and functional activities, as well as correlate molecular interactions with phenotypic responses. Our AI-QSP platform integrates diverse omics data synergistically and incorporates machine learning, biophysics, and systems biology methodologies. The AI-QSP platform has been effectively applied to drug repurposing including AD, polypharmacology, side effect prediction, and precision medicine. Established our proof-of-concept studies, we propose to develop and thoroughly evaluate a unique computational methodology that combines target-based and mechanism-driven phenotypic chemical screening for AD individualized drug repurposing. Using a novel domain adaptation strategy, we will expand our context- independent phenotypic compound screening methodologies to AD patient-specific, cell type-specific, transcriptome-based drug repurposing. In addition, we will analyze the ADME features of repurposed pharmaceuticals in the human brain utilizing cutting-edge physiologically based pharmacokinetics (PBPK) techniques. We will improve state-of-the-art drug-gene-disease network models for Alzheimer's disease drug repurposing by incorporating understudied dark proteins that are abundant in the target list suggested by AD omics studies and their inhibitory or activatory effects, and by applying graph mining techniques for drug-gene- disease link predictions. Using cell-based disease models and RNA-seq studies, we will combine complementary phenotype-based and target-based techniques to rank drug candidates and confirm their efficacy and toxicity on AD treatment. In conclusion, the successful completion of this project could provide the scientific community with a novel translational bioinformatics resource for identifying potential therapeutics for effective personalized AD treatments and advancing drug repurposing to a new phase of lead optimizations and clinical trials.


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 = $706,510 )
2025	2025	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	695 PARK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	001	8	6/18/2025	NON-COMPETING CONTINUATION	$57,675
2025	2025	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	695 PARK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	000	8	4/14/2025	NON-COMPETING CONTINUATION	$648,835
														Subtotal = $706,510

Issue Date FY: 2024 ( Subtotal = $721,920 )
2024	2024	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	695 PARK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	002	7	2/21/2024	NON-COMPETING CONTINUATION	$649,729
2024	2024	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	695 PARK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	003	7	6/25/2024	NON-COMPETING CONTINUATION	$72,191
2024	2023	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	695 PARK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	001	6	2/14/2024	COMPETING CONTINUATION	$178,212
2024	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	695 PARK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	000	5	2/14/2024	NON-COMPETING CONTINUATION	-$178,212
														Subtotal = $721,920

Issue Date FY: 2023 ( Subtotal = $693,857 )
2023	2023	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	695 PARK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	001	6	5/31/2023	COMPETING CONTINUATION	$693,857
2023	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	695 PARK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	000	5	5/19/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $693,857

Issue Date FY: 2022 ( Subtotal = $779,392 )
2022	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	695 PARK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	000	5	6/2/2022	NON-COMPETING CONTINUATION	$779,392
														Subtotal = $779,392

Issue Date FY: 2021 ( Subtotal = $779,392 )
2021	2021	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	695 PARK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	000	4	6/16/2021	NON-COMPETING CONTINUATION	$779,392
														Subtotal = $779,392

Issue Date FY: 2020 ( Subtotal = $779,392 )
2020	2020	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	695 PARK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	000	3	4/21/2020	NON-COMPETING CONTINUATION	$779,392
														Subtotal = $779,392

Issue Date FY: 2019 ( Subtotal = $780,032 )
2019	2019	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	695 PARK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	001	2	6/10/2019	NON-COMPETING CONTINUATION	$779,392
2019	2018	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	695 PARK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	000	1	4/2/2019	NEW	$640
														Subtotal = $780,032

Issue Date FY: 2018 ( Subtotal = $779,392 )
2018	2018	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	695 PARK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	000	1	9/18/2018	NEW	$779,392
														Subtotal = $779,392

Grand Total All Awards = $6,019,887

Top

All Categories

About

Search

Reports

Data Submission

Award Information

AI-Powered Quantitative Systems Pharmacology for AD Drug Repurposing

Award Number: R01AG057555

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2017

PERIOD OF PERFORMANCE END DATE: 02/29/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer