Development of human microphysiological systems for testing of ad/adrd interventional strategies across genetically diverse populations
Active Cooperative Agreement Awarded Last action
- Award ID
- U54AG090669
- Recipient
-
Brigham & Womens Hospital Inc. UEI QN6MS4VN7BD1 Part of Partners Healthcare System Incorporated
- Awarding agency
-
National Institute on Aging
National Institutes of Health, Department of Health and Human Services
- Obligated
- $7,917,428
Award facts
- Assistance listing
- 93.310 Trans-NIH Research Support
- Completion date 26% complete
- Funding agency
- Office of the Director National Institutes of Health, Department of Health and Human Services
- Place of performance
- Boston, MA 02115, USA
Award details come from USAspending.gov.
Description
- Abstract
- Overall component alzheimer's disease manifests along a spectrum of levels of neuropathology, age of onsets and rates of cognitive decline. Genetic studies support a heterogeneous etiology, with around 70 associated loci, implicating several biological processes that mediate risk for ad. Studies are just beginning to emerge that attempt to provide frameworks for subtyping ad based upon biomarker data, genetic data and/or -omics profiles from the postmortem brain. Despite this, the majority of experimental systems for testing new therapeutics are not designed to capture the genetically complex drivers of ad. In turn, past clinical trials may have suffered from an inability to predict individual responsiveness based upon the drivers of disease in ad subtypes. A one-size-fits- all approach to clinical trials and clinical care is unlikely to be successful across all cases (i.e. anti-amyloid immunotherapy may work well in a subset of cases but not in others). Successful establishment of the proposed precision-ad center, which will establish a toolkit of 2D and 3D microphysiological systems (MPS) that capture human genetic diversity underlying risk and resilience to ad and report on the function of biological domains relevant to ad, is an important first step in identifying convergent and divergent mechanisms of ad and testing person-specific responsiveness to therapeutic interventions. Here, we will leverage a set of ipsc lines that we recently developed from over 100 participants in the religious order study (ROS) and memory and aging project (map) that span ethnically diverse populations and include deeply phenotyped and genome sequenced individuals. Our ability to analyze matched brain and plasma from the same individuals provides a valuable opportunity for cross-platform validation of key molecular findings. Under this award, we have four overarching goals: 1) to generate an atlas of molecular signatures of 2D and 3D MPS experimental systems across 100 ethnically diverse genetic backgrounds that are matched with multi-omic data from brain tissue and plasma from the same individuals; 2) to develop preclinical efficacy assays for testing of six interventional strategies for ad that target different biological domains and to identify biomarkers of responsiveness to each intervention; 3) to establish rigorous, automated pipelines for scaling preclinical assays of efficacy to enable testing of interventional strategies across diverse genetic backgrounds, and 4) to establish robust pipelines for open-access sharing and distribution of MPS models, methods, and data to ensure facile distribution to scientists from the academic and biopharma communities. To accomplish these goals, we have assembled a multidisciplinary team with deep experience in alzheimer's biology, stem cell modeling, drug discovery, screening, lipidomics, proteomics, computational biology, and open resource sharing platforms. Together, we aim to develop 2D and 3D models as scalable platforms for the use as precision medicine research tools to investigate the complex biology of ad and to accelerate drug discovery and preclinical drug development.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $250,000 | |
| Amendment | $0 | |
| Amendment | $3,708,714 | |
| Original award | $3,708,714 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| Sloan-Kettering Institute For Cancer Research | $48,604 | |
| Jackson Laboratory | $672,787 | |
| Jackson Laboratory | $909,112 | |
| Rush University Medical Center | $89,549 | |
| New York Stem Cell Foundation Inc. | $508,040 | |
| New York Stem Cell Foundation Inc. | $391,188 | |
| Sage Bionetworks | $144,736 | |
| The Leland Stanford Junior University | $84,098 | |
| Icahn School Of Medicine At Mount Sinai | $1,277,278 | |
| Emory University | $64,610 | |
| Emory University | $503,738 | |
| Jackson Laboratory | $300,937 |
Show all 12
Quick answers
Who received award U54AG090669?
U54AG090669 was awarded to Brigham & Womens Hospital Inc. by National Institute on Aging (National Institutes of Health) on July 1, 2025.
How much is award U54AG090669 worth?
$7,917,428 has been obligated on U54AG090669.
Which agency awarded U54AG090669?
National Institute on Aging (National Institutes of Health) awarded U54AG090669, with funding from Office of the Director (National Institutes of Health).
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