# Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targets

> **NIH NIH U01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $1,215,000

## Abstract

In the first period of the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD), we
completed an arc of novel target validation that began with molecular network construction and confirmation,
progressed to identifying driver genes within the network, and ended with target gene validation, through both
in vitro perturbation and proteomic measurement in the target organ. Here, we characterize those validated
genes in greater detail and deploy a third-generation network map that incorporates data from single cells
extracted from 500 brains to produce a cell-type specific version of our networks. Further, in the discovery
phase, we will use an assessment of protein post-translational modifications to identify targets that are typically
masked in the tissue-level brain RNA and generic protein levels that have been available to date. The new
network will also integrate the latest AMP-AD data, spanning genomic, transcriptomic, epigenomic, proteomic,
and metabolomic data sets from the various member groups. The resulting new targets, along with those
validated in the first funding cycle, will undergo further dissection to understand which protein isoform or
modification is most relevant to disease. We go on to perform perturbation experiments for each of the
prioritized genes in an enriched in vitro multicellular culture context and to identify critical protein domains
within selected candidates. Finally, we expand our Research Resource Sharing Hub that facilitates the
distribution of samples and data from our project.

## Key facts

- **NIH application ID:** 10071269
- **Project number:** 3U01AG061356-02S2
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** DAVID ALAN BENNETT
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,215,000
- **Award type:** 3
- **Project period:** 2018-09-30 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071269

## Citation

> US National Institutes of Health, RePORTER application 10071269, Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targets (3U01AG061356-02S2). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10071269. Licensed CC0.

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