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

> **NIH NIH U01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $416,605

## Abstract

ABSTRACT for parent currently funded U01
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:** 10375865
- **Project number:** 3U01AG061356-03S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** DAVID ALAN BENNETT
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $416,605
- **Award type:** 3
- **Project period:** 2018-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375865

## Citation

> US National Institutes of Health, RePORTER application 10375865, Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targets (3U01AG061356-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10375865. Licensed CC0.

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