NIH Reporter #1U19AG097398-01

Core 2: Multi-omics Core

Award to Emory University for the Core 2: Multi-omics Core project under the National Institute on Aging. The project aims to generate comprehensive multi-omics data to identify Alzheimer’s disease subtypes and therapeutic targets using advanced molecular and spatial profiling techniques. The award supports research from 2026 to 2031 with a funding amount of $2,731,122.

Description

The Multi-Omics Core (MOC) is designed to generate comprehensive molecular data supporting the two project and overarching goals of the TARGET-AD consortium. By integrating genomics, transcriptomics, proteomics, metabolomics/lipidomics, and single-nucleus/cell RNA sequencing (penta-omics), the core will provide harmonized datasets from human brain tissue, matched blood, and iPSC-derived cultures to identify and validate Alzheimer’s disease (AD) subtypes and their candidate therapeutic targets. The MOC is structured around three primary aims: Aim 1: Generate penta-omic data from well-characterized human cohorts (ROSMAP and MCSA), enabling the identification of molecular subtypes across matched brain and antemortem blood samples. Aim 2: Extend this approach to iPSC-derived models, conducting omics profiling following chemical and genetic target perturbations using AD-informer set compounds, antisense oligonucleotides (ASOs), and CRISPR genome editing. Aim 3: Employ high-dimensional spatial profiling (Xenium and 4i imaging) to map subtype-specific molecular targets within brain tissue, providing insights into disease mechanisms and cell-type expression. To achieve these aims, the MOC utilizes cutting-edge mass spectrometry for proteomics and metabolomics, advanced sequencing and imaging platforms for high-throughput, high-resolution multi-omics data generation, and the innovative Alamar NuLISA platform to measure established AD biomarkers. Harmonized protocols will be implemented to minimize batch effects and optimize data reproducibility. The MOC collaborates closely with other cores to ensure seamless data integration and dissemination, facilitating the discovery of candidate subtype-specific therapeutic targets and advancing AD precision medicine initiatives.

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