# Multi-level Integrative Proteomics to Alzheimer's Disease Pathways

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2020 · $440,000

## Abstract

The long-term goal of this project is to develop and apply the latest proteomics approaches to understand
molecular dysfunction underlying the pathogenesis of Alzheimer's disease (AD). Dissection of molecular
composition (e.g. DNAs, RNAs, and proteins) in clinical specimens is critical for understanding, detecting,
preventing and treating disease. The evolving DNA technology has been revolutionizing medical research and
patient care. National Institute on Aging has invested tens of millions of dollars to search for AD risk genes. In
contrast, proteomic research is being left behind, largely due to the limitations of technology. Our lab has been
developing proteomics approaches for ultra-sensitivity and high throughput for more than a decade. Recently,
we have implemented a highly sophisticated platform for profiling more than 10,000 proteins. To explore the
proteome alteration in human AD brains, we and collaborators initiated a study to analyze aggregated
proteome, revealing unique U1 snRNP pathology in AD and raising a novel concept of RNA splicing alterations
in the pathogenesis. Thus, we propose to further enhance the proteomics platform with milestones, and profile
AD mouse and human brain proteomes, as well as the interactome of AD disease proteins, for identifying novel
pathogenic mechanisms. Three specific aims are: (i) to establish a multiplex, quantitative platform for nearly
complete coverage of human proteome as well as comprehensive protein modification analyses, (ii) to identify
aberrant protein pathways in AD by profiling the whole proteome and protein modifications in human and
mouse models, and (iii) to determine AD disease pathways by the interactome of AD disease proteins in
human. Successful outcome of this project will enable truly global proteomic studies of clinical samples,
matching the coverage of genomics. The AD study may provide novel targets for pathogenesis and therapeutic
intervention.

## Key facts

- **NIH application ID:** 9949576
- **Project number:** 5R01AG053987-05
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** JUNMIN PENG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $440,000
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9949576

## Citation

> US National Institutes of Health, RePORTER application 9949576, Multi-level Integrative Proteomics to Alzheimer's Disease Pathways (5R01AG053987-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9949576. Licensed CC0.

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