# Construction, Analysis, and Utilization of Co-Phosphorylation Networks to Characterize Cellular Signaling

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $388,529

## Abstract

Proteomic and phospho-proteomic data derived from mass spectrometry experiments offer unique opportunities
to interrogate cellular signaling pathways and networks in an unbiased and comprehensive manner. The role of
phosphorylation linked signaling processes in the development of Alzheimer's Disease (AD) is well-established,
yet little is known about gender, age/disease stage,tissue, and etiology based variations in this signaling. This
supplement will provide novel data that pertains to this cellular signaling, and the parent R01 provides novel
computational tools for systems-level analysis of proteomic and phosphoproteomic data essential to
characterizing the signaling landscape of Alzheimer's Disease.
 In the parent award, R01-LM-012980 (funded under PAR-18-896), we are developing enabling systems
and network-based analyses of phosphoproteomic data in the context of a broad range of biomedical problems.
Our project is advancing the field through development of algorithms for predicting kinase-substrate associations,
inference of kinase activity, and identification of context-specific changes in cellular signaling. An opportunity to
expand the focus of this award around Alzheimer's disease models exists due to an emerging collaboration with
Dr. Mark Chance (proteomics expert, co-investigator for parent award) and Dr. Xin Qi (neurodegenerative
disease expert, consultant for parent award). These co-investigators recently received supplemental funding
from NIGMS/NIA (3 R01 GM117208-03S1) to collect pivotal proteomics and phosphoproteomics data on brain
tissue from the 5XFAD AD mouse model at various stages of disease development. The temporal progression
of the plaque-centered disease in the 5XFAD mouse model highlights the initial development of
neuroinflammation “proteomic phenotypes” followed by neurodegeneration-linked molecular phenotypes,
including specific upregulation of many Alzheimer's related proteins like synucleins and tau from data examined
in the hippocampus.
 In this supplement under (NOT-AG-18-008), we will leverage our network-based algorithms to accelerate
AD research by further characterizing the specific signaling changes that underlie neuronal degeneration in a
tauopathy mouse model (PS19) as a function of gender, stage of development, and tissue type to provide
complementary basic science systems level understanding of disease progression in AD mouse models. Using
these mouse models , we will identify signaling networks composed of specific kinases, substrates, and
phosphorylation sites that exhibit dysregulation in male and female mice representing different etiologies of
Alzheimer's Disease (Supplement Aim 1) and potential biomarkers that can aid in the diagnosis and prognosis
of Alzheimer's Disease at different stages (Supplement Aim 2).

## Key facts

- **NIH application ID:** 10289148
- **Project number:** 3R01LM012980-03S1
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Mehmet Koyuturk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $388,529
- **Award type:** 3
- **Project period:** 2019-07-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10289148

## Citation

> US National Institutes of Health, RePORTER application 10289148, Construction, Analysis, and Utilization of Co-Phosphorylation Networks to Characterize Cellular Signaling (3R01LM012980-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10289148. Licensed CC0.

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