# Functional validation of the SMOC1 matrisomal protein network in Alzheimers disease

> **NIH NIH K01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $102,918

## Abstract

Project Summary/Abstract
This proposal describes a five-year mentored laboratory training experience designed to lead to an independent
academic research career dissecting the underlying biology of Alzheimer’s disease (AD). The applicant’s career
goal is to become a prominent scientist in the AD research filed by leading an independently funded research
group. The career development plan includes training designed to broaden the applicant’s scientific skillset by:
(1) employing translational approaches to identify and characterize key proteins of an AD-associated network to
determine how they contribute to AD pathogenesis, (2) utilizing systems biology approaches to dissect network
behavior when key interconnected proteins are perturbed and (3) using cross-species approaches to identify
additional proteins linked to specific AD pathological triggers as therapeutic targets in the fight against AD. This
plan incorporates additional training in leadership, mentorship, grant-writing, and ethics. During the period of
mentored research training, the applicant will engage in skills acquisition, didactic training, seminars,
international conferences, and meetings with his mentor and mentorship committee, followed by a transition to
independence. The proposed research aims to improve our understanding of the biology underlying AD
progression through investigation of an AD-associated protein network. We have identified the human M42
network that is strongly correlated with pathology and declining cognition in AD. Based on network analyses,
SPARC Related Modular Calcium Binding-1 (SMOC1) was identified as a potential network driver that best
represents the behavior of the entire network. The overall project goal is to validate and elucidate the role of
M42 by dissecting SMOC1 function in the Drosophila model. My cross-species approach will powerfully enhance
our understanding of SMOC1 in the adult brain, which is predicted to modulate both TGFβ and wnt/β-catenin
signaling pathways, and identify additional M42 proteins important in AD pathology, thus informing a therapeutic
rationale for further studies in mammalian preclinical AD models. This five year project will take place primarily
at Baylor College of Medicine, an institution with nationally recognized research programs in genetics,
neuroscience and AD. The Department of Neurology has an outstanding track record of training early stage
investigators to become successful translational researchers. The research environment provides the best
intellectual environment, cutting edge technologies and state-of-the art facilities. The proposal provides a broad
research experience in systems biology analysis of proteomic data, cross-species validation of a translationally
relevant protein network, along with functional characterization of its proposed driver protein SMOC1, a novel
biomarker and potential therapeutic target in AD. Completion of this proposal and its associated training plan
will prepare this appl...

## Key facts

- **NIH application ID:** 10754956
- **Project number:** 5K01AG080078-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** David Edward Li-Kroeger
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $102,918
- **Award type:** 5
- **Project period:** 2023-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10754956

## Citation

> US National Institutes of Health, RePORTER application 10754956, Functional validation of the SMOC1 matrisomal protein network in Alzheimers disease (5K01AG080078-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10754956. Licensed CC0.

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