# Research Supplements to Promote Diversity in Health-Related Research Mechanisms of APP ectodomain function

> **NIH NIH R35** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2024 · $17,901

## Abstract

Project Summary
The objective of the parent grant is to elucidate the normal physiological functions of the extracellular domain of
the Amyloid Precursor Protein (APP) in multiple cell types. Despite the known effects of the APP ectodomain on
cellular and cognitive functions and the potential applications to disease, the precise molecular mechanisms
mediating the function of the secreted APP ectodomain and the various forms of soluble APP generated by
ectodomain shedding are not well understood. Our approaches are designed to address the mechanistic gaps
in knowledge by leveraging our recent discovery that sAPP functions as a ligand for the GABA type B Receptor
(GABABR) and our recent identification of Phosphoglycerate Mutase Family Member 5 (PGAM5), a mitochondrial
serine/threonine protein phosphatase, as a novel candidate interactor of the APP ectodomain. One line of
research is aimed at elucidating the cellular responses of multiple cell types to sAPP and GABABR modulation,
identify signaling pathways downstream of the sAPP and GABABR interaction, and determine mechanisms
involved in the positive regulation of GABABR signaling by sAPP. The proposed research of the candidate in this
supplement is related to that line of research but is unique from the proposed studies in that he will examine the
effects and mechanisms involved in APP and GABABR signaling in developmental processes in neuronal cells,
which is an area of research that strongly aligns with the long-term research and career interests of the candidate.
The candidate will also expand on their background and interest in biophysics to establish intravital imaging
techniques and address the in vivo relevance of the APP- GABABR interaction.

## Key facts

- **NIH application ID:** 11031210
- **Project number:** 3R35GM142726-04S1
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** HEATHER C. RICE
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $17,901
- **Award type:** 3
- **Project period:** 2021-09-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11031210

## Citation

> US National Institutes of Health, RePORTER application 11031210, Research Supplements to Promote Diversity in Health-Related Research Mechanisms of APP ectodomain function (3R35GM142726-04S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11031210. Licensed CC0.

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