# Administrative Supplement for Imaging Equipment Purchase

> **NIH NIH R35** · NORTH CAROLINA AGRI & TECH ST UNIV · 2024 · $248,912

## Abstract

PROJECT SUMMARY/ ABSTRACT. This Equipment Supplement project seeks to acquire a high-resolution
fluorescent microscope to advance the goals of my R35 MIRA project. The MIRA supported research program
focuses on understanding the cellular and molecular mechanisms underlying the progression of tissue injury
mediated by meprin metalloproteases. Two goals in the project rely heavily on microscopic imaging technology
with complementary software for quantitation of the staining intensity as a measure of protein expression
levels. Meprins comprise of two subunits, α and β, which form two protein isoforms, meprin A (α-α or α-β) and
meprin B (β-β) with distinct and overlapping substrates. Meprins are most abundantly expressed in the brush-
border membranes of proximal kidney tubules and small intestines. Meprins are also expressed in leukocytes
(monocytes and macrophages), podocytes, skin, endothelial cells, and cancer cells. Meprins have been
implicated in the pathophysiology of inflammatory- and fibrosis-associated diseases that include kidney
disease, inflammatory bowel disease, lung fibrosis, neurodegenerative disease (e.g. Alzheimer’s disease), and
cancer. Single nucleotide polymorphisms (SNPs) in the meprin β gene were shown to associate with severity
of certain diseases such as diabetic kidney disease and cancer. My research group uses a combination of
molecular biology and proteomic approaches to identify meprin substrates and characterize the interactions
between meprin isoforms and their substrates. These are coupled with in vivo studies with meprin knockout
mouse models to determine how meprin activity impacts the progression of disease. Known meprin substrates
include extracellular matrix (ECM) proteins, modulators of inflammation (e.g. proinflammatory cytokines [IL-1β,
IL-6, IL-18, MCP-1; and anti-inflammatory proteins Ac-SDKP), cell signaling proteins (e.g. protein kinase A and
protein kinase C), mediators of the hypoxia response (e.g. osteosarcoma-9), tight junction proteins (e.g.
claudin 5, occludin, E-cadherin, and Z0-1) cytoskeletal proteins (e.g. villin and actin) and proteins that
contribute to plaques in AD (e.g. amyloid precursor protein and triggering receptor expressed on myeloid cells
2). The diversity of meprins substrates suggests that complex mechanisms are involved under different
conditions and in different organs. It’s important to gain understanding of these mechanisms to facilitate
development of diagnostic and therapeutic tools. For the MIRA proposal, we are conducting studies in three
areas; (i) to determine how SNPS in the meprin β gene impact its interactions with substrates and
physiological sheddases, (ii) determine how meprin interactions with substrates modulate signaling pathways
and impact responses in hypoxia, inflammation, and ECM metabolism, and (iii) to evaluate the use of meprin
and meprin cleavage products as biomarkers for development of diagnostic tools for early detection of disease.
The proposed researc...

## Key facts

- **NIH application ID:** 11099275
- **Project number:** 3R35GM141537-04S1
- **Recipient organization:** NORTH CAROLINA AGRI & TECH ST UNIV
- **Principal Investigator:** Elimelda Moige Ongeri
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $248,912
- **Award type:** 3
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11099275

## Citation

> US National Institutes of Health, RePORTER application 11099275, Administrative Supplement for Imaging Equipment Purchase (3R35GM141537-04S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/11099275. Licensed CC0.

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