# From single molecule to microfluidic 3D tissue platforms: novel multiscale tools to investigate hyper-stimulated immune cells in the circulation

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2024 · $608,419

## Abstract

PROJECT SUMMARY
The exact mechanism underlying the onset of Multiple Sclerosis (MS), a disease that affects over 2 million people
worldwide and ~ 400,000 in the United States, is unknown although most experts in the field agree that MS
involves an abnormal immune-mediated response against the body’s central nervous system (CNS).
Specifically, in the CNS, components of the immune system attack myelin, the protein-based substance that
surrounds nerve fiber. This attack on myelin results in multiple scar lesions (hence, Multiple Sclerosis) that lead
to disease symptoms. Mounting evidence suggests that a breakdown in the blood brain barrier (BBB) enables
the permeability of toxins and other foreign pathogens into the CNS that attack the myelin. Here, an investigative
team with basic and clinical science experience proposes that hypermetabolic red blood cells (RBCs) in the MS
circulation are contributing to increased glucose utilization in the brain and subsequent BBB breakdown.
Specifically, during our previous project period, the investigative team discovered and recently published several
interesting findings involving the MS RBC. First, the MS RBC has a significantly increased amount of the GLUT1
glucose transporter in its membrane. The GLUT1 transporter is the dominant glucose transporter in the RBC
(and most circulatory cells) and is not affected by insulin. Secondly, we reported that C-peptide, the 31-amino
acid peptide that is co-secreted in equal molecule amounts with insulin from the pancreatic -cells, binds to the
MS RBC at a level nearly 50% higher than control RBCs and RBCs obtained from people with other neurological
diseases (ONDs, as rigorous controls). Finally, we reported an increase in ATP release from the MS RBC upon
stimulation, indicating increased glycolysis. Collectively, our data and other recent data in the literature from
other groups, suggest MS RBCs are hypermetabolic. The link to the compromised BBB occurs when considering
recent impactful work in the literature that supports decades-old reports of hypermetabolic RBCs in people with
MS. The increased metabolism results in a significant increase in lactic acid (lactate) production in the MS
circulation, which may compromise BBB integrity through localized changes in pH. During the renewal project
period, the investigative team plans to deepen our understanding of MS by further developing novel tools to
study the MS RBC at the single cell level, as well as in humans, with novel in vivo imaging strategies. We will
also better power our previous studies by increasing the number of MS patients at the different stages of MS.
These aims will inform an in vivo PET/MRI clinical study in years 4-5 designed to determine glucose utilization
before and after normal dosing of interferon-beta (IFN-, a common MS disease modifying therapy), thereby
providing impactful information on the mechanism of MS disease onset.

## Key facts

- **NIH application ID:** 10881306
- **Project number:** 2R01NS105888-06A1
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Lane A. Baker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $608,419
- **Award type:** 2
- **Project period:** 2018-04-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10881306

## Citation

> US National Institutes of Health, RePORTER application 10881306, From single molecule to microfluidic 3D tissue platforms: novel multiscale tools to investigate hyper-stimulated immune cells in the circulation (2R01NS105888-06A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10881306. Licensed CC0.

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