# BLRD Merit Review Research Career Scientist Award

> **NIH VA IK6** · LOUISVILLE VA MEDICAL MEDICAL CENTER · 2024 · —

## Abstract

My research work largely explores the underlying physiologic questions regarding tiny vesicles called exosomes.
These exosomes are released from many different types of cells or food-derived exosome-like nanoparticles and
I am investigating in VA patients the promising role of exosomes as therapeutic vehicles in delivering treatment
for a diverse but specific group of medical conditions, i.e., inflammation related diseases including widespread
brain inflammation related diseases, obesity, rheumatoid arthritis, nonalcoholic fatty liver disease (NASH), and
cancer. The accumulation of inflammatory cells that release proinflammatory cytokines and chemokines not only
promote brain disease progression such as Gulf War Syndrome but also rheumatoid arthritis, obesity and/or
cancer. These diseases pose special burdens on veterans who depend on the VA for healthcare.
Since receiving my initial Research Career Scientist award, my research group has published more than 60
manuscripts on this subject. Collectively, our findings support continued funding of my team to investigate the
following aims: (1). Develop a therapeutic strategy to target delivery of therapeutic agents to microglia for
treatment of brain inflammation related diseases such as Gulf War Syndrome. Microglia cells respond vigorously
to both chronic disease and acute insults affecting brain function. Targeted delivery of therapeutic agents to
microglia is needed but highly challenging. The results published from my group (Theranostics, 2022,1220-1246,
Cell Host Microbe, 2022, 944-960, and Small 2022, 2105385) provide emerging evidence for the development
of edible exosome-like nanoparticles as a safe delivery system for targeting different tissues including brain
microglial cells, either by systemic or oral administration. (2). Investigate the role of tumor exosomes in
immunosuppression through induction of myeloid-derived suppressor cells, inhibition of dendritic cell
differentiation, and inhibition of activation of NK cell immunotherapy. This approach is supported based on our
published results (Nature Communications. 2017 Feb 17;8:14448, Nature communications. 2015;6:6956). (3).
Exosomes are released from non-tumor cells and we will determine their role in: (a) exosome accumulation in
adipose tissue (Diabetes. 2009 Nov;58(11):2498-505, Hepatology, 2013 57(3):1250-61), we will investigate the
role of adipose tissue exosome-like vesicles in activation of macrophage-induced insulin resistance and induction
of liver NKT cell anergy; and (b) investigate exosomes released from rheumatoid synovial fibroblasts and inhibit
regulatory T cell development. Their role in contributing to damaging joint cartilage will be further investigated.
(4). Based on the results we published as listed below, we will further develop customized exosome-like
nanoparticles from edible plants as therapeutic vehicles to treat/prevent specific disease. (a) Ginger exosome-
like nanoparticles (GELNs) are preferentially taken...

## Key facts

- **NIH application ID:** 10897357
- **Project number:** 1IK6BX006563-01
- **Recipient organization:** LOUISVILLE VA MEDICAL MEDICAL CENTER
- **Principal Investigator:** HUANG-GE ZHANG
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-04-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10897357

## Citation

> US National Institutes of Health, RePORTER application 10897357, BLRD Merit Review Research Career Scientist Award (1IK6BX006563-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10897357. Licensed CC0.

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