# BLR&D Research Career Scientist Award application

> **NIH VA IK6** · LOUISVILLE VA MEDICAL MEDICAL CENTER · 2020 · —

## 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.,obesity/diabetes, Nonalcoholic
fatty liver disease (NASH), and cancer. There is a substantial population of veterans who are obese and/or
have cancer. Obesity and cancer pose special burdens on veterans who depend on VA care. Obesity
contributes to over 300,000 deaths per year and increases the risk of NASH, type 2 diabetes, and several
cancers including colon, prostate, and kidney. Since receiving my initial Research Career Scientist award, my
research group has published more than 50 manuscripts on this subject. Collectively, our findings support
continued funding of my team to investigate the following 3 aims: (1) Tumor exosomes play a role in: (a)
immunosuppression through induction of myeloid-derived suppressor cells, inhibition of dendritic cell
differentiation, and inhibition of activation of NK cell immunotherapy; (b) by sorting suppressor miRNAs from
tumor cells into exosomes based on the oncogenic major vault protein (MVP), tumors grow faster (Nature
Communications. 2017 Feb 17;8:14448, Nature communications. 2015;6:6956); and (c) more recently, we
discovered a novel nanoparticle (Oncotarget. 2016 May 12). Unlike other EVs, this extracellular nanovesicle
(named HG-NV, HG-NV stands for HomoGenous nanovesicle as well as for Huang-Ge- nanovesicle) released
from both mouse and human breast tumor cells is enriched with RNAs. Tumor-derived HG-NVs are more
potent in promoting tumor progression than exosomes. Molecules predominantly present in breast tumor HG-
NVs have been identified and characterized. This discovery may have implications in advancing both
microvesicle biology research and clinical management including potential useas a biomarker, (2). Exosomes
released from non-tumor cells play a role in: (a) adipose tissue exosome-like vesicles mediating activation of
macrophage-induced insulin resistance (Diabetes. 2009 Nov;58(11):2498-505); (b) we also found that
intestinal mucus-derived exosomes mediate activation of Wnt/β-catenin signaling and play a role in induction
of liver NKT cell anergy (Hepatology, 2013 57(3):1250-61); and (c) intestinal mucus‐derived exosomes carry
prostaglandin E2 and suppress activation of liver NKT cells (J Immunol, 2013, 190(7):3579-89); (3). Exosome-
like nanoparticles from edible plants have an effect and therapeutic application on mammalian cells: (a) we
used mouse models to show that interspecies communication between plant and mouse gut host cells through
edible plant derived exosome‐like nanoparticles by inducing expression of genes for anti-inflammation
cytokines, antioxidation, and activation of Wnt signaling, wh...

## Key facts

- **NIH application ID:** 9899084
- **Project number:** 5IK6BX004199-03
- **Recipient organization:** LOUISVILLE VA MEDICAL MEDICAL CENTER
- **Principal Investigator:** HUANG-GE ZHANG
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899084

## Citation

> US National Institutes of Health, RePORTER application 9899084, BLR&D Research Career Scientist Award application (5IK6BX004199-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9899084. Licensed CC0.

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