# Engineering Human Brain Neurovascular Niche for Modeling Brain Diseases

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2022 · $220,625

## Abstract

Neurovascular unit (NVU) regulates efficient blood support and neuron functions in the brain. Its dysfunction or
breakdown is associated with a wide variety of neurological disorders including Alzheimer’s disease (AD) and
contribute to both initiating and exacerbating neuropathology. The underlying biological mechanisms, however,
remain insufficiently understood for the design of effective prevention or treatment. The progress in under-
standing these mechanisms has been limited, partially, due to the lack of appropriate and manipulatable pre-
clinical models for human brains that can recapitulate the complex cellular, biophysical and biochemical inter-
actions in human NVUs. To address these challenges, we have established an interdisciplinary team with ex-
pertise in microvascular engineering and vascular biology, and stem cell and neural biology to reconstruct hu-
man brain neurovascular niche for the understanding of NVU functions in both normal and diseased conditions.
We will exploit our synergistic capabilities to generate NVU through brain organoids technology with perfusable
brain microvessels. We will test the hypothesis that the vascular cells and complex neural circuits interact in
both time and space, that perfusable brain microvessels provide maturation cues to the neurons, whereas ge-
netic background of neurons influences the function of both vascular and neuron functions in the NVU. We will
interrogate the molecular and cellular changes of different cell types in vascularized brain organoid and how
this may be relevant to a disease state using AD patient derived iPSCs. Once successful, this project will de-
velop and exploit new vascular engineering technology, stem cell biology and bioinformatics to develop and
understand the structure and function of the neurovascular unit for modeling neurodegenerative diseases,
which further advances therapeutic development.

## Key facts

- **NIH application ID:** 10478162
- **Project number:** 5R21AG074373-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Jessica Elaine Young
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $220,625
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10478162

## Citation

> US National Institutes of Health, RePORTER application 10478162, Engineering Human Brain Neurovascular Niche for Modeling Brain Diseases (5R21AG074373-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10478162. Licensed CC0.

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