# Diversity Supplement - Effects of microgravity on the structure and function of proximal and distal tubule MPS

> **NIH NIH UH3** · UNIVERSITY OF WASHINGTON · 2020 · $78,932

## Abstract

ABSTRACT
The goal of the parent grant is to evaluate the effects of microgravity on kidney tubule structure and function.
These discoveries will improve public health by informing novel strategies for the design and development of
better treatments for proteinuric kidney disease, osteoporosis, and kidney stones in the general public.
Kidney dysfunction can precipitate serious medical conditions including proteinuria, osteoporosis, and formation
of kidney stones. These conditions occur more frequently, and progress faster, in crewmembers stationed on
the International Space Station. Current static models of the proximal and distal tubules are unable to recapitulate
cellular functions including protein reabsorption via megalin, vitamin D metabolic bioactivation, and micro-crystal
mediated injury response. We have developed a microphysiologic model of the proximal tubule using primary
proximal tubule epithelial cells (PTECs) that has successfully demonstrated physiologic cellular
structure/polarization, transport of glucose and drug substrates, bioactivation of inactive 25- hydroxy vitamin D
to 1α,25-dihydroxyvitamin D (which promotes beneficial bone remodeling), and physiologic injury response to
toxic exposure. We will expand this technology to develop a distal tubule epithelial cell model (DTEC) which will
be used to explore the pathophysiologic response to oxalate microcrystals. Studying the proximal and distal
tubules in the microgravity environment of the International Space Station presents the unique opportunity to
observe accelerated disease processes (proteinuria, osteoporosis, kidney stones), which will facilitate the
discovery of factors that contribute to the development and progression of kidney diseases that cannot be
observed on a conventional time scale. Therefore, the aims of this project are: to determine the effects of
microgravity on the polarized structural aspects (eg., ion and solute transporters) of the kidney proximal and
distal tubule epithelium in a 3D microphysiological system, to determine if Vitamin D bioactivation/homeostasis
within the kidney proximal tubule is compromised in response to extended exposure to microgravity, and to
create a disease-state models of proximal tubule proteinuria and distal tubule kidney stone formation to evaluate
the harmful or adaptive modulating effects of microgravity. A better understanding of the factors and pathways
that underlie proper cellular structure and the development and progression of kidney diseases will uncover
novel therapeutic targets that can be used in the development of pharmacologic agents that can improve the
health of Space Station crewmembers as well as the health of the general public by preventing or reversing
proteinuria, osteoporosis, and kidney stones.
We have requested support under the Diversity Supplement mechanism for Mr. Kendan Jones-Isaac, a student
in the Pharmaceutics PhD program at the University of Washington. Mr. Jones-Isaac has been an active and
...

## Key facts

- **NIH application ID:** 9946987
- **Project number:** 3UH3TR002178-04S1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Jonathan Himmelfarb
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $78,932
- **Award type:** 3
- **Project period:** 2017-06-15 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9946987

## Citation

> US National Institutes of Health, RePORTER application 9946987, Diversity Supplement - Effects of microgravity on the structure and function of proximal and distal tubule MPS (3UH3TR002178-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9946987. Licensed CC0.

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