# Novel noninvasive high-resolution in vivo imaging platform to study the thyroid gland physiology

> **NIH NIH R21** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2021 · $191,875

## Abstract

Project Summary/Abstract
All tissues of a living organism rely on normal thyroid hormone levels to develop and function properly. Millions
of people world-wide suffer from thyroid dysfunction (TD). TD incidence is 4-10% in the general population and
is considerably higher in people with metabolic diseases. Despite the central role that thyroid gland plays in
human physiology, most of what we know about thyroid cell biology, control of thyroid follicular cell growth,
vasculature adaptation and endocrine interactions has been derived from histological assessments and in vitro
studies that limit translation to the in vivo environment. Remarkably, these in vitro set-ups do not replicate the
basic functional unit of the thyroid, particularly the three-dimensional angio-follicular unit. Therefore, in vivo
studies of thyroid gland physiology and pathophysiology are hindered by the lack of approaches in which the
thyroid gland can be assessed in its natural architecture. The long-term goal of my research is to understand
the cell biology of the thyroid gland in the living organism. The strength of the present application relies on my
preliminary data of a robust technological platform that I developed in my laboratory. This novel approach
allows noninvasive real-time in vivo imaging of the mouse and human follicular cell. The technology is based
on transplantation of the mouse and human thyroid fragments into the mouse eye, which engrafts and
becomes revascularized; it permits the analysis of longitudinal changes in thyroid graft size, blood flow and
vessel diameters, with three-dimensional in vivo images of the thyroid angio-follicular unit. My hypothesis is
that mouse and human thyroid gland transplanted into the mouse anterior chamber of the eye resembles the
normal cellular structure of the thyroid and recapitulate the responses/adaptations to iodine deficiency and
thyrotoxicosis. To test my hypothesis, I will pursue two specific aims: 1) obtain unique in vivo intracellular
physiological measurements of the angio-follicular unit and its response to physiological stimuli and 2) gain in
vivo insights into the adaptation of the human and mouse angio-follicular unit and its cellular components to
iodine deficiency and thyrotoxicosis. I will study mice transplanted with mouse and human thyroid specimens
and manipulate different endocrine stimuli. Transgenic mouse models will allow me to demonstrate for the first
time thyrocytes activation in vivo. I will challenge the system by hyperactivating the thyroid gland with
experimental iodine deficiency. The responses to thyrotoxicosis (increased levels of thyroid hormone) will also
be assessed. This innovative platform will overcome a major technical roadblock by allowing the visualization
and measurement of dynamic properties of the thyroid gland biology in vivo. At their successful completion,
my studies will enhance our knowledge of the in vivo mechanisms of vasculature adaptation and thyroid
follicular cell...

## Key facts

- **NIH application ID:** 10220963
- **Project number:** 5R21DK125903-02
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Joao Pedro Saar Werneck de Castro
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $191,875
- **Award type:** 5
- **Project period:** 2020-07-21 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220963

## Citation

> US National Institutes of Health, RePORTER application 10220963, Novel noninvasive high-resolution in vivo imaging platform to study the thyroid gland physiology (5R21DK125903-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10220963. Licensed CC0.

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