# Thyroid Hormone Signaling in Human Hepatocytes

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $658,627

## Abstract

Project Summary
Thyroid hormone is a critical mediator of development and physiologic function in adulthood. It acts on
every cell type through both genomic and non-genomic mechanisms that have not been clearly defined
in humans. Much of our insight into thyroid hormone action comes from mouse genetic models which
appear to mimic human physiology given the conservation of the hypothalamic-pituitary thyroid axis. In
addition, human diseases, such as resistance to thyroid hormone, have validated the use of mouse
models but major question remain in context of cell specificity and unique paradigms that may occur in
human cell types. Work in human systems has been extremely limited because of the lack of models that
are thyroid hormone responsive. To get around this and begin to understand thyroid hormone action in
humans we have developed human hepatocytes from induced pluripotent stem cells (iPSCs) that are
highly TH responsive. Furthermore, using this unique model and gene editing techniques we can also
model human disease at the cellular level. To gain further insight into human thyroid hormone action we
propose three specific aims. In the first Aim we will determine the role of thyroid hormone receptor
isoforms both in context of physiologic pathways engaged and genomic targets engaged. In the second
Aim we will use our human hepatocyte model along with mouse genetic models to understand the role of
thyroid hormone signaling in the regulation of metabolic liver disease in response to dietary challenges.
Finally, in the third Aim we will use the CRISPR-Cas9 system to develop human disease models of
thyroid hormone signaling, to both identify novel therapeutic pathways but also to aid in understanding
the phenotype present in patients. Together completion of these Aims will provide key insight into how
thyroid hormone signal in human cells both in context of normal physiology but also in disease states and
open up new avenues to target these pathways in the treatment of metabolic disease.

## Key facts

- **NIH application ID:** 10087920
- **Project number:** 5R01DK117940-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** ANTHONY N HOLLENBERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $658,627
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10087920

## Citation

> US National Institutes of Health, RePORTER application 10087920, Thyroid Hormone Signaling in Human Hepatocytes (5R01DK117940-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10087920. Licensed CC0.

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