# "Exploration of Human Parathyroid Cellular Organization and Function"

> **NIH NIH R21** · YALE UNIVERSITY · 2020 · $430,686

## Abstract

PROJECT SUMMARY
Hypoparathyroidism (HP) is a major toxicity of surgery for thyroid malignancy. Parathyroid (PT) glands are
endocrine organs critical for maintaining calcium homeostasis. The most common cause of HP is iatrogenic -
occurring after removal of the PT glands during dissection of the anterior and central neck compartment for the
treatment of thyroid (or parathyroid) cancer. It is estimated that 5-7% of patients develop HP following
thyroidectomy, and that the total number of adults with HP in the US is about 77,000. Some patients are
unable to maintain stable physiological levels of Ca2+ and can suffer severe consequences including muscle
cramping, tetany, and convulsions. The Krause laboratory is developing approaches for differentiation of
autologous cells into functional PT cells. Identification and characterization of human PT stem/progenitor cells
is critical for developing effective approaches for cell therapies for HP. The Krishnaswamy laboratory has
developed a novel computational tool, PHATE (Potential of Heat-diffusion for Affinity-based Transition
Embedding), which is able to capture intrinsic data geometry and denoise scRNA-seq data so that both local
and global structures are apparent without imposing assumptions on the form of the data. PHATE is
particularly powerful in analyzing differentiation data generated by dynamic processes where there is
continuous variability between data points and thus is an ideal tool with which to dissect the cellular
composition of complex tissues such as the PT gland. We hypothesize that the maintenance of the PT glands
relies on stem/progenitor cell compartments that reside within supportive niches. We propose to define these
cellular components and the maintenance mechanisms of PT tissue using scRNA-seq, PHATE, and functional
studies through two specific aims. In the first, we will obtain primary PT glands and perform scRNA-Seq, which
will then be analyzed with PHATE to reconstruct the cellular organization and the maintenance mechanisms of
human PT gland. In the second, we will determine the functionality within the PT glands of specific cell
populations determined by PHATE. Longterm in vivo function of PT cell subpopulations will be assessed by
transplantation into immunodeficient mice. The studies proposed will shed light on the composition and cellular
functions of different PT compartments, and will enhance our understanding of the homeostatic mechanisms
that maintain the functional epithelial compartments of normal PT glands. The insight obtained will enhance
understanding of the basic mechanisms of adult PT gland maintenance and regeneration, essential preclinical
knowledge for the development of novel cellular therapies to restore PT function to patients with
hypoparathyroidism.

## Key facts

- **NIH application ID:** 10044664
- **Project number:** 1R21CA240660-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Diane S Krause
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $430,686
- **Award type:** 1
- **Project period:** 2020-07-20 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10044664

## Citation

> US National Institutes of Health, RePORTER application 10044664, "Exploration of Human Parathyroid Cellular Organization and Function" (1R21CA240660-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10044664. Licensed CC0.

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