# Integrated systems biology of the pituitary

> **NIH NIH R56** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $169,000

## Abstract

The pituitary is critical to all endocrine systems. In recent work, we have optimized methods to generate high
quality single cell omics datasets using individual frozen mouse pituitaries. Together with the accompanying
advances in single cell bioinformatic analysis platforms developed by us and our collaborators, these
capabilities and results provide the foundation to achieve comprehensive insight into the layered epigenetic
regulatory mechanisms underlying cell physiology and disease processes, spanning from single genes
resolved in detail in each cell type to the global gene regulatory responses across the diverse cells of the
pituitary. Results to date suggest an expected plasticity of cell state and cell type across pituitary cell systems
during the reproductive cycle and during development of an important pathophysiological condition, primary
hypothyroidism. We will study the overall hypothesis that a profound and previously unappreciated plasticity of
mature pituitary cell types underlies normal physiology and disease. Because regulation of alternative gene
splice site usage is important in pituitary cell type function, we will incorporate comprehensive study of the
dynamics of pituitary cell type alternative splice usage, alternative promoter usage and lncRNAs into our single
cell platforms using single cell long read methods. We propose to test hypotheses identified in single cell in
vivo datasets for the signaling and epigenetic mechanisms regulating Fshb, a key
hypothalamic-pituitary-gonadal axis regulator gene that is transcriptionally controlled (Aim 1). We will elucidate
the coordination of regulatory processes across multiple pituitary endocrine cell types underlying pituitary
plasticity during the reproductive cycle, using both single cell short read and long read and refined analysis
methods (Aim 2). Focusing on a pituitary disease that causes transdifferentation among pituitary cell types, we
will apply these single cell methods to delineate the multi-cell type mechanisms mediating pituitary adaptations
to primary hypothyroidism in mouse models and investigate the underlying mechanisms for these processes
(Aim 3). This research will address key questions relevant to normal physiological processes and disease and
provide data and methods to advance research for both endocrine researchers and the broader community.

## Key facts

- **NIH application ID:** 11091386
- **Project number:** 2R56DK046943-28
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** STUART C. SEALFON
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $169,000
- **Award type:** 2
- **Project period:** 1993-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11091386

## Citation

> US National Institutes of Health, RePORTER application 11091386, Integrated systems biology of the pituitary (2R56DK046943-28). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11091386. Licensed CC0.

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