# Mechanisms of Adrenal Differentiation

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $483,012

## Abstract

ABSTRACT
The long-range objective of our laboratory is to understand the cellular and molecular mechanisms by which
signaling pathways and downstream transcription factors coordinate the specification of adrenocortical cells
within the adrenal gland. Our goal during this grant cycle is to define mechanisms by which the transcription
factor HHEX specifies identity and function of cells in the inner zona fasciculata (zF). Based on our preliminary
data, we hypothesize that HHEX is a requisite factor for the enhanced glucocorticoid secretion during chronic
stress adaptations; together with androgen-driven lipid catabolism and tissue renewal in the adrenal zF.
To this end, our strategy and specific aims for this proposal are designed to 1) Define the intracellular
mechanisms by which HHEX regulates the identity and function of the glucocorticoid-producing inner zF cells
that are enriched during chronic stress (Abcb1b+ inner zF population), 2) Determine the contribution of HHEX to
transcriptional programs the underly dynamic androgen-driven sterol flux in the adrenal zF and, 3) Characterize
the role of HHEX in adrenal zF tissue renewal.
The studies proposed here will provide fundamental knowledge of cellular heterogeneity in the adrenal cortex,
specifically the cell populations producing glucocorticoids during stress adaptation, and will provide the
groundwork for future clinical insights and therapeutic treatments for patients with chronic diseases of adrenal
insufficiency and stress-related disorders.

## Key facts

- **NIH application ID:** 10876629
- **Project number:** 2R01DK062027-18A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** GARY D. HAMMER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $483,012
- **Award type:** 2
- **Project period:** 2004-02-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876629

## Citation

> US National Institutes of Health, RePORTER application 10876629, Mechanisms of Adrenal Differentiation (2R01DK062027-18A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10876629. Licensed CC0.

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