Tuesday, November 18, 2025 11/18/2025

Rosettes in Adrenal Development, Maintenance and Disease

Award Number: R01DK123694
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/19/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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Rosettes in Adrenal Development, Maintenance and Disease - The adrenal cortex continuously remodels in response to physiological cues, though the precise cellular and molecular mechanisms remain poorly understood. Our prior studies show that the adrenal cortex undergoes zonal transdifferentiation during postnatal development in the zona Glomerulosa (zG) gives rise to the zona Fasciculata (zF). This process involves formation and resolution of multicellular zG-rosettes via the adherens junction(AJ)-aCatenin complex. How these structures regulate aldosterone production and how dysregulation leads to disease is not known. Given that primary aldosteronism (PA), the most common form of endocrine hypertension, involves hyperplasic expansion of zG-rosettes, further study of the factors and signaling pathways involved in regulating zG development and maintenance is warranted. Utilizing a zG-specific b-catenin gain-of- function mouse model, we have shown that zG hyperplasia in PA is driven by a block in rosette resolution/transdifferentiation. In addition, this block involves up regulation of FGFR2 signaling, which is required for rosette formation during normal development. Further, we have found that rosettes act as a coordinating center for Ca2+ signaling, via the AJ-aCatenin complex, and subsequent aldosterone production. We also discovered that WNT2B, recently identified by GWAS analysis as a major risk allele for PA, is a novel regulator of aldosterone production and zG homeostasis. Based on our recent findings, it is increasing evident that further study of the role of AJs, rosettes and the signals that control them is necessary. Thus, we propose the following: Aim 1. Define how WNT2B mediates zG morphogenesis and function. Aim 2. Determine how a-Catenin and AJs mediate zG morphogenesis and function. Aim 3. Establish how FGFR2 regulates zG morphogenesis and function. These studies seek to understand the regulatory mechanisms that control zG function during postnatal development and maintenance. The successful completion of these studies will provide critical insights into the mechanisms that govern zG homeostasis and the initiation and progression of PA, which may lead to new targeted therapies for this disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $755,828 )
2025	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	7	6/24/2025	NON-COMPETING CONTINUATION	$755,828
2025	2023	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	2/12/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $755,828

Issue Date FY: 2024 ( Subtotal = $775,328 )
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	7/23/2024	COMPETING CONTINUATION	$775,328
														Subtotal = $775,328

Issue Date FY: 2023 ( Subtotal = $659,908 )
2023	2023	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	6/29/2023	NON-COMPETING CONTINUATION	$659,908
														Subtotal = $659,908

Issue Date FY: 2022 ( Subtotal = $659,908 )
2022	2022	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	7/1/2022	NON-COMPETING CONTINUATION	$659,908
														Subtotal = $659,908

Issue Date FY: 2021 ( Subtotal = $659,908 )
2021	2021	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	6/25/2021	NON-COMPETING CONTINUATION	$659,908
														Subtotal = $659,908

Issue Date FY: 2020 ( Subtotal = $659,908 )
2020	2020	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	8/21/2020	NON-COMPETING CONTINUATION	$659,908
														Subtotal = $659,908

Issue Date FY: 2019 ( Subtotal = $679,158 )
2019	2019	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/18/2019	NEW	$679,158
														Subtotal = $679,158

Grand Total All Awards = $4,849,946

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Rosettes in Adrenal Development, Maintenance and Disease

Award Number: R01DK123694

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/19/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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