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Vitamin A metabolism in hair cycle regulation

Award Number: R15AR085911
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2029

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Vitamin A metabolism in hair cycle regulation - 7. Project Summary/Abstract: Studying the hair cycle provides an in vivo model for studying stem cell regulation that can be easily accessed, manipulated, and visualized. Loss of hair follicle stem cells (HFSCs) leads to hair aging and hair loss, while aberrant regulation of these HFSCs contributes to cutaneous squamous cell carcinoma (cSCC). cSCC is costly to treat and leads to metastasis and death. Hair loss leads to significant stigmatization, low self-esteem, anxiety, and reduced quality of life, which are worse in women. HFSC quiescence is essential for their self- renewal. HFSC quiescence is greater in females than males. Estrogen regulates HFSC quiescence in a sex dependent manner. However, we do not understand the complete mechanisms for these sex differences. Retinoids are a family of vitamin A derived compounds, which includes vitamin A (retinol) and its active metabolite retinoic acid (RA). RA regulated HFSC quiescence dose-dependently in vitro. Importantly, our data shows that dietary vitamin A and loss of RA synthesis also regulates HFSCs in vivo. Retinoids prevented or worsened the development of cSCC and hair loss in humans and mouse models, but few of these studies examined an effect of sex. We and others found that sex hormones regulated expression of RA synthesis and signaling genes and RA responses in a sex dependent manner. RA, in turn, affects sex hormone synthesis and signaling, suggesting the existence of an interaction between sex hormones and RA signaling. The objectives in this application are to identify how sex hormones and exogenous retinoids alter endogenous RA synthesis within the HFSC niche to maintain HFSC quiescence and determine how this affects HFSCs and hair loss during aging. Our central hypothesis is that sex hormones regulate RA synthesis to maintain HFSC quiescence to prevent hair aging. The specific aims are to: 1) Identify the vitamin A metabolism and signaling cross talk with sex hormone signaling to maintain quiescent HFSCs in a sex dependent manner; and 2) Identify the role of Sdr16c5 and Sdr16c6 in hair aging in a sex dependent manner. The approach is to treat whole body Sdr16c5-/-/Sdr16c6-/- double knockout mice with sex hormone receptor agonists and antagonists and examine HFSC quiescence. We will also rescue these transgenic mice with synthetic retinoids. In addition, we will analyze hair cycling as these mice age. Understanding how sex hormones and vitamin A metabolism interact in a sex-dependent manner to regulate hair follicle stem cells in vivo is significant because it will lead to the development of alternative sex specific retinoid treatments with more specificity and fewer side effects than current retinoid therapies. Once we identify which vitamin A metabolism enzymes and RARs are involved, we can target therapies to regulate endogenous RA synthesis and/or specific RARs. The proposed research is innovative because it will identify how endogenous RA synthesis is regulated in a sex dependent manner using state of the art retinoid analysis technology.


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: 2026 ( Subtotal = $475,063 )
2026	2026	TEXAS WOMANS UNIVERSITY	304 ADMINISTRATION DRIVE	DENTON	TX	76204	DENTON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	7/28/2026	NEW	$475,063
														Subtotal = $475,063

Grand Total All Awards = $475,063

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Vitamin A metabolism in hair cycle regulation

Award Number: R15AR085911

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2029

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