Vitamin A metabolism in hair cycle regulation
NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases
About This Grant
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.
Grant Summary
Vitamin A metabolism in hair cycle regulation is a NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases grant providing up to $475K for university, nonprofit, healthcare org. Applications are due 2029-07-31 (open). Check eligibility and apply with FindGrants.
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Up to $475K
2029-07-31
- 1Confirm your organization is eligible for Vitamin A metabolism in hair cycle regulation from NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases before the deadline.
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Vitamin A metabolism in hair cycle regulation: Frequently Asked Questions
Who is eligible for the Vitamin A metabolism in hair cycle regulation?
Vitamin A metabolism in hair cycle regulation is offered by NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Vitamin A metabolism in hair cycle regulation provide?
Vitamin A metabolism in hair cycle regulation provides up to $475K per award from NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Vitamin A metabolism in hair cycle regulation deadline?
Applications for Vitamin A metabolism in hair cycle regulation are due 2029-07-31 (open). Because deadlines can change, verify the date with the funder, NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Vitamin A metabolism in hair cycle regulation?
To apply for Vitamin A metabolism in hair cycle regulation, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases.