The long-term goal of this career development grant is to obtain and maintain a faculty position and research career in nutrition science with a focus on retinoids in skin and hair and their diseases. The immediate goal is to gain more knowledge about retinoids and their role in skin and hair physiology. The PI will reach these goals thru research, reading, attending seminars, attending and presenting at scientific meetings and publishing findings in the area of retinoids in skin and hair. This research project is focused on the regulation of endogenous retinoid metabolism and signaling during the normal hair cycle.
The specific aims are: to establish the localization and precise timing of retinoid metabolism in the hair follicle, sebaceous gland, and stem cells during the hair cycle; to determine if estrogen regulates retinoid metabolism in the cycling hair follicle; and to dissect the specific interactions between endogenous retinoic acid and Wnt signaling during the hair cycle. This is significant as several retinoids may be used to treat skin and hair disorders, but can have toxic side effects. Once we know where endogenous retinoids are being synthesized and how this synthesis is regulated we can begin to explore alternate treatments that have fewer side effects than current exogenous retinoid therapies. In addition, the normal hair cycle is an excellent physiological model of signaling pathways including retinoids.
The specific aims of this project will be accomplished thru a series of localization (protein and mRNA) studies of enzymes and binding proteins involved in retinoid metabolism in the hair follicle during natural and induced hair cycles. These studies will be extended by studies in mice. Topically treating mice with estrogen/ant estrogen and analyzing retinoid metabolism by immunohistochemistry will test estrogen regulation. The Lef1/Tcf transgenic mouse model (Tg(Fos-lacZ)34Efu/J; aka TOPGAL) will be treated with retinoids/inhibitors to determine the effects of retinoids in Wnt signaling during the hair cycle. This grant will provide the PI the opportunity to develop into an independent investigator.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
7K01AR052009-04
Application #
7537037
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Baker, Carl
Project Start
2005-07-01
Project End
2010-04-30
Budget Start
2008-03-01
Budget End
2008-04-30
Support Year
4
Fiscal Year
2007
Total Cost
$29,433
Indirect Cost
Name
Ohio State University
Department
Nutrition
Type
Other Domestic Higher Education
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Suo, Liye; Sundberg, John P; Everts, Helen B (2015) Dietary vitamin A regulates wingless-related MMTV integration site signaling to alter the hair cycle. Exp Biol Med (Maywood) 240:618-23
Duncan, F Jason; Silva, Kathleen A; Johnson, Charles J et al. (2013) Endogenous retinoids in the pathogenesis of alopecia areata. J Invest Dermatol 133:334-43
Sundberg, John P; Berndt, Annerose; Silva, Kathleen A et al. (2013) Alopecia areata: updates from the mouse perspective. J Investig Dermatol Symp Proc 16:S23-4
Everts, Helen B; Silva, Kathleen A; Montgomery, Shalise et al. (2013) Retinoid metabolism is altered in human and mouse cicatricial alopecia. J Invest Dermatol 133:325-33
Everts, Helen B (2012) Endogenous retinoids in the hair follicle and sebaceous gland. Biochim Biophys Acta 1821:222-9
Sundberg, J P; Taylor, D; Lorch, G et al. (2011) Primary follicular dystrophy with scarring dermatitis in C57BL/6 mouse substrains resembles central centrifugal cicatricial alopecia in humans. Vet Pathol 48:513-24
Everts, Helen B; Sundberg, John P; King Jr, Lloyd E et al. (2007) Immunolocalization of enzymes, binding proteins, and receptors sufficient for retinoic acid synthesis and signaling during the hair cycle. J Invest Dermatol 127:1593-604