The role of prostaglandin d2 in hair follicle biology

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DESCRIPTION (provided by applicant): This mentored clinical scientist career award (K08) application proposes a 5 year research and training program to transition the principal investigator towards an independent RO1 funded academic dermatologist. While concurrently emphasizing clinical and research skill development, this grant will allow the principal investigator to develop a robust research program and line of inquiry for continued study of prostaglandin biology in skin with an emphasis on hair biology. The scientific proposal focuses on the prostaglandin synthase L-PGDS which produces PGDa. We have discovered correlations both in mouse (K14-COX2 transgenic) and man (androgenetic alopecia) of elevations in PGDa levels and the phenotype of hair miniaturization and sebaceous hyperplasia. Our hypothesis is that PGD2 mediates these effects. We propose to investigate transgenic and knockout mice with altered PGD2 signaling to establish causality and mechanism. Finally, based on current literature, we hypothesize that the mechanism of PGD2 mediated hair follicle miniaturization and sebaceous hyperplasia is through bias of hair follicle stem cell fate from hair keratinocyte towards sebocyte lineage. We will test this through the use of lineage mapping of hair follicle stem cells. The principal investigator is an MSTP trained MD-PhD with 15 years experience in biomedical research and is board certified in dermatology since completion of a residency in 2005. George Cotsarelis, MD, a world authority on hair biology, and Garret Fitzgerald MD, chairman of the Department of Pharmacology, will serve as co-mentors for the principal investigator's scientific and clinical development. Dr. Cotsarelis was co-discoverer of the stem cell niche in the hair follicle, an internationally recognized expert on the clinical care of hair disorders and an experienced mentor of numerous postdoctoral fellows, many of whom have become established researchers in dermatology and hair biology. Dr. Fitzgerald is an internationally renowned expert in prostaglandin biology who is also the director of the translational medicine institute (ITMAT). This interdisciplinary proposal will capitalize on the expertise of two established and highly regarded physician scientists yielding a unique niche for the future independence of the principal investigator.