The role of prostaglandin d2 in hair follicle biology

该指导临床科学家职业奖（K 08）申请提出了一项为期5年的研究和培训计划，以将主要研究者转变为独立的RO 1资助的学术皮肤科医生。在同时强调临床和研究技能发展的同时，该补助金将允许主要研究者制定一个强大的研究计划和调查路线，以继续研究皮肤中的前列腺素生物学，重点是毛发生物学。科学建议的重点是产生PGDa的前列腺素合成酶L-PGDS。我们已经在小鼠（K14-COX 2转基因）和人（雄激素性脱发）中发现了PGDa水平升高与毛发小型化和皮脂腺增生表型的相关性。我们的假设是PGD 2介导这些效应。我们建议研究PGD 2信号改变的转基因和基因敲除小鼠，以建立因果关系和机制。最后，根据目前的文献，我们假设PGD 2介导的毛囊小型化和皮脂腺增生的机制是通过毛囊干细胞的命运从毛发角质形成细胞向皮脂细胞谱系的偏向。我们将通过使用毛囊干细胞谱系图谱来测试这一点。主要研究者是MSTP培训的MD-PhD，具有15年的生物医学研究经验，自2005年完成住院医师以来获得皮肤病学委员会认证。毛发生物学世界权威医学博士乔治·科特萨雷利斯和药理学系主任医学博士加勒特·菲茨杰拉德将担任主要研究者科学和临床发展的共同导师。Cotsarelis博士是毛囊中干细胞生态位的共同发现者，是国际公认的毛发疾病临床护理专家，也是众多博士后研究员的经验丰富的导师，其中许多人已经成为皮肤病学和毛发生物学的研究人员。Fitzgerald博士是前列腺素生物学方面的国际知名专家，也是转化医学研究所（ITMAT）的主任。这一跨学科的建议将利用两个建立和高度重视的医生科学家的专业知识，为主要研究者未来的独立性提供一个独特的利基。

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.