The role of prostaglandin d2 in hair follicle biology

描述(由申请者提供)：这项指导临床科学家职业生涯奖(K08)的申请提出了一个为期5年的研究和培训计划，以将首席研究员转变为一名独立的RO1资助的学术皮肤科医生。在强调临床和研究技能发展的同时，这笔赠款将使首席研究员能够制定一项强有力的研究计划和研究路线，以继续研究皮肤中的前列腺素生物学，重点是头发生物学。这项科学提案的重点是前列腺素合成酶L-前列腺素D-D，它能产生前列腺素DA。我们发现，在小鼠(K14-COX2转基因)和人(雄激素性脱发)中，PGDa水平的升高与毛发小型化和皮脂腺增生的表型有关。我们的假设是，PGD2介导了这些效应。我们建议对PGD2信号改变的转基因和基因敲除小鼠进行研究，以建立因果关系和机制。最后，在现有文献的基础上，我们假设PGD2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从毛发角质形成细胞向皮脂细胞系的偏向所致。我们将通过使用毛囊干细胞的谱系图谱来测试这一点。首席研究员是MSTP培训的医学博士，在生物医学研究方面有15年的经验，自2005年完成住院医师资格以来，已获得皮肤病委员会认证。世界毛发生物学权威George Cotsarelis医学博士和药理学系主任Garret Fitzgerald医学博士将共同指导首席研究员的科学和临床发展。科萨雷利斯博士是毛囊干细胞利基的共同发现者之一，是国际公认的毛发疾病临床护理专家，也是许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和毛发生物学方面的知名研究人员。菲茨杰拉德博士是国际知名的前列腺素生物学专家，也是转化医学研究所(ITMAT)的主任。这项跨学科的建议将利用两位久负盛名的内科科学家的专业知识，为未来首席研究员的独立性创造独特的利基。

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.