Kisspeptin Physiology in Human Reproduction

描述（由申请人提供）：本基金旨在资助以病人为导向的研究指导活动，让年轻的受训者体验科学发现的兴奋。通过指导，申请人希望培养下一代临床研究人员，让他们体验到将他们发现的新的生物学和健康知识转化为患者切实利益的美妙回报，例如更好的诊断策略或新的临床疗法。为了支持这样的培训工作，这笔资助将为申请人提供经济资源，以便她可以在腾出时间进行指导活动的同时保持自己的研究项目。这些指导活动包括教授受训者如何建立假设、设计方案、达到患者安全的最高标准、解决监管问题、撰写手稿、撰写拨款以及实现他们的职业目标。受训者将在申请人的生殖遗传学和生理学研究项目中工作。申请人发现kisspeptin-GPR54信号通路的突变导致哺乳动物缺乏青春期发育和促性腺功能低下。她现在使用kisspeptin管理作为人类生殖生物学中GnRH神经元完整性的第一个直接探针。研究方案将包括健康志愿者和已经广泛进行表型和基因分型的先天性GnRH缺陷患者。Kisspeptin（或类似化合物）可能为生殖癌、子宫内膜异位症、不孕症和青春期时间异常患者提供另一种治疗干预途径。考虑到该途径的转移抑制特性，生殖癌患者可能会获得额外的益处。综上所述，这些项目和申请人的指导将为培训新的临床研究人员提供一个强有力的计划，以患者为导向的研究。

DESCRIPTION (provided by applicant): The purpose of this grant is to seek financial support for mentoring activities in patient -oriented research to allow young trainees to experience the excitement of scientific discovery. By mentoring, this applicant hopes to build the next generation of clinician investigators by having them experience the wonderful rewards of taking new biologic and health knowledge they have discovered and translating that knowledge into tangible benefits for patients, such as better diagnostic strategies or novel clinical therapies. In order to support such training efforts, this grant would provide financial resources for the applicant, so that she could maintain her own research program while freeing up time for mentoring activities. These mentoring activities involve teaching trainees how to build hypotheses, design protocols, achieve the highest standards of patient safety, address regulatory issues, develop manuscripts, write grants, and meet their career goals. The trainees will work within the applicant's research program in reproductive genetics and physiology. The applicant discovered that mutations in the kisspeptin-GPR54 signaling pathway result in an absence of pubertal development and hypogonadotropic hypogonadism across mammalian species. She is now using kisspeptin administration as the first direct probe of GnRH neuronal integrity in human reproductive biology. Study protocols will include healthy volunteers and patients with congenital GnRH deficiencies who have already been extensively phenotyped and genotyped. Kisspeptin (or analogous compounds) may provide another avenue for therapeutic intervention for patients with reproductive cancers, endometriosis, infertility, and abnormalities of pubertal timing. Patients with reproductive cancers may derive additional benefits given the metastasis suppressor properties of this pathway. Taken together, these projects and the applicant's mentoring will provide a strong program for training new clinical investigators in patient-oriented research.