Kisspeptin Physiology in Human Reproduction

描述(申请人提供)：这项资助的目的是为以患者为导向的研究中的指导活动寻求资金支持，让年轻的受训者体验科学发现的兴奋。通过指导，这位申请者希望通过让他们体验到他们发现的新的生物和健康知识并将这些知识转化为患者的切实利益，例如更好的诊断策略或新的临床疗法，来培养下一代临床医生研究人员。为了支持这种培训工作，这笔赠款将为申请者提供财政资源，使她能够维持自己的研究计划，同时腾出时间进行指导活动。这些指导活动包括教授学员如何建立假设、设计方案、实现患者安全的最高标准、解决监管问题、编写手稿、撰写补助金以及实现他们的职业目标。受训者将在申请者的生殖遗传学和生理学研究计划内工作。申请人发现，Kispeptin-Gpr54信号通路的突变导致哺乳动物物种中没有青春期发育和性腺激素减退。她现在正在使用Kispeptin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先天性促性腺激素释放激素缺乏的患者，他们已经进行了广泛的表型和基因分型。Kispeptin(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的患者提供另一种治疗干预途径。考虑到这一途径的转移抑制特性，生殖癌患者可能会获得额外的好处。综上所述，这些项目和申请人的指导将提供一个强大的计划，培训新的临床研究人员以患者为中心的研究。

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.