Hyaluronic Acid with CD44, Estrogen and Progesterone Influence the Development of Endometrium to Endometriosis

项目概要/摘要： 这个指导以患者为导向的研究职业发展奖（K23）将提供一个有前途的早期- 阶段研究员，博士Knudtson，与必要的知识和技能，成为一个独立的临床- 子宫内膜异位症的治疗方法克努森博士的兴趣在于将新颖的基础科学发现 透明质酸（HA）通路、雌激素和 孕激素在发育中的作用。Knudtson博士将积极参与各种 在前瞻性非干预性研究的临床研究学习方面的培训活动， 通过统计分析了解临床试验，包括研究设计。她会运用她的知识 和技能学到的执行一个创新的研究项目的发展子宫内膜异位症， 月经期子宫内膜及HA/CD 44、雌激素和孕激素的作用。培训活动涉及 Knudtson博士的知识和技能的差距，研究项目解决了一个重大差距， 了解子宫内膜异位症 子宫内膜异位症由月经期子宫内膜发展而来，是疼痛和不孕的原因。存在差异 子宫内膜异位症妇女和非子宫内膜异位症妇女月经期子宫内膜。这项拟议研究的具体目标是 目的：（1）研究口服避孕药（OCPs）对绝经后妇女血透明质酸酶的影响。 与无子宫内膜异位症的妇女相比，子宫内膜异位症;（2）为了确定CD 44变体的作用， HA的主要受体，在月经期子宫内膜与子宫内膜异位症病变。这些研究将继续 前瞻性、非干预性试验，并纳入转化和临床研究。培训的目的 包括：（1）开发使用人体组织的前瞻性临床研究的专业知识;（2）获得结构化的 通过临床研究-转化科学硕士进行临床研究培训。博士 Knudtson的主要导师是Robert Schenken博士，他是一位医生科学家，拥有世界知名的专业知识， 子宫内膜异位症她的共同导师是Randal罗宾逊博士，他是一位具有临床研究专长的内科科学家。的 咨询委员会由Rajeshwar Tekmal博士（翻译研究员）、Joel Tsevat博士（医生） 科学家与以前的K学者）和乔纳森Gelfond博士（生物统计学家）。Knudtson博士的独特优势 包括转化研究能力和经验，具有临床知识并希望成为临床 调查员导师和咨询委员会所代表的综合专业知识和经验将 使她能够实现所提出的职业目标，并成为一名独立的医生科学家，专注于 子宫内膜异位症的患者导向研究

Project Summary/Abstract: This Mentored Patient-Oriented Research Career Development Award (K23) will provide a promising early- stage investigator, Dr. Knudtson, with the knowledge and skills requisite to become an independent clinical- investigator in the field of endometriosis. Dr. Knudtson's interest is in applying novel, basic science findings into translational clinical research on the effects of the hyaluronic acid (HA) pathway, estrogen and progesterone in the development of the endometriotic lesion. Dr. Knudtson will actively participate in a variety of training activities in the learning of clinical investigation for prospective non-interventional studies and understanding of clinical trials including study design through statistical analysis. She will apply her knowledge and skills learned to the execution of an innovative research project on development of endometriosis from menstrual endometrium and the roles of HA/CD44, estrogen and progesterone. The training activities address gaps in Dr. Knudtson's knowledge and skills, and the research project addresses a significant gap in understanding of endometriosis. Endometriosis develops from menstrual endometrium and is a cause of pain and infertility. Differences exist in menstrual endometrium from women with and without endometriosis. The specific aims of this proposed study are: (1) To determine the effect of oral contraceptive pills (OCPs) on the HA enzymes in women with endometriosis compared to women without endometriosis; (2) To establish the role of the CD44 variants, the primary receptor for HA, in menstrual endometrium versus the endometriosis lesion. These studies will pursue prospective, non-interventional trials and incorporate translational and clinical research. The training aims consist of: (1) developing expertise in prospective clinical studies using human tissues; (2) obtaining structured clinical research training through a Masters of Science in Clinical Investigation-Translational Science. Dr. Knudtson's primary mentor is Dr. Robert Schenken, a physician scientist, with a world renowned expertise in endometriosis. Her co-mentor is Dr. Randal Robinson, a physician scientist with expertise in clinical studies. The advising committee consists of Dr. Rajeshwar Tekmal (translational researcher), Dr. Joel Tsevat (physician scientist with previous K scholars), and Dr. Jonathan Gelfond (biostatistician). Dr. Knudtson's unique strengths include aptitude and experience in translational research, with clinical knowledge and desire to become a clinical investigator. The combined expertise and experience represented by the mentors and advising committee will enable her to achieve the career goals proposed and to become an independent physician scientist focused on patient oriented research in endometriosis.