Functional significance of hox genes in the epididymis

丹妮拉·邦加德纳博士致力于学术事业。她的目标是成为一名独立研究者，专注于生殖医学的基础研究。她目前的培训拓宽了她在生殖道细胞和分子生理学方面的知识。KO8将为她提供一个独特的机会，让她学习更先进的分子和细胞生物学方法，并在实验计划和关键数据分析方面变得更加熟练和有经验。泌尿外科致力于候选人的研究发展，并致力于确保保护研究时间。赞助商的生产实验室、弗吉尼亚大学的分子和细胞核心设施，以及与弗吉尼亚大学神经科学系的H. Scrable博士和s. Zeitlin博士的合作，为学习新的研究技术和解决科学问题的方法提供了良好的环境。重要的是，候选人咨询委员会由具有相关但不同专业领域的知名研究者组成，并强烈支持该项目。此外，B. Hinton博士（弗吉尼亚大学细胞生物学系）和M. Wilkinson博士（德克萨斯州休斯顿安德森癌症中心免疫学系）的专业知识将为候选人成为独立研究者的目标提供额外的支持。本研究的长期目标是发现附睾节段功能发展和维持的机制。精子在附睾中的成熟需要上皮基因产物以特定区域的模式表达。我们的假设是，hox基因是这一过程的主要调节者。众所周知，这些基因在胚胎的片段模式中起着至关重要的作用，但这些基因在成人中的功能尚不清楚。具体来说，建议开发内源性hoxa-11基因的条件突变。假设hoxa-11的下调通路包括Meis 1作为dna结合辅助因子和L1-CAM作为潜在靶点。我们将分析该通路中每个参与者的基因和蛋白表达模式。所得到的数据将作为基线来检验hoxa-11的时间调节影响发育的关键时期和成人附睾功能的假设。最后，我们将研究特定的5' hox基因可以与dna结合因子一起反激活特定的下游靶标的假设。广泛的现代研究技术将被使用，包括最先进的体内实验。这项研究结果将为理解某些形式的男性不育和某些儿科泌尿系统发育不良的重要基本生物学过程提供基础信息。

Dr. Daniela Bomgardner is committed to an academic career. , focusing on basic research in reproductive medicine with the goal of being an independent investigator. Her current training has broadened her knowledge in cellular and molecular physiology of the reproductive tract. The KO8 will provide a unique opportunity for her to learn more advanced methods in molecular and cellular biology and to become more proficient and experienced in experimental planning and critical data analysis. The Department of Urology is dedicated to the candidate's research development and is committed to ensure protected time for research. The combination of the sponsors productive laboratory, the molecular and cellular core facilities at UVA, and the collaboration with Dr.'s H. Scrable and S. Zeitlin (Dept. Neuro-science, UVA) provides and excellent environment for learning new research techniques and approaches to scientific problems. Importantly, the candidates advisory committee, composed of established investigator with pertinent but diverse areas of expertise, and is strongly supportive of this project. Moreover, the expertise of Dr. B. Hinton (Dept. of Cell Biology, UVA) and Dr. M. Wilkinson (Dept. of Immunology, M.D. Anderson Cancer Center, Houston, TX) will provide additional support for the candidate's goal of becoming an independent investigator. The long-term objective of this proposal is to discover the mechanism underlying the development and maintenance of segmental function in the epididymis. Sperm maturation in the epididymis requires epithelial gene products expressed in a region-specific pattern. Our hypothesis is that hox genes are master regulators of this process. These genes are known to be crucial in segmental patterning of the embryo, but adult function of these genes is unknown. Specifically, it is proposed to develop a conditional mutation of the endogenous hoxa-11 gene. It is hypothesized that the down-regulation pathway of hoxa-11 includes Meis 1 as a DNA-binding cofactor and L1-CAM as a potential target. The gene and protein expression pattern of each participant in this pathway will be analyzed. The resulting data will be used as a baseline to test the hypothesis that temporal regulation of hoxa-11 influences critical periods in development and adult epididymal function. Finally, the hypothesis, that specific 5' hox genes can transactivated particular downstream targets together with DNA-binding factors will be investigated. A broad spectrum of modern research techniques will be used including state-of- the-art in vivo experiments. Findings from this proposal will provide fundamental information for the understanding of basic biological processes important in certain forms of male infertility and in certain urological dysplasias in pediatric urology.