Functional significance of hox genes in the epididymis

Daniela Bomgaret博士致力于学术生涯。，专注于生殖医学的基础研究，目标是成为一名独立的研究者。 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。KO 8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，并在实验规划和关键数据分析方面变得更加精通和经验丰富。泌尿外科系致力于候选人的研究开发，并致力于确保研究时间受到保护。赞助商生产实验室，分子和细胞的核心设施在弗吉尼亚大学的组合，并与博士合作。的H. Scramble和S. Zeitlin（部门）神经科学，UVA）提供了一个良好的环境，学习新的研究技术和方法的科学问题。重要的是，候选人咨询委员会由具有相关但不同领域专门知识的知名调查员组成，并大力支持这一项目。此外，B博士的专业知识。欣顿（Dept.细胞生物学，UVA）和M.威尔金森（部门免疫学，医学博士安德森癌症中心，休斯顿，得克萨斯州）将提供额外的支持，候选人的目标，成为一个独立的研究者。本研究的长期目标是探索附睾节段性功能发育和维持的机制。精子在附睾中的成熟需要以区域特异性模式表达的上皮基因产物。我们的假设是hox基因是这一过程的主要调节者。已知这些基因在胚胎的节段模式中至关重要，但这些基因的成年功能尚不清楚。具体而言，建议开发内源性hoxa-11基因的条件突变。推测hoxa-11的下调途径包括作为DNA结合辅因子的Meis 1和作为潜在靶点的L1-CAM。将分析该途径中每个参与者的基因和蛋白质表达模式。由此产生的数据将被用作基线，以测试的假设，hoxa-11的时间调节影响发育和成人附睾功能的关键时期。最后，将研究特定的5' hox基因与DNA结合因子一起反式激活特定下游靶点的假设。将使用广泛的现代研究技术，包括最先进的体内实验。本研究结果将为理解某些类型的男性不育症和小儿泌尿系统发育不良的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.