CDA: Isolation and Characterization Testis Stem Cells; Influence of GDNF

描述（由申请人提供）：本职业发展计划将确保玛丽-克劳德·霍夫曼博士在代顿大学生物系作为一名独立研究科学家取得成功。Hofmann博士的一般兴趣领域是精原干细胞（ssc）的生物学，即单个精原细胞。人们对单精原细胞非常感兴趣，因为它们对于理解细胞自我更新与分化的基本机制、生殖功能障碍的治疗以及睾丸癌（特别是精原细胞瘤）的病因学具有重要意义。然而，对这些细胞的生物学研究受到严重阻碍，因为它们数量少，没有独特的标记存在，并且很难从其他更成熟的精原细胞中物理分离它们。霍夫曼博士的团队最近开发了一种方法，可以分离出ssc的纯群体，并开始在体外研究它们的行为。利用微阵列，他们还分析了ssc在胶质细胞系衍生神经营养因子（GDNF）存在下的转录程序，GDNF是一种由支持细胞产生的生长因子。Hofmann博士的研究目标之一是阐明GDNF诱导的促进ssc更新和分化的信号通路。在第一个目的中，将分离单个精原细胞并通过生殖细胞移植评估其克隆潜能。在第二个目标中，他们将确定哪些信号通路是由GDNF诱导的，导致单个精原细胞自我更新或分化。在第三个目标中，他们将研究GDNF如何与其他生长因子/受体相互作用以促进自我更新或分化。这项工作将扩大对单精原细胞功能特征的认识，并有助于更好地了解驱动精子发生第一步的分子机制。特别是，生长因子GDNF在调节自我更新和/或分化中的作用将被阐明。这份职业发展计划将帮助霍夫曼博士完成她的目标。具体来说，这将使她从繁重的教学中解脱出来，从而使她能够全身心地投入到研究中，提高她在生物医学科学和技术特定领域的技能。此外，霍夫曼博士将不被要求在管理委员会任职，并免除本科生的指导职责。在代顿大学，生物系、艺术与科学学院和研究生院将为霍夫曼博士的研究生涯发展提供一个支持性的环境。代顿大学最近投入了大量资源来促进跨学科生物科学和工程研究，霍夫曼博士是我们核心研究小组的重要成员。这个奖项将使她能够进一步与我们大学的其他部门以及其他机构合作。

DESCRIPTION (provided by applicant): This Career Development Plan will ensure Dr. Marie-Claude Hofmann's success as an independent research scientist in the Department of Biology, University of Dayton. Dr. Hofmann's general area of interest is the biology of spermatogonial stem cells (SSCs), the Asingle spermatogonia. There is great interest in the Asingle spermatogonia because of their importance for understanding basic mechanisms of cell self-renewal versus differentiation, for the treatment of reproductive dysfunction, and for the understanding of the etiology of testicular cancer, in particular seminoma. However, studies on the biology of these cells have been severely hampered because their number is low, no unique marker exists and it has been difficult to physically separate them from the other more mature spermatogonia. Dr. Hofmann's team recently developed a method that allows the isolation of pure populations of SSCs, and has started to study their behavior in vitro. Using microarrays, they also have analyzed the transcriptional program of SSCs in the presence of glial cell line derived neurotrophic factor (GDNF), a growth factor produced by Sertoli cells. One of Dr. Hofmann's research objectives is to elucidate the signaling pathways induced by GDNF that promote SSCs renewal and differentiation. In the first aim, Asingle spermatogonia will be isolated and their clonogenic potential evaluated by germ cell transplantations. In the second aim, they will determine which signaling pathways are induced by GDNF, leading to Asingle spermatogonia self-renewal or differentiation. In the third aim, they will study how GDNF interacts with other growth factors/receptors to promote self-renewal or differentiation. This work will expand the knowledge of the functional characteristics of the Asingle spermatogonia and lend better insight into the molecular mechanisms that drive the first steps of spermatogenesis. In particular, the role of the growth factor GDNF in regulating self-renewal and/or differentiation will be elucidated. This Career Development Plan will assist Dr. Hofmann in accomplishing her goals. Specifically, it will release her from substantial teaching, thereby allowing her to devote full attention to research, increasing her skills in specific areas of biomedical science and technology. In addition, Dr. Hofmann will not be required to serve on administrative committees, and be released from undergraduate advising duties. At the University of Dayton, the Department of Biology, the College of Arts & Sciences and the Graduate School will provide a supportive environment for the development of Dr. Hofmann's research career. The University of Dayton has recently committed considerable resources to promote interdisciplinary bioscience and engineering research, and Dr. Hofmann is a vital member of our core group of lead investigators. This award will allow her to further collaborations with other departments at our University as well as collaborations with other institutions.