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·霍夫曼博士作为代顿大学生物系的独立研究科学家取得成功。霍夫曼博士的主要兴趣领域是精原干细胞(SSCs)的生物学，即单个精原细胞。单个精原细胞对于了解细胞自我更新和分化的基本机制、治疗生殖功能障碍以及了解睾丸癌，特别是精原细胞瘤的病因具有重要意义。然而，这些细胞的生物学研究受到了严重的阻碍，因为它们的数量很少，没有唯一的标记，而且很难在物理上将它们与其他更成熟的精原细胞分开。霍夫曼博士的团队最近开发了一种方法，可以分离出纯SSCs群体，并开始研究它们的体外行为。利用微阵列，他们还分析了SSCs在胶质细胞系衍生神经营养因子(GDNF)存在的情况下的转录程序，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SSCs更新和分化的信号通路。在第一个目标中，将分离单个精原细胞，并通过生殖细胞移植评估其克隆形成能力。在第二个目标中，他们将确定哪些信号通路是由GDNF诱导的，从而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个精原细胞功能特征的了解，并更好地洞察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实现她的目标。具体地说，这将使她从实质性的教学中解脱出来，从而使她能够完全专注于研究，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行政委员会任职，并从本科生的顾问职责中解脱出来。在代顿大学，生物系、文理学院和研究生院将为霍夫曼博士的研究生涯的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的生物科学和工程研究，霍夫曼博士是我们领导研究人员核心小组的重要成员。这一奖项将使她能够进一步与我们大学的其他系以及与其他机构的合作。

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.