MOLECULAR BIOLOGY OF UTERINE FUNCTION DURING PREGNANCY

Edward K.S.Chien，M.D.获得化学学士学位 1984年获得工程学学位，1988年从加州大学获得医学学位 伊利诺伊州。在他担任妇产科住院医师后， 他完成了密歇根大学医学中心的临床研究 在马克·菲利普医学博士的指导下， 在芝加哥大学。在他担任临床研究员期间，他在 在马克·菲利普博士的实验室里，研究了信号 子宫肌层细胞的转导机制。 两年前，钱博士申请并获得了一名生殖科学家 发展计划奖。在那段时间里，他发现 子宫肌层中妊娠调控基因的差异表达 信使RNA在Graeme I.Bell博士的指导下显示。 从这些初步研究中，钱博士制定了一份广泛的清单 似乎受妊娠调控的候选基因。这个 本申请的发起人格雷姆·贝尔博士是一名国际 关于单基因和多基因形式的糖尿病和 确定了许多与成熟度相关的转录因子 年轻人的糖尿病发作。他与钱博士在 本项目的方方面面。 这项提案的广泛、长期目标是确定和 确认子宫肌层特异的、妊娠调节的基因 了解围绕其监管的机制。更多 具体地说，子宫肌层在怀孕期间经历了显著的变化。 基因表达发生了显著变化。分子机制 这些变化背后的原因是有待确定的。的监管要素 子宫肌层特异性基因在不同发育阶段的差异表达 怀孕的身份将被确定。这些元素的计算结果将为 确定它们在与怀孕相关的变化中的作用。理解 调节子宫肌层功能变化的机制将允许 治疗早产和产后的新疗法的发展 怀孕。 用于识别妊娠调控基因的方法包括 差异表达、基因芯片杂交和蛋白质组 分析。基因组序列将通过噬菌体文库获得 用Northern软件确认组织特异性调控后的筛选 斑点杂交和半定量逆转录聚合酶链法 反应。通过细胞转染法识别调节区 用报告基因构建的实验。

Edward K.S. Chien, M.D., received a baccalaureate degree in chemical engineering in 1984 and a medical degree in 1988 from the University of Illinois. Following his residency in Obstetrics and Gynecology at the University of Michigan Medical Center he completed a clinical fellowship in Maternal Fetal Medicine under the direction of Mark Phillippe, M.D., at the University of Chicago. During his clinical fellowship he worked in the laboratory of Dr. Mark Phillippe and investigated signal transduction mechanisms of myometrial cells. Two years ago Dr. Chien applied and received a Reproductive Scientist Development Program award. During that period of time he identified gestational regulated genes in the myometrium using differential messenger RNA display under the guidance of Dr. Graeme I. Bell, PhD. From these preliminary studies Dr. Chien has developed an extensive list of candidate genes which appear to be gestationally-regulated. The sponsor in the present application, Dr. Graeme Bell, is an international authority on monogenic and polygenic forms of diabetes mellitus and identified a number of transcription factors associated with maturity onset diabetes of the young. He has worked closely with Dr. Chien on all aspects of the present project. The broad, long-term objectives of this proposal is to identify and confirm, myometrial specific, gestationally-regulated genes and to understand the mechanisms surrounding their regulation. More specifically, the myometrium undergoes marked changes during pregnancy with significant changes in gene expression. The molecular mechanism behind these changes are to be identified. The regulatory elements of myometrial specific genes undergoing differential expression during pregnancy will be identified. These elements will be evaluated to determine their role in the changes related to pregnancy. Understanding the mechanism regulating changes in myometrial function will permit the development of novel therapies to treat preterm labor and post term pregnancies. The methods used to identify gestationally-regulated genes include differential mRNA display, cDNA array hybridization, and proteome analysis. Genomic sequences will be obtained by bacteriophage library screening after confirming tissue specific regulation with Northern blots and semi-quantitative reverse transcription-polymerase chain reaction. Regulatory regions are identified by cell transfection experiments with reporter gene constructs.