Shaad米. 艾哈迈德

助理教授

Ph.D.斯坦福大学医学院教授

电话: 812-237-2390

电子邮件: Shaad.艾哈迈德@azarnewsonline.com

办公室: 科学楼287H

艾哈迈德实验室网站: http://facultyhandbook.azarnewsonline.com/cas/AhmadLab

主要研究方向: Cardiogenesis (心发展); Organogenesis; Transcriptional regulatory networks; Systems biology; 发展al biology; Computational biology; Genetics; Functional 基因组s

A comparison of the molecular mechanisms governing 心发展 in vertebrates and 果蝇 reveals a remarkable conservation of all major regulatory components, 包括信号因子和转录因子. 此外, many of these conserved cardiac regulators are found to be mutated in various types of human congenital heart disease. 心脏发育相关基因的鉴定 果蝇 and detailed investigations of their functions thus provide considerable insight into related mechanisms controlling cardiogenesis in vertebrates, 包括人类.

我的实验室采用综合遗传技术, 基因组, computational strategies to identify novel genes involved in 果蝇 心发展, 研究它们的功能和调节, examine the role of their orthologs in vertebrate and mammalian cardiogenesis. Our ultimate goal is to arrive at a comprehensive understanding of 心发展 which incorporates both a systems-level view of the underlying genetic network and detailed examinations of the roles of individual genes.

We also use similar integrated approaches to examine and dissect biological processes involved in the development of other organs besides the heart. 实验室目前的研究项目包括:

Functional analysis of cardiogenic processes regulated by Forkhead (Fkh/Fox) transcription factors.

At least 4 transcription factors (TFs) of the Forkhead (Fkh/Fox) family are required for proper cardiac development in mammals, while mutations in 3 Fkh genes have been linked to human congenital heart defects. 然而, relatively little is known about the molecular mechanisms or the downstream targets by which these Fkh-mediated developmental functions are brought about. 我们之前在 果蝇 确定了两个Fkh基因的作用， 朱木和ches -1, in specifying cardiac cell subtypes and number by mediating cardiac progenitor cell divisions, 并决定心脏的命运. We also showed that Fkh TF binding sites were significantly enriched in the enhancers of cardiac genes. 集体, these results indicate that these two Fkh TFs integrate multiple cardiogenic processes by regulating a large number of downstream target genes, raising the question of what these target genes are and what their individual functions might be during 心发展.

Utilizing genome-wide transcription expression profiles of mesodermal cells from wild-type embryos and embryos with appropriate genetic perturbations in the Fkh genes, 我们已经确认了963 时候-管制和427 CHES-1-like -调控靶基因. We are now identifying and functionally analyzing the diverse cardiogenic cellular processes mediated by these Fkh targets.

Determining the functional roles of regulatory genes implicated in cardiogenesis.

通过结合表达分析, statistical meta-analysis and large scale in situ hybridizations, 我们已经确定了新颖 果蝇 regulatory genes expressed in the heart or its precursor, the cardiac mesoderm. 在一个单独的项目中, using machine learning to classify cardiac enhancers based primarily on the transcription factor binding sites of orthologous vertebrate TFs, 我们还确定了 果蝇 TFs调节心脏基因. An ongoing screen based on knockdown RNA interference assays and loss-of-function mutant analysis has already determined that 48 of these genes exhibit robust cardiac phenotypes when their functions are disrupted. We are now examining the functional roles of these 48 regulatory genes in 心发展 in greater detail.

间质-上皮转化(METs)的检查.

从松散关联的过渡, polarity-lacking mesenchymal cells to planar arrays of tightly-packed epithelial cells characterized by apical-basal polarity plays a critical role not only in mammalian cardiogenesis, but also in hepatogenesis (liver development) and nephrogenesis (kidney development). 我们正在用a学习MET 果蝇 imaginal disc model which exhibits a remarkable conservation of signals with mammalian kidney development.

选定的出版物

附近潘塔,M.坎普，A. J.施瓦布，K. R., 艾哈迈德,年代. M. (2022). Assessing the Roles of Potential Notch Signaling Components in Instructive and Permissive Pathways with Two 果蝇 Pericardial Reporters. 分子生物学方法 2472, 109-130. 下载 (750 KB)

坎普,. J.潘塔，M.施瓦布，K. R.Inlow, M. H., 艾哈迈德,年代. M. (2021). The 果蝇 Forkhead/Fox transcription factor Jumeau mediates specific cardiac progenitor cell divisions by regulating expression of the kinesin Nebbish. 科学报告 11, 3221.下载 - (3.30 MB)

附近潘塔,M.坎普，A. J.达拉斯，J. M.施瓦布，K. R., 艾哈迈德,年代. M. (2020). 三种不同的机制, 切口有益的, 宽容的, 和独立, regulate the expression of two different pericardial genes to specify cardiac cell subtypes. 《澳门合法赌场官网》 15, e0241191. 下载 - (3.32 MB)

艾哈迈德,年代. M. (2017). 果蝇心脏发育中的保守信号机制. 发展动态 246, 641-656. 下载 - (748 KB)

艾哈迈德,年代. M.巴塔查里亚，P.纽约州杰弗里斯(Jeffries.吉塞尔布雷希特，S. S. 迈克尔逊，A. M. (2016). Two Forkhead transcription factors regulate cardiac progenitor specification by controlling the expression of receptors of the fibroblast growth factor and Wnt signaling pathways. 发展 143, 306-317. 下载 - (2.96 MB)

艾哈迈德,年代. M.B. W.黄，博士.Cozart, E. J.米肖，S.朱，X.纽约州杰弗里斯(Jeffries.阿布哈利勒(Aboukhalil.Bulyk, M.L.奥夫查连科，我. 迈克尔逊，A. M. (2014).  Machine learning classification of cell-specific cardiac enhancers uncovers developmental subnetworks regulating progenitor cell division and cell fate specification.  发展 141, 878-888. 下载- (5.55 MB)

艾哈迈德,年代. M.坦西，T. R.B. W.诺尔特，M. T.纽约州杰弗里斯(Jeffries.吉塞尔布雷希特，S. S.纽约州，鲁桑市. M. 迈克尔逊，A. M. (2012).  Two Forkhead transcription factors regulate the division of cardiac progenitor cells by a Polo-dependent pathway.  细胞发育 23, 97-111. 下载- (1.13 MB)

朱,X., 艾哈迈德,年代. M.阿布哈利勒(Aboukhalil.B. W.Kim, Y.坦西，T. R.海莫维奇，A.纽约州杰弗里斯(Jeffries.Bulyk, M. L. 迈克尔逊，A. M. (2012).  Differential regulation of mesodermal gene expression by 果蝇 cell type-specific Forkhead transcription factors.  发展 139, 1457-1466. 下载- (1.07 MB)

艾哈迈德,年代. M. 贝克，B. S. (2002).  Sex-specific deployment of FGF signaling in 果蝇 recruits mesodermal cells into the male genital imaginal disc.  细胞 109, 651-661. 下载 - (448 KB)

科学要闻 《澳门合法赌场官网》:Burtis, K. C. (2002).  中间是双性的.  科学 297, 1135-1136. 下载- (260 KB)

克里斯琴森,. E.Keisman, E. L., 艾哈迈德,年代. M. 贝克，B. S. (2002).  性来自寒冷.  遗传学趋势 18, 510-516. 下载 - (189 KB)