Our lab's focus is embryonic stem (ES) and neural stem (NS) cells. We are interested in how a network of transcription factors guides development from the totipotent ES cell to a committed NS cell. We use a model of mammalian neural development in which ES cells efficiently differentiate into neural stem cells in cell culture. This model has 3 advantages: large cell numbers, control over the cellular environment and genetic approaches based on gene targeting. Thus biochemical, genetic and cell biological approaches can be applied to the problem. One project is looking at the role of 3 transcription factor genes ( Olig 1, 2, and 3 ) in specifying neural cell fate; we are studying their transcriptional control and have identified their promoters and candidate regulatory regions. A bioinformatics analysis in collaboration with Barak Cohen reveals in all 3 genes novel, large, highly conserved non-genic sequences with conservation extending from the human to chicken genomes. Another project focuses on “cellular memory” the phenomenon in which stem cells divide continuously but stay locked into a committed state. A third project (in collaboration with Rob Mitra) is exploring PCR colony (polony) technology to profile gene expression of stem cells at the single cell level. The lab maintains collaborations with groups investigating ES cells in neural repair of spinal cord injury and stroke and creates genetically engineered ES cells for these projects.
Research Publications
Lee CS, Tee LY, Dusenbery S, Takata T, Golden JP, Pierchala BA, Gottlieb DI, Johnson EM Jr, Choi DW, Snider BJ (2005 Jan). Neurotrophin and GDNF family ligands promote survival and alter excitotoxic vulnerability of neurons derived from murine embryonic stem cells. Exp Neurol. 191 (1): 65-76. Full Article >
Xian HQ, Werth K, Gottlieb DI (2005 Feb 4). Promoter analysis in ES cell-derived neural cells. Biochem Biophys Res Commun. 327 (1): 155-62. Full Article >
Wei L, Cui L, Snider BJ, Rivkin M, Yu SS, Lee CS, Adams LD, Gottlieb DI, Johnson EM Jr, Yu SP, Choi DW (2005 Jun-Jul). Transplantation of embryonic stem cells overexpressing Bcl-2 promotes functional recovery after transient cerebral ischemia. Neurobiol Dis. 19 (1-2): 183-93. Full Article >
Xian, HQ and Gottlieb, DI “Dividing Olig2-expressing stem cells derived from ES cells” – Glia, (2004) In press Full Article >
Adams LD, Choi L, Xian HQ, Yang A, Sauer B, Wei L, Gottlieb DI (2003 Feb 20). Double lox targeting for neural cell transgenesis. Brain Res Mol Brain Res. 110 (2): 220-33. Full Article >
Masuda T, Mimura S, Takisawa H (2003 Feb). CDK- and Cdc45-dependent priming of the MCM complex on chromatin during S-phase in Xenopus egg extracts: possible activation of MCM helicase by association with Cdc45. Genes Cells. 8 (2): 145-61. Full Article >
Contact Info
David Gottlieb, Ph.D.
Office Location: 964 McDonnell Sciences Bldg.
Office Phone: 314-362-2758
Campus Box: 8108
Fax: 314-362-3446
gottlied@pcg.wustl.edu
