OHSU

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Soren Impey, Ph.D.

Assistant Professor
Admin Unit: SOM-Cell & Developmental Biology Department
Phone: 503-494-7540
Lab Phone: 503-418-5073
Fax: 503-418-5044
Office: BRB Rm 707
Mail Code: L321
Programs:
Cell & Developmental Biology
Neuroscience Graduate Program
Program in Molecular & Cellular Biosciences
Cancer Biology
Research Interests:
Neuroscience Neuronal Differentiation Stem Cell Epigenetics Transcription Chromatin Genomics Embryonic Stem Cell Developmental biology MicroRNA Noncoding RNA » Click here for more about Dr. Impey's research
Preceptor Rotations
Dr. Impey has not indicated availability for preceptor rotations at this time.
Faculty Mentorship
Dr. Impey has not indicated availability as a mentor at this time.
Profile

Soren Impey Ph.D.

Biography

1991-1998 Ph.D., University of Washington
1998-2000 Postdoctoral Fellow, University of Washington
2000-2006 Postdoctoral Fellow, Vollum Institute, OHSU
2006-present Assistant Professor, Oregon Stem Cell Center, Dept. of Cell and Developmental biology, OHSU

Research Interests The Impey lab utilizes functional genomic approaches to characterize the transcriptional and epigenetic networks that regulate stem cell self-renewal and neural differentiation. We recently developed a novel technology, termed Serial Analysis of Chromatin Occupancy (SACO), that enables the identification of transcription factor target sites or epigenetic marks across entire mammalian genomes. The lab also relies on bioinformatics approaches to extract novel biology from our functional genomic and transcriptome screens.

Neurogenesis and neuronal maturation

Our initial SACO screen profiled targets of the transcription factor CREB, an important regulator of neurogenesis, neuronal maturation, and synaptic plasticity. Additional screens revealed a network of ~10,000 high-confidence CREB binding sites in a neural cell line, neuronal progenitors, and cortical neurons. We have recently utilized SACO and transcriptome data to identify hundreds of novel CREB target genes that are potently regulated by neurotrophins and neuronal activity. Remarkably, a significant fraction of inducible CREB-dependent genes are not predicted to code for proteins. Thus, a major focus of the lab is the characterization of these novel non-coding genes and microRNAs. Indeed, our lab was the first to identify a neurotrophin and activity-regulated microRNA that controls neuronal differentiation and synaptogenesis. More recent studies seek to gain additional insight into neurogenesis via screens for developmentally-regulated transcriptional regulators. NIH-supported research

Epigenetic control of embryonic stem cell pluripotency and self-renewal

Embryonic stem (ES) cells isolated from the inner cell mass of murine blostocysts are pluripotent, capable of indefinite symmetric cell division, and can be differentiated into all cellular lineages. The recent isolation of human ES cells holds great promise for the treatment of a variety of degenerative disorders including, but not limited to, Parkinson's disease and diabetes. The homeodomain transcription factors, Oct3/4 and Nanog, are believed to play critical roles in sustaining ES cell pluripotency. Surprisingly, few Oct3/4 or Nanog targets have been linked to pluripotency and it is also not clear how these factors regulate transcription. Initial studies have identified over ~4,000 predicted Nanog target sites in mouse embryonic stem cells. Remarkably, we find that all tested Nanog targets are co-occupied by Oct3/4. More recent studies show that the Oct3/4-Nanog complex recruits a histone-methylation complex associated with active chromatin. We are also characterizing novel Nanog targets that directly regulate the Polycomb and Trithorax epigenetic pathways. These studies suggest that Nanog and Oct3/4 regulate embryonic stem cell self-renewal, at least in part, by controlling epigenetic remodeling. We believe that our studies will reveal epigenetic networks that may facilitate the re-programming of adult cells into pluripotent, ES-like cells. NIH-supported research


 

Selected references:

Impey S*, Fong AL, Wang Y, Cardinaux JR, Fass DM, Obrietan K, Wayman GA, Storm DR, Soderling TR, Goodman R.H. (2002) Phosphorylation of CBP mediates transcriptional activation by neural activity and CaM kinase IV. Neuron. 34,235-244.

Cha-Molstad H, Keller DM, Yochum GS, Impey S., Goodman RH (2004) Cell type-specific binding of the transcription factor CREB to the cAMP-regulated enhancer. Proc. Natl. Acad. Sci. U S A, 101, 13572-13577.

Arthur JS, Fong AL, Dwyer JM, Davare M, Reese E, Obrietan K, Impey S. (2004) MSK1 mediates CREB phosphorylation and activation by neurotrophins. J Neurosci. 24, 4324-32.

Impey S*., McCorckle SR, Cha-Molstad H, Dwyer JM, Yochum GS, Boss JM, McWeeney S, Dunn JJ, Mandel G, Goodman RH (2004) Defining the CREB Regulon: A Genome-Wide Analysis of Transcription Factor Regulatory Regions. Cell. 119, 1041-1054.Highlighted on cover

Vo, N., Klein, M. E., Varlamova, O., Keller, D. M., Yamamoto, T., Goodman, R. H., and Impey, S. (2005). A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. Proc. Natl .Acad Sci U S A 102, 16426-16431.Featured as one of Sciences Signaling Breakthroughs of the Year

Wayman, G.A., Impey, S., Marks, D., Saneyoshi, T., Grant, W.F., Derkach, V.F., and Soderling T.R. (2006) Activity-dependent Dendritic Arborization Mediated by CaM-kinase I Activation and Enhanced CREB-dependent Transcription of Wnt. Neuron 50, 897-909.