Soren Impey, Ph.D.Associate Scientist Peer Reviewed Publications |
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Short Bio:Dr. Impey obtained a PhD in Pharmacology (Program in Neurobiology) at the University of Washington where he generated the first transgenic CREB-reporter mouse that specifically linked CREB activation to memory consolidation and other long-term brain plasticity mechanisms. Dr. Impey joined Richard Goodman’s lab at Oregon Health & Science University (OHSU) as a post-doc in 2000. In the Goodman lab he studied the assembly and regulation of CREB- and CBP-dependent transcriptional complexes in response to neuronal activity. Dr. Impey also worked with the Dunn lab to develop a novel technology that facilitated the unbiased mapping of CREB occupancy across an entire mammalian genome. This technology was published in Cell and was among the first examples of ChIP-Seq. In subsequent work as a faculty member at OHSU, Dr. Impey used functional genomic approaches to identify microRNAs regulated by CREB, neuronal activity, and epilepsy-associated seizures. These approaches led the Impey lab to identify the microRNA 132-212 gene as a rapid response gene that promotes neuronal maturation and synaptogenesis. Hundreds of studies have subsequently implicated this microRNA gene in memory consolidation, brain plasticity, and other adaptive phenotypes. Subsequent work by the Impey lab has focused on characterization of additional non-coding plasticity-regulated genes and the use of epigenetic profiling to identify pathways linked to brain plasticity mechanisms and neurological disease. Dr. Impey joined the Legacy Research Institute in 2020 and continues his studies of the regulation of brain plasticity by transcriptional and epigenetic networks. |
Publication Highlights:
Leptin stimulates synaptogenesis in hippocampal neurons via KLF4 and SOCS3 inhibition of STAT3 signaling.
Post-translational modification localizes MYC to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals.
Bi-directional and shared epigenomic signatures following proton and 56Fe irradiation. Profiling status epilepticus-induced changes in hippocampal RNA expression using high-throughput RNA sequencing. A genome-wide screen of CREB occupancy identifies the RhoA inhibitors Par6C and Rnd3 as regulators of BDNF-induced synaptogenesis. A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. |
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Research Interests:
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Research Focus:The Impey lab utilizes functional genomic approaches to characterize transcriptional and epigenetic networks engaged by experience-dependent and repetitive neuronal activity. A major focus of our lab is to characterize novel CREB-regulated non-coding RNAs and microRNAs and determine whether they contribute to brain plasticity, memory consolidation, and epilepsy using both genomic and genetic approaches. The Impey lab also uses bioinformatic approaches to interrogate, relate, and systematically characterize transcriptional, histone methylation, and DNA methylation networks that are altered by epilepsy in order to shed light on disease mechanisms and to identify potential disease biomarkers. Another major goal of Impey lab is to understand how environmental exposure and brain plasticity modifies DNA methylation and contributes to long-term “reprogramming” of gene expression networks. For these studies we use animal models of epilepsy and radiation-induced cognitive dysfunction to identify DNA methylation signatures that are significantly associated with biologically-relevant transcription with the goal of better understanding how methylation “re-programs” gene expression. In recent publications we have identified specific DNA hydroxymethylation signatures that are highly associated with pathways linked to plasticity mechanisms and are currently exploring the biological significance of these pathways. Our studies have also identified a novel bi-directional epigenetic feature associated with remodeling at transcriptional loci and a specific signature triggered by differing types of radiation exposure that may serve as a stable biomarker of radiation-associated cognitive pathology. In collaboration with the Sorg lab, the Impey lab is studying how the transcription factor, OTX2, regulates perineuronal net formation in cortical models of cognition and biological-clock-associated plasticity. In particular, we are exploring whether OTX2 contributes to fear-based memory consolidation in the prefrontal cortex and whether biological timing pathways reciprocally regulate OTX2-associated plasticity. |
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