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Bob Thompson

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Primary Appointment: Psychiatry Department
Primary PIBS Dept.: Neuroscience
Department Website

  In the Thompson laboratory, we are interested in the molecular mechanisms that influence and regulate mood/affect, particularly as it is disturbed by stress. Many brain regions are implicated in our normal response to stress yet it remains unclear where, how or why stress (acute or chronic) contributes to mood-related disorders (like depression). To examine these stress-related mechanisms, we utilize a host of molecular/anatomical/genomic approaches and model systems including in vitro culture systems, mouse genetic animal models and human postmortem brain samples.

In the past year or so, our laboratory has explored how stress hormones (e.g. glucocorticoids) influence specific CNS cell types, in particular, astrocytes; a cell type that predominates in the mammalian brain. These studies (by Carter et al) identify key short and long term transcriptional changes that define how these glial cells adapt to glucocorticoids both in vitro as well as in vivo. These steroid-dependent changes have now been extended to chronic stress studies using genetic mouse models that allow us to isolate RNA from astrocytes, dramatically enhancing our ability to better understand how glucocorticoids and stress influence this cell type. We are actively pursuing similar cell-centric approaches to examine how stress influences specific (genetically defined) neuronal cell types are influenced by stress (acute and chronic). Combined, we expect these cell-specific/enriched approaches to allow us to examine the molecular mechanism that are both in common across cell types as well as those unique to a given cell type.

The Thompson lab is also quite interested in the role of small RNAs (e.g. microRNAs) and their involvement in both neuronal development but also in adult CNS functions. We have co-developed a molecular anatomical method to examine microRNAs in developing and adult CNS tissues (Thompson, et al. 2007 Methods 43: 153-161) and are applying this method to the anatomical examination of several microRNAs in the adult CNS. To date, several microRNAs have demonstrated regional as well as cellular patterns of expression that could implicate them in unique or brain-region selective functions. Beyond these neuroanatomical studies, we have developed and analyzed a host of microRNAs profiling methods to determine what microRNAs are expressed in the adult brain (including human) and whether these microRNAs expression patterns vary as a function of disease or treatment. These studies allow us to pose broader research questions such as what microRNAs are expressed in specific brain regions and due these patterns of microRNAs expression change due to disease or treatment? In recent studies in collaboration with the laboratory of Dr. David Turner, we have implemented deep sequencing approaches to examine the expression of microRNAs at an unparalleled level. This methodology has multiple advantages over hybridization-based microRNAs analysis methods including the potential identification of novel microRNAs. Similar to our cell-centric approaches noted above, we remain very interested in how microRNAs are distinguished across cell types and whether mood-related disorders and/or stress influence the expression of microRNAs in a cell-type dependent fashion.