{"id":67,"date":"2014-03-26T17:32:45","date_gmt":"2014-03-26T21:32:45","guid":{"rendered":"http:\/\/blogs.bu.edu\/vperissi\/?page_id=67"},"modified":"2023-09-28T21:58:43","modified_gmt":"2023-09-29T01:58:43","slug":"research","status":"publish","type":"page","link":"https:\/\/sites.bu.edu\/perissilab\/research\/","title":{"rendered":""},"content":{"rendered":"<p>The overarching theme in the Perissi Lab is <strong>dissecting the molecular mechanisms that control adaptive responses to metabolic stress and pro-inflammatory signals in adipocytes and immune cells<\/strong>.<\/p>\n<p>A major\u00a0area of interest is <span><strong>nuclear-mitochondrial communication<\/strong>.\u00a0W<\/span>e\u00a0recently identified G-Protein Suppressor 2 (GPS2) as a mediator of mitochondrial retrograde signaling and a required transcriptional cofactor for the expression of nuclear-encoded mitochondrial genes. Our data indicate that GPS2\u00a0regulated\u00a0<span>translocation from the mitochondria to the nucleus <\/span> is critical for responding to acute mitochondrial stress and for sustaining mitochondrial biogenesis during adipocyte differentiation (Cardamone et al., <i>Mol Cell,\u00a0<\/i>2018).<\/p>\n<p>We also focus is on <strong>non-proteolytic K63 ubiquitination<\/strong> as a key regulatory event for cellular adaptation. This stems from the identification of GPS2 as a specific inhibitor of the ubiquitin-conjugating enzyme Ubc13 (Lentucci et al., <em>JBC<\/em>, 2017). Investigating the role of the GPS2-Ubc13 module within different cellular compartments led us to describe an unexpected role for GPS2 as a suppressor of PI3K\/AKT signaling downstream of the insulin receptor and as an inhibitor of TLR and TNFR pro-inflammatory signaling pathways (Cardamone et al., <em>Molecular Cell<\/em>, 2012; Cederquist et al., <em>Molecular Metabolism<\/em>, 2016; Lentucci et al., <em>JBC<\/em>, 2017). GPS2-mediated inhibition of Ubc13 activity is also important for chromatin remodeling and priming of target gene promoters in the nucleus (Cardamone et al., <em>Cell Reports<\/em>, 2014; Cardamone et al., <i>Mol Cell,\u00a0<\/i>2018).<\/p>\n<p>Ongoing studies investigate the relevance and synergism among these functions in the context of obesity-associated inflammation\/insulin resistance and breast cancer. \u00a0Techniques routinely employed in the lab include basic molecular biology <span>and biochemical approaches <\/span>(site-specific mutagenesis, CRISPR editing, gene expression analyses, protein-protein interaction studies, in vitro enzymatic\u00a0assays), next generation sequencing (ChIPseq, RNAseq, GROseq) and <em>in vivo <\/em>studies (mouse models of tissue-specific GPS2 knock-out).<\/p>\n<p>&nbsp;<\/p>\n<p><img loading=\"lazy\" src=\"\/perissilab\/files\/2014\/03\/Webpage-Research-Summary-2018-636x472.png\" alt=\"\" width=\"636\" height=\"472\" class=\"wp-image-413 size-medium aligncenter\" srcset=\"https:\/\/sites.bu.edu\/perissilab\/files\/2014\/03\/Webpage-Research-Summary-2018-636x472.png 636w, https:\/\/sites.bu.edu\/perissilab\/files\/2014\/03\/Webpage-Research-Summary-2018-768x570.png 768w, https:\/\/sites.bu.edu\/perissilab\/files\/2014\/03\/Webpage-Research-Summary-2018-1024x760.png 1024w, https:\/\/sites.bu.edu\/perissilab\/files\/2014\/03\/Webpage-Research-Summary-2018.png 1630w\" sizes=\"(max-width: 636px) 100vw, 636px\" \/><\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The overarching theme in the Perissi Lab is dissecting the molecular mechanisms that control adaptive responses to metabolic stress and pro-inflammatory signals in adipocytes and immune cells. A major\u00a0area of interest is nuclear-mitochondrial communication.\u00a0We\u00a0recently identified G-Protein Suppressor 2 (GPS2) as a mediator of mitochondrial retrograde signaling and a required transcriptional cofactor for the expression of [&hellip;]<\/p>\n","protected":false},"author":16087,"featured_media":0,"parent":0,"menu_order":5,"comment_status":"open","ping_status":"open","template":"page-templates\/no-sidebars.php","meta":[],"_links":{"self":[{"href":"https:\/\/sites.bu.edu\/perissilab\/wp-json\/wp\/v2\/pages\/67"}],"collection":[{"href":"https:\/\/sites.bu.edu\/perissilab\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/sites.bu.edu\/perissilab\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/sites.bu.edu\/perissilab\/wp-json\/wp\/v2\/users\/16087"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.bu.edu\/perissilab\/wp-json\/wp\/v2\/comments?post=67"}],"version-history":[{"count":8,"href":"https:\/\/sites.bu.edu\/perissilab\/wp-json\/wp\/v2\/pages\/67\/revisions"}],"predecessor-version":[{"id":819,"href":"https:\/\/sites.bu.edu\/perissilab\/wp-json\/wp\/v2\/pages\/67\/revisions\/819"}],"wp:attachment":[{"href":"https:\/\/sites.bu.edu\/perissilab\/wp-json\/wp\/v2\/media?parent=67"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}