Responses to cellular stress, differentiation processes, metabolic changes, hormonal stimulations… all associate with broad changes in gene expression. In the Perissi lab, we investigate how different inputs are integrated and translated in fine-tuning of transcriptional regulation via the action of signal transduction pathways, ubiquitin conjugating machineries and chromatin remodeling enzymes. Our current focus is on understanding how different components of the NCoR/SMRT corepressor complex contribute to broadly regulate the cellular responses to external stimuli and changes in bioenergetics needs through transcriptional and non-transcriptional functions. To dissect these functions, we take a multidisciplinary approach that includes in vitro biochemical and cellular experiments, in vivo modeling using tissue-specific mouse models, and high throughput next generation sequencing approaches. By understanding how cells modulate hormonal, metabolic and inflammatory gene programs in physiological conditions, we hope to contribute to clarify what happens when the same pathways are disrupted under pathological conditions.
Dafne Cardamone – Research Assistant Professor
Stefanie Chan – Graduate Student
Justin English – Graduate Student
Yuan Gao – Postdoctoral Fellow
Joey Orofino – Graduate Student
Aaron Shambley – MA student
Emma Smith – Research Assistant
Megan Sheeran – Undergraduate
Kevin Kuang – Undergraduate Student
Cardamone MD, Tanasa B, Cederquist CT, Huang J, Mahdaviani K, Li W, Rosenfeld MG, Liesa M, Perissi V. Mitochondrial Retrograde Signaling in Mammals Is Mediated by the Transcriptional Cofactor GPS2 via Direct Mitochondria-to-Nucleus Translocation. Mol Cell. 2018 Mar 01; 69(5):757-772.e7. PMID: 29499132.
Mahdaviani K, Benador IY, Su S, Gharakhanian RA, Stiles L, Trudeau KM, Cardamone M, Enríquez-Zarralanga V, Ritou E, Aprahamian T, Oliveira MF, Corkey BE, Perissi V, Liesa M, Shirihai OS. Mfn2 deletion in brown adipose tissue protects from insulin resistance and impairs thermogenesis. EMBO Rep. 2017 Jul; 18(7):1123-1138. PMID: 28539390.
Cederquist CT, Lentucci C, Martinez-Calejman C, Hayashi V, Orofino J, Guertin D, Fried SK, Lee MJ, Cardamone MD, Perissi V. Systemic insulin sensitivity is regulated by GPS2 inhibition of AKT ubiquitination and activation in adipose tissue. Molecular Metabolism. 2016; 1(6):125-137.
Lentucci C, Belkina A, Cederquist CT, Chan M, Johnson HE, Prasad S, Lopacinski A, Nikolajczyk BS, Monti S, Snyder-Cappione J, Tanasa B, Cardamone MD, Perissi V. Inhibition of Ubc13-mediated ubiquitination by GPS2 regulates multiple stages of B cell development. J Biol Chem. 2016 Dec 30. PMID: 28039360.
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Huang J, Cardamone MD, Johnson HE, Neault M, Chan M, Floyd ZE, Mallette FA, Perissi V. Exchange Factor TBL1 and Arginine Methyltransferase PRMT6 Cooperate in Protecting G Protein Pathway Suppressor 2 (GPS2) from Proteasomal Degradation. J Biol Chem. 2015 Jul 31; 290(31):19044-54. PMID: 26070566.
Cardamone MD, Tanasa B, Chan M, Cederquist CT, Andricovich J, Rosenfeld MG, Perissi V. GPS2/KDM4A pioneering activity regulates promoter-specific recruitment of PPAR?. Cell Rep. 2014 Jul 10; 8(1):163-76. PMID: 24953653.
Scafoglio C, Smolka M, Zhou H, Perissi V, Rosenfeld MG. The co-repressor SMRT delays DNA damage-induced caspase activation by repressing pro-apoptotic genes and modulating the dynamics of checkpoint kinase 2 activation. PLoS One. 2013; 8(5):e59986. PMID: 23690919.
Cardamone MD, Krones A, Tanasa B, Taylor H, Ricci L, Ohgi KA, Glass CK, Rosenfeld MG, Perissi V. A protective strategy against hyperinflammatory responses requiring the nontranscriptional actions of GPS2. Mol Cell. 2012 Apr 13; 46(1):91-104. PMID: 22424771.
Perissi V, Jepsen K, Glass CK, Rosenfeld MG. Deconstructing repression: evolving models of co-repressor action. Nat Rev Genet. 2010 Feb; 11(2):109-23. PMID: 20084085.
Huang W, Ghisletti S, Perissi V, Rosenfeld MG, Glass CK. Transcriptional integration of TLR2 and TLR4 signaling at the NCoR derepression checkpoint. Mol Cell. 2009 Jul 10; 35(1):48-57. PMID: 19595715.
Perissi V, Scafoglio C, Zhang J, Ohgi KA, Rose DW, Glass CK, Rosenfeld MG. TBL1 and TBLR1 phosphorylation on regulated gene promoters overcomes dual CtBP and NCoR/SMRT transcriptional repression checkpoints. Mol Cell. 2008 Mar 28; 29(6):755-66. PMID: 18374649.
Complete list can be found at BU Profiles