Lab Phone: 617-638-4116
PhD, Molecular Pathology, University of California San Diego
Postdoctoral Training: School of Medicine, University of California San Diego
|M. Dafne Cardamone
The major goal of the Perissi lab is to investigate the transcriptional and non-transcriptional functions of various cofactors with a particular focus on their misregulation during disease states such as cancer, diabetes and other inflammatory disorders. We have been interested for a long time in the regulation of transcriptional events by corepressor and coactivator complexes and in particular we have focused on the NCoR/SMRT corepressors and its associated proteins HDAC3, TBL1 and TBLR1. More recently, based on the finding that another component of the same complex, GPS2, was required for the adipogenic differentiation of 3T3-L1 cells, we began investigating the mechanism of its actions in adipogenesis and uncovered a critical, non-transcriptional role for GPS2 in regulating the enzymatic activity of the TRAF2/CIAP1/Ubc13 ubiquitin conjugating complex and therefore inhibiting the pro-inflammatory TNFalpha pathway. Our goal now is to investigate, both in vitro and in vivo, in tissue-specific mouse models, how the different components of the NCoR complex contribute to broadly regulate the cellular responses to external stimulation by acting in different cellular compartments to modulate hormonal and inflammatory pathways. Ongoing projects aim at: i) determining GPS2 role in the regulation of K63 ubiquitin chain formation within inflammatory responses regulated by Toll-like receptors and TNFalpha in macrophages and B-cells; ii) dissecting the molecular mechanism of GPS2 role in nuclear receptor-mediated transcriptional regulation in differentiating and mature adipocytes; iii) understanding how GPS2 sub-cellular localization and specific functions are regulated by post-translational modifications in different cell types.
Please contact Dr. Perissi by e-mail for more information about open positions for postdoctoral fellows and graduate students.
- The Co-Repressor SMRT Delays DNA Damage-Induced Caspase Activation by Repressing Pro-Apoptotic Genes and Modulating the Dynamics of Checkpoint Kinase 2 Activation. Scafoglio C, Smolka M, Zhou H, Perissi V, Rosenfeld MG. PLoS One. 2013 May 17;8(5):e59986.
- Cardamone M.D., Krones A., Tanasa B., Taylor H., Ricci L., Ohgi K.A., Glass C.K., Rosenfeld M.G. & Perissi V. A protective strategy against hyperinflammatory responses requiring the non-transcriptional actions of GPS2. Molecular Cell 2012 Apr 13;46(1):91-104.
- Perissi V., Jepsen K., Glass C.K. and Rosenfeld M.G. Deconstructing repression: evolving models of corepressors actions. Nature Reviews Genetics, 11(2): 109-23, 2010.
- Perissi V., Scafoglio C., Zhang J., Ohgi K.A., Rose D.W., Glass C.K. & Rosenfeld M.G. Phosphorylation of TBL1 and TBLR1 on Promoters of Regulated Genes Overcomes a Dual Transcriptional Repression Checkpoint Imposed by CtBP and NCoR/SMRT. Molecular Cell, 29 (6), 755-66, 2008.
- Perissi V., Aggarwal A., Glass C.K., Rose D.W. & Rosenfeld M.G. A corepressor/coactivator exchange complex required for transcriptional activation by nuclear receptors, and other regulated transcription factors. Cell, 116(4): 511-26, 2004.
- Perissi V., Staszewski L.M., McInerney E.M., Kurokawa R., Krones A., Rose D.W., Lambert M.H., Milburn M.V., Glass C.K. & Rosenfeld M.G. Molecular determinants of nuclear receptor-corepressor interaction. Genes&Development, 13 (24), 3198-3208, 1999.
- Perissi V., Dasen J.S., Kurokawa R., Wang Z., Korzus E., Rose D.W., Glass C.K. & Rosenfeld M.G. Factor specific modulation of CREB-binding protein acetyltransferase activity. PNAS, 96(7), 3652-3657