The overarching theme in the Perissi Lab is dissecting the molecular mechanisms that control metabolic adaptation in response to nutrients availability, cell differentiation and oxidative stress. Current projects focus on two main areas:

1) Mechanisms regulating mitochondria-nuclear communication. We have recently identified a novel nuclear- mitochondrial communication pathway based on the translocation of a transcriptional cofactor, called G- Protein Pathway Suppressor 2 (GPS2), from the mitochondria to the nucleus to regulate the expression of nuclear-encoded mitochondrial genes. Our data indicate that GPS2-mediated retrograde signaling is critical for responding to acute mitochondrial stress by depolarization, and for sustaining mitochondrial biogenesis during adipocyte differentiation (Cardamone et al., Molecular Cell, 2018).
2) Dissecting the role of non-proteolytic K63 ubiquitination in the regulation of metabolic reprogramming. This stems from the identification of G-Protein Suppressor 2 (GPS2) as a specific inhibitor of the ubiquitin- conjugating enzyme Ubc13 (Lentucci et al., JBC, 2017). Investigating the role of the GPS2-Ubc13 module within different cellular compartments has led us to describe unexpected roles 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., Molecular Cell, 2012; Cederquist et al., Molecular Metabolism, 2016; Lentucci et al., JBC, 2017). Ongoing studies investigate novel targets of regulation, in addition to addressing the relevance and synergism among these functions in the context of obesity- associated inflammation/insulin resistance and breast cancer.

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