The main scientific interest of the Leukocyte biology Unit is the dissection of how adhesive interactions control the onset and maintenance of complex biological responses in multicellular organisms, and how dysregulation of such responses contributes to the pathogenesis of major diseases, such as cancer and chronic inflammatory diseases. The group focuses on the role of adhesion receptors in cell proliferation, survival and migration.
To this aim the unit established a fundamental role of G protein-coupled receptor associated beta-arrestins as scaffolds catalyzing the assembly of molecular complexes that control the spatial and temporal regulation of integrin function. Downstream of chemokine stimulation, tissue- infiltrating myeloid cells display activation of the Stress Activated Protein Kinase (SAPK) pathway.
The Leukocyte biology Unit is currently investigating the pro-inflammatory function of the Stress Activated Protein Kinase pathway by assessing the transcriptome, proteome and secretome of primary myeloid cells inducibly activating the upstream SAPK member MLK3. Secreted matricellular proteins seem to be a crucial intermediate in the genetic programs of activation and differentiation spurred by SAPK activity in myeloid cells.
Molteni R, Bianchi E, Patete P, Fabbri M, Baroni G, Dubini G, Pardi R. A novel device to concurrently assess leukocyte extravasation and interstitial migration within a defined 3D environment. Lab Chip. 2015 Jan 7;15(1):195-207.
Panattoni M, Maiorino L, Lukacs A, Zentilin L, Mazza D, Sanvito F, Sitia G, Guidotti LG, Pardi R. The COP9 signalosome is a repressor of replicative stress responses and polyploidization in the regenerating liver. Hepatology 2014;59:2331-2343.
Porrello E, Rivellini C, Dina G, Triolo D, Del Carro U, Ungaro D, Panattoni M, Feltri ML, Wrabetz L, Pardi R, Quattrini A, Previtali SC. Jab1 regulates Schwann cell proliferation and axonal sorting through p27. J Exp Med. 2014;211(1):29-43.
Morrison AR, Yarovinsky TO, Young BD, Moraes F, Ross T, Ceneri N, Zhang J, Zhuang ZW, Sinusas AJ, Schwartz MA, Simons M, Pardi R, Bender JR. Chemokine-couple b2 integrin-induced Rac2-Myosin IIA interaction regulates VEGF-A mRNA stability and arteriogenesis. J Exp Med. 2014; 211:1957-1968.
Lage Crespo C, Vernieri C, Bender JR, Wittbrodt J, Pardi R. The PAR complex directs spatial coordination and dynamics of the F-actin and microtubule networks to control vectorial leukocyte migration in vivo. J. Cell Sci. 2014;127:4381-4395.
Deng Z, Wei N, Miller D, Mountz JD, Pardi R, Huang-Ge Z. Plant Homologue Constitutive photomorphogenesis 9 (COP9) signalosome regulates innate immune responses in experimental sepsis. Blood 2011;117:4796-4804.
Molteni R, Lage-Crespo C, Feigelson S, Moser C, Fabbri M, Krombach F, Alon R and Pardi R. β-arrestins are required for the induction and strengthening of shear-stress resistant adhesion during leukocyte extravasation. Blood 2009;114:1073-1082.
Panattoni M, Sanvito F, Basso V, Doglioni C, Montini E, Bender Jr, Mondino A, Pardi R. Targeted inactivation of the Cop9 signalosome impairs multiple stages of T cell development. Journal of Experimental Medicine 2008; 205:465-477.
Savio MG, Rotondo G, Maglie S, Rossetti G, Bender JR, Pardi R. Cop1D, an alternatively spliced Constitutive Photomorphogenetic-1 (COP1) product, stabilizes UV stress-induced C-Jun through inhibition of full length COP1. Oncogene 2008;27: 2401-2411.
Bianchi E, Denti S, Granata A, Geginat J, Rogge L and Pardi R. The integrin LFA-1 interacts with the transcriptional coactivator JAB1 to modulate AP-1 transcriprional activity. Nature 2000;404: 617-621.