Malignant B cells Biology and 3D modelling
The aim of Scielzo's research projects is to study the interactions occurring between leukemic cells and their microenvironment by focusing on the role of the cytoskeleton. Though the precise mechanisms are currently unknown, it is likely that the interactions between leukemic cells and the microenvironment are extremely dynamic and depend on the continuous re-circulation and homing into the lymphoid tissues where leukemic cells origin, grow and acquire pharmacological resistance. In particular, cell movement, attachment and interactive structure formations involve complex molecular mechanisms and mechanical forces, brought about by cytoskeletal reorganization into specialized microenvironments.
Understanding those mechanisms and the responsible genes that account for the molecular and cellular interactions occurring among leukemic cells and the microenvironment is expected to lead to new therapeutic strategies.
The group demonstrated that the expression, activation and function of cytoskeletal proteins (HS1) and Kinases (LYN) conceivably play a crucial role in CLL, acting as hub molecules between the B cell receptor and the cytoskeleton. Taking advantage of primary leukemic cells and cell lines the group is developing new 3D co-culture models by prototyping a bench-top 3D bio-printer and dynamic growth in bioreactors combined them with real-time imaging strategies.
McMahon KM, Scielzo C, Angeloni NL, Deiss-Yehiely E, Scarfo L, Ranghetti P, Ma S, Kaplan J, Barbaglio F, Gordon LI, Giles FJ, Thaxton CS, Ghia P. Synthetic high-density lipoproteins as targeted monotherapy for chronic lymphocytic leukemia. Oncotarget. Feb 14;8(7):11219-11227, 2017
Galletti G, Scielzo C, Barbaglio F, Rodriguez TV, Riba M, Lazarevic D, Cittaro D, Simonetti G, Ranghetti P, Scarfò L, Ponzoni M, Rocchi M, Corti A, Anselmo A, van Rooijen N, Klein C, Ries CH, Ghia P, De Palma M, Caligaris-Cappio F, Bertilaccio MT. Targeting Macrophages Sensitizes Chronic Lymphocytic Leukemia to Apoptosis and Inhibits Disease Progression. Cell Rep. Feb 10; 2016
Agathangelidis A, Scarfò L, Barbaglio F, Apollonio B, Bertilaccio MT, Ranghetti P, Ponzoni M, Leone G, De Pascali V, Pecciarini L, Ghia P, Caligaris-Cappio F, Scielzo C Establishment and Characterization of PCL12, a Novel CD5+ Chronic Lymphocytic Leukaemia Cell Line. PLoS One. Jun 25;10(6):e0130195, 2015
Apollonio B, Bertilaccio MT, Restuccia U, Ranghetti P, Barbaglio F, Ghia P, Caligaris-Cappio F, Scielzo C. From a 2DE-gel spot to protein function: lesson learned from HS1 in chronic lymphocytic leukemia. J Vis Exp. Oct 19;(92):e51942; 2014
Caligaris-Cappio F, Bertilaccio MT, Scielzo C. How the microenvironment wires the natural history of chronic lymphocytic leukemia. Semin Cancer Biol. Feb;24:43-8; 2014
Hacken E, Scielzo C, Bertilaccio MT, Scarfò L, Apollonio B, Barbaglio F, Stamatopoulos K, Ponzoni M, Ghia P, Caligaris-Cappio F. Targeting the LYN/HS1 signaling axis in chronic lymphocytic leukemia. Blood. Mar 21;121(12):2264-73; 2013
Scielzo C, Apollonio B, Scarfò L, Janus A, Muzio M, Ten Hacken E, Ghia P, Caligaris-Cappio F. The functional in vitro response to CD40 ligation reflects a different clinical outcome in patients with chronic lymphocytic leukemia. Leukemia. Nov;25(11):1760-7; 2011
Scielzo C, Bertilaccio MT, Simonetti G, Dagklis A, ten Hacken E, Fazi C, Muzio M, Caiolfa V, Kitamura D, Restuccia U, Bachi A, Rocchi M, Ponzoni M, Ghia P, Caligaris-Cappio F. HS1 has a central role in the trafficking and homing of leukemic B cells. Blood. Nov 4;116(18):3537-46; 2010
Muzio M, Scielzo C, Frenquelli M, Bachi A, De Palma M, Alessio M, Ghia P, Caligaris-Cappio F. HS1 complexes with cytoskeleton adapters in normal and malignant chronic lymphocytic leukemia B cells. Leukemia. 2007 Sep;21(9):2067-70;
Scielzo C, Ghia P, Conti A, Bachi A, Guida G, Geuna M, Alessio M, Caligaris-Cappio F. HS1 protein is differentially expressed in chronic lymphocytic leukemia patient subsets with good or poor prognoses. J Clin Invest. 2005 Jun;115(6):1644-5;