The tumor cell cytoskeleton activity and the cross-talk with the microenvironment have a central role in cancer. 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 and grow.
Chronic Lymphocytic Leukemia (CLL), the adult most frequent B-cell malignancy and still an incurable blood cancer, is a pragmatic example.
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
In particular we aim at elucidating, the expression, activation and functions of hemopoietic-cell-lineage specific 1 (HS1) protein by developing new 3D co-culture models.
Cristina received her doctor degree in Medical Biotechnology at Università Vita- Salute San Raffaele, in the Lab of Prof Caligaris-Cappio and Prof Paolo Ghia. In 2012 she obtained a PhD in Physiology at University of Milano. During these years she focused her research interests on the interplay between leukemic cells and the microenvironment, making important contributions to the field. In 2005, she implemented biochemical studies to the molecular characterization of chronic lymphocytic leukemia (CLL) cells, which led to the identification of HS1 protein as a new prognostic factor. This opened a new line of research focused on the properties of the leukemic cells cytoskeleton and its role in regulating cells interactions with the microenvironment. Thanks to her experience as Visiting Scientist at CNIC in Madrid (Spain), she acquired new skills to optimize imaging techniques.
Since 2016, she is Project Leader at IRCCS Ospedale San Raffaele at the division of Experimental Oncology. Her team is studying the tumour cell/microenvironment interactions in CLL by unravelling HS1 protein mediated cytoskeletal activities. In parallel, they are developing new 3D in vitro co-culture systems by prototyping a bench-top 3D bio-printer.
Her research activity is supported by AIRC (Associazione Italiana per la ricerca sul cancro) and ROCHE per la ricerca. Cristina has published >36 articles in peer-reviewed journals. Her work has been cited > 2375 times, with an H-index of 25 and IF > 340.
The aim of the group headed by Cristina Scielzo 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, 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.
In the past she 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.
Federica Barbaglio Research technician
Luca Pavesi PhD student
- Synthetic high-density lipoproteins as targeted monotherapy for chronic lymphocytic leukemia. Oncotarget. 2017 Feb 14;8(7):11219-11227, 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. *authors equally contributed
- Targeting Macrophages Sensitizes Chronic Lymphocytic Leukemia to Apoptosis and Inhibits Disease Progression. Cell Rep. 2016 Feb 10; 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.
- Establishment and Characterization of PCL12, a Novel CD5+ Chronic Lymphocytic Leukaemia Cell Line. PLoS One. 2015 Jun 25;10(6):e0130195; 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*, * corresponding author
- From a 2DE-gel spot to protein function: lesson learned from HS1 in chronic lymphocytic leukemia. J Vis Exp. 2014 Oct 19;(92):e51942; Apollonio B, Bertilaccio MT, Restuccia U, Ranghetti P, Barbaglio F, Ghia P, Caligaris-Cappio F, Scielzo C.
- How the microenvironment wires the natural history of chronic lymphocytic leukemia. Semin Cancer Biol. 2014 Feb;24:43-8; Caligaris-Cappio F, Bertilaccio MT, Scielzo C.
- Targeting the LYN/HS1 signaling axis in chronic lymphocytic leukemia. Blood. 2013 Mar 21;121(12):2264-73; Hacken E*, Scielzo C*, Bertilaccio MT, Scarfò L, Apollonio B, Barbaglio F, Stamatopoulos K, Ponzoni M, Ghia P, Caligaris-Cappio F. * corresponding author
- The functional in vitro response to CD40 ligation reflects a different clinical outcome in patients with chronic lymphocytic leukemia. Leukemia. 2011 Nov;25(11):1760-7; Scielzo C, Apollonio B, Scarfò L, Janus A, Muzio M, Ten Hacken E, Ghia P, Caligaris-Cappio F.
- HS1 has a central role in the trafficking and homing of leukemic B cells. Blood. 2010 Nov 4;116(18):3537-46; 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 complexes with cytoskeleton adapters in normal and malignant chronic lymphocytic leukemia B cells. Leukemia. 2007 Sep;21(9):2067-70; Muzio M*, Scielzo C*, Frenquelli M, Bachi A, De Palma M, Alessio M, Ghia P, Caligaris-Cappio F. * authors equally contributed
- 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; Scielzo C, Ghia P, Conti A, Bachi A, Guida G, Geuna M, Alessio M, Caligaris-Cappio F.