The group is in charge of the Reverse Phase Protein Arrays (RPPA) facility that allows the identification of new disease biomarkers and new therapeutic targets in oncological and non-oncological diseases through phosphoproteomic profiling. To do so we dispose of a library of more than 130 validated antibody belonging to the most deregulated pathways in cancer and inflammation, and a full equipped facility for sample preparation, slides printing and staining. We believe that monitoring the activation status of signal transduction pathways will be key to identify patient subgroups that can benefit from the use of specific kinase inhibitors and to point out proteins suitable for patient risk stratification and targeted therapy. In recent years through RPPA we identified and then validated new potential biomarkers and therapeutic targets for B and T Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML) and T cell Acute Lymphoblastic Lymphoma pediatric patients (T LBL).
In particular, on-going projects include:
i) identification of new glucocorticoid resistance mechanisms in T ALL pediatric patients: in the past three years our research mainly focused on the study of molecular mechanisms responsible of glucocorticoid resistance in T ALL pediatric patients. Indeed, we observed the hyperactivation of LCK kinase in patients more resistant to glucocorticoids and in ETP T ALL, a subset of patients highly resistant to therapy (Serafin V. et al, Blood 2017). The pharmacological inhibition or the specific gene silencing of this kinase in glucocorticoid resistant cells turn them sensitive to corticosteroids both in vitro and in vivo (Serafin V. et al, Leukemia 2017). Starting from these evidences we are now studying more in deep the molecular mechanisms underlying the glucocorticoid resistance in this subset of pa-tients (Supported by AIRC “My First AIRC Grant” and FUV).
ii) identification of new biomarkers and therapeutic targets in the Graft vs Host Disease: another field of study of our group regards the research of new potential biomarkers and therapeutic targets in the Graft versus Host Disease (GvHD). Specifically, we focused on the study of the Chronic (cGvHD) form since the diagnosis is based only on physical examination and, when possible, histo-pathological confirmation. The finding of novel biomarkers for the diagnosis of cGvHD could be used together with standard criteria to significantly improve the diagnosis of this disease. (Supported by IRP)
The group is also involved in several national and international collaborative studies focused on the phosphoproteomic profiling of different neoplastic and non-neoplastic diseases. In particular, thanks to a collaboration with Prof. Sandra Marmiroli of the University of Modena and Reggio Emilia we are also investigating the metabolic profile of specific T ALL pediatric subgroups and studying a combined metabolic and signaling inhibition approach for the treatment of these patients
Giulia Veltri, PhD student
Fang C, Wang Z, Han C, Safgren SL, Helmin KA, Adelman ER, Serafin V, Basso G, Eagen KP, Gaspar-Maia A, Figueroa ME, Singer BD, Ratan A, Ntziachristos P, Zang C. Cancer-specific CTCF binding facilitates oncogenic transcriptional dysregulation. Genome Biol. 2020 Sep 15;21(1):247;
Zhou Y, Han C, Wang E, Lorch AH, Serafin V, Cho BK, Gutierrez Diaz BT, Calvo J, Fang C, Khodadadi-Jamayran A, Tabaglio T, Marier C, Kuchmiy A, Sun L, Yacu G, Filip SK, Jin Q, Takahashi YH, Amici DR, Rendleman EJ, Rawat R, Bresolin S, Paganin M, Zhang C, Li H, Kandela I, Politanska Y, Abdala-Valencia H, Mendillo ML, Zhu P, Palhais B, Van Vlierberghe P, Taghon T, Aifantis I, Goo YA, Guccione E, Heguy A, Tsirigos A, Wee KB, Mishra RK, Pflumio F, Accordi B, Basso G, Ntziachristos P. Posttranslational regulation of the exon skipping machinery controls aberrant splicing in leukemia [published online ahead of print, 2020 May 22]. Cancer Discov. 2020;CD-19-1436;
Serafin V, Porcù E, Cortese G, Mariotto E, Veltri G, Bresolin S, Basso G, Accordi B. SYK Targeting Represents a Potential Therapeutic Option for Relapsed Resistant Pediatric ETV6-RUNX1 B-Acute Lymphoblastic Leukemia Patients. Int J Mol Sci. 2019 Dec 7;20(24):6175;
Jin Q, Martinez CA, Arcipowski KM, Zhu Y, Gutierrez-Diaz BT, Wang KK, Johnson MR, Volk AG, Wang F, Wu J, Grove C, Wang H, Sokirniy I, Thomas PM, Goo YA, Abshiru NA, Hijiya N, Peirs S, Vandamme N, Berx G, Goosens S, Marshall SA, Rendleman EJ, Takahashi YH, Wang L, Rawat R, Bartom ET, Collings CK, Van Vlierberghe P, Strikoudis A, Kelly S, Ueberheide B, Mantis C, Kandela I, Bourquin JP, Bornhauser B, Serafin V, Bresolin S, Paganin M, Accordi B, Basso G, Kelleher NL, Weinstock J, Kumar S, Crispino JD, Shilatifard A, Ntziachristos P. USP7 Cooperates with NOTCH1 to Drive the Oncogenic Transcriptional Program in T-Cell Leukemia. Clin Cancer Res. 2019;25(1):222-239;
De Smedt R, Peirs S, Morscio J, Matthijssens F, Roels J, Reunes L, Lintermans B, Goossens S, Lammens T, Van Roy N, Touzart A, Jenni S, Tsai YC, Lovisa F, Mussolin L, Serafin V, Van Nieuwerburgh F, Deforce D, Uyttebroeck A, Tousseyn T, Burkhardt B, Klapper W, De Moerloose B, Benoit Y, Macintyre E, Bourquin JP, Basso G, Accordi B, Bornhauser B, Meijerink J, Vandenberghe P, Van Vlierberghe P.Pre-clinical evaluation of second generation PIM inhibitors for the treatment of T-cell acute lymphoblastic leukemia and lymphoma. Haematologica. 2019;104(1):e17-e20;
Zampini M, Tregnago C, Bisio V, Simula L, Borella G, Manara E, Zanon C, Zonta F, Serafin V, Accordi B, Campello S, Buldini B, Pession A, Locatelli F, Basso G, Pigazzi M. Epigenetic heterogeneity affects the risk of relapse in children with t(8;21)RUNX1-RUNX1T1-rearranged AML. Leukemia. 2018 May;32(5):1124-1134;
Serafin V, Capuzzo G, Milani G, Minuzzo SA, Pinazza M, Bortolozzi R, Bresolin S, Porcù E, Frasson C, Indraccolo S, Basso G, Accordi B. Glucocorticoid resistance is reverted by LCK inhibition in pediatric T-cell acute lymphoblastic leukemia. Blood. 2017 Dec 21;130(25):2750-2761;
Serafin V, Lissandron V, Buldini B, Bresolin S, Paganin M, Grillo F, Andriano N, Palmi C, Cazzaniga G, Marmiroli S, Conter V, Basso G, Accordi B. Phosphoproteomic analysis reveals hyperactivation of mTOR/STAT3 and LCK/Calcineurin axes in pediatric early T-cell precursor ALL. Leukemia. 2017;31(4):1007-1011;
Tumino M, Serafin V, Accordi B, Spadini S, Forest C, Cortese G, Lissandron V, Marzollo A, Basso G, Messina C. Interleukin-22 in the diagnosis of active chronic graft-versus-host disease in paediatric patients. Br J Haematol. 2015 Jan;168(1):142-5;
Ghisi M, Corradin A, Basso K, Frasson C, Serafin V, Mukherjee S, Mussolin L, Ruggero K, Bonanno L, Guffanti A, De Bellis G, Gerosa G, Stellin G, D’Agostino DM, Basso G, Bronte V, Indraccolo S, Amadori A, Zanovello P. Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150. Blood. 2011 Jun 30;117(26):7053-62;