Members.Giuseppina Carbone, MD, Head
Alessia Cacciatore, MS student
Alessio Fusina, MS student
Dheeraj Shinde, PhD
Domenico Albino, PhD
Elisa Sorrenti, MS student
Simone Mosole, Research Assistant
Valeria Uboldi, MS student
Research in our group is focused on the study of the molecular mechanisms that control prostate cancer development and progression. Cancer of the prostate is the most common cancer and one of leading causes of cancer related death. At the present there is a need to understand the mechanisms involved in the pathogenesis of this disease and find the means to distinguish between cancers that may need different therapeutic strategies. One of our goals is to identify and characterize the transcription factor cascade that control prostate cancer development. Cell growth and differentiation processes are regulated at the level of gene transcription. Many transcription factors possess transforming potential when expressed in a deregulated fashion. ETS factors constitute a network of transcriptional regulators that activate or repress the expression of genes that are involved in various biological processes, including cellular proliferation, apoptosis, invasiveness and cancer progression. The laboratory has identified ETS genes potentially involved in prostate cancer, based upon their altered expression in prostate cancer clinical samples. Currently, the functional role of these genes is being investigated as well as their relevance for diagnosis, prognosis and therapy. We are also investigating novel therapeutic approaches to target oncogenic ETS factors.
Current active projects – PI: Giuseppina Carbone, MD
Project Title: The ETS transcription factor ESE3/EHF as a regulator of prostate epithelial cell differentiation and stem cell properties.
Swiss National Science Foundation (SNSF). 310030_189081. 2019-2023 (48 months). PI: Carbone GM.
Total Awarded: CHF 707’200.
The newly funded project will continue the effort of the Prostate Cancer Biology group toward a comprehensive understanding of the tumor suppressor role of ESE3/EHF transcription factor in prostate gland development and tumorigenesis. We propose that this epithelial-restricted transcription factor is an important barrier to malignant transformation and tumor progression in the prostate. We plan to integrate multiple genomic approaches to address the role of ESE3/EHF in the transcriptional and epigenetic reprogramming that defines prostate epithelial cell differentiation and sets the basis for malignant transformation. To this end, we will perform in cellular and mouse models bulk and single-cell RNA-seq studies to determine ESE3/EHF dependent cell-specific expression patterns, ChIP-seq to map genomic distribution of ESE3/EHF and other transcription factors, along with ATAC-seq and Hi-C to define accessibility and functional organization of the genome. This project will provide important new insights with a high potential to impact on clinical management of prostate cancer patients.
Project Title: Biological and clinical impact of epigenetic cross-talks in ERG fusion positive prostate cancers
Oncosuisse/Swiss Cancer League (KLS). KLS-4569. 2018-2020 (24 months). PI: Carbone GM.
Total Awarded: CHF 246’050.
The overall goal of this project is to understand the mechanisms involved in ERG oncogenic activation in prostate cancer and its role in epigenetic reprogramming. To this end, we will combine molecular, genomic and functional studies in cell cultures and animal models. Collectively, the combination of molecular and cellular biology approaches along with the availability of transgenic and knockout mice, human and mouse engineered cell lines will lead to a deep understanding of the biological mechanisms underlying ERG-dependent tumorigenesis.
Project title: Epigenetic cross-talks and novel therapeutic strategies to prevent disease progression in ERG fusion positive prostate cancer.
Swiss National Science Foundation (SNSF). IZLSZ3_170898 2016-2020. PIs: Catapano, Zerbini, Carbone.
This project is a collaborative effort to study the role of transcription factors, epigenetic effectors and co-activators in prostate cancer progression.
- The ETS transcription factor ESE3/EHF as a regulator of prostate epithelial cell differentiation and stem cell properties.
- Functional, clinical and therapeutic impact of epigenetic cross-talks in ERG fusion positive prostate cancers.
- MicroRNA network regulated by ETS transcription factors in prostate cancer
Dr. Giuseppina Carbone, is a member of the European Association of Urology (EAU). She has been approved by the EAU as Host for the European Urological Scholarship Programme (EUSP) for training young urologists in laboratory research.
The IOR is now a certified EBU-EAU Host Centre in the field of Prostate Cancer. Applicants for the EUSP Scholarships are urologists or urologists-in-training (third or fourth year resident) under 40 years old with an interest in clinical/laboratory research and an academic position.
Conditions for application:
- Applicants for the EUSP Scholarship must be urologists or urologists-in-training (third or fourth year resident)
- EAU membership for at least one year is mandatory
- Under 40 years old
- Interest in an academic position
Application deadlines: 1 January, 1 May and 1 September of each year
For further details please visit the website www.uroweb.org/education/career-development/scholarship
For information about the center follow the link EBU Certified Centres
Swiss National Science Foundation (SNSF) PI,Giuseppina M Carbone Title: The ETS transcription factor ESE3/EHF as a regulator of prostate epithelial cell differentiation and stem cell properties
Oncosuisse/Swiss Cancer League PI, Giuseppina M Carbone Title: Biological and clinical impact of epigenetic cross-talks in ERG fusion positive prostate cancers
Comprehensive Publication list
- Civenni G, Bosotti R, Timpanaro A, Vàzquez R, Merulla J, Pandit S, Rossi S, Albino D, Allegrini S, Mitra A, Mapelli SN, Vierling L, Giurdanella M, Marchetti M, Paganoni A, Rinaldi A, Losa M, Mira-Catò E, D’Antuono R, Morone D, Rezai K, D’Ambrosio G, Ouafik L, Mackenzie S, Riveiro ME, Cvitkovic E, Carbone GM, Catapano CV. Epigenetic control of mitochondrial fission enables self-renewal of stem-like tumor cells in human prostate cancer. Cell Metab. 2019 May 20. doi:10.1016/j.cmet.2019.05.004.
- Civenni G, Albino D, Shinde D, Vázquez R, Merulla J, Kokanovic A, Mapelli SN, Carbone GM, Catapano CV. Transcriptional Reprogramming and Novel Therapeutic Approaches for Targeting Prostate Cancer Stem Cells. Front Oncol. 2019 May 9;9:385. doi: 10.3389/fonc.2019.00385.
- Mapelli, S.N., Napoli, S., Pisignano, G., Garcia-Escudero, R., Carbone, G.M., and Catapano, C.V. Deciphering the complexity of human noncoding promoter-proximal transcriptome. Bioinformatics. 2018 Dec 10. doi: 10.1093/bioinformatics/bty981.
- Scimeca M, Urbano N, Bonfiglio R, Mapelli SN, Catapano CV, Carbone GM, Ciuffa S, Tavolozza M, Schillaci O, Mauriello A, Bonanno E. Prostate Osteoblast-Like Cells: A Reliable Prognostic Marker of Bone Metastasis in Prostate Cancer Patients. Contrast Media Mol Imaging. 2018 Dec 9;2018:9840962. doi: 10.1155/2018/9840962.
- Civenni G, Carbone GM, Catapano CV. Overview of Genetically Engineered Mouse Models of Prostate Cancer and Their Applications in Drug Discovery. Curr Protoc Pharmacol. 2018 Jun;81(1):e39. doi: 10.1002/cpph.39.
- Dheeraj Shinde, Domenico Albino, Marita Zoma, Azzurra Mutti, Sarah N. Mapelli, Gianluca Civenni, Aleksandra Kokanovic, Jessica Merulla, Jhudit Perez-Escuredo, Paula Costales,Francisco Morìs, Carlo V. Catapano, Carbone G.M.Transcriptional reprogramming and inhibition of tumor-propagating stem-like cells by EC-8042 in ERG-positive prostate cancer. Eur Urol Oncol,doi.org/10.1016/j.euo.2018.08.024.
- Sarah N. Mapelli, Sara Napoli, Giuseppina Pisignano, Ramon Garcia-Escudero, Giuseppina M. Carbone and Carlo V. Catapano. Deciphering the complexity of human noncoding promoter-proximal transcriptome.Bioinformatics,2018 doi: 10.1093/bioinformatics/bty981.
- Manuel Scimeca, Nicoletta Urbano, Rita Bonfiglio, Sarah N. Mapelli, Carlo V. Catapano, Giuseppina M. Carbone, Sara Ciuffa, Orazio Schillaci, Alessandro Mauriello and Elena Bonanno. Prostate osteoblast-like cells: a reliable prognostic marker of bone metastasis in prostate cancer patients. Contrast Media & Molecular Imaging, Dec 9;2018:9840962. doi: 10.1155/2018/9840962.
- Civenni G, Carbone G.M., and Catapano CV. Genetically Engineered Mouse Models of Prostate Cancer and their Applications in Drug Discovery. Current Protocols in Pharmacology,2018.
- Pisignano G,Napoli S, Magistri M,Mapelli SN, Pastori C, Di Marco S, Civenni G, Albino D, Enriquez C, Allegrini S, Mitra A, D’Ambrosio G, Mello-Grand M, Chiorino G, Garcia-Escudero R,Varani G, Carbone GM, Catapano CV. A promoter-proximal transcript targeted by genetic polymorphism controls E-cadherin silencing in human cancers.Nat Commun 2017 May 30;8:15622. doi: 10.1038/ncomms15622
- Genini D,Brambilla L,Laurini E, Merulla J, Civenni G, Pandit S,D’Antuono R, Perez L, Levy DE, Pricl S, Carbone GM, Catapano CV. Mitochondrial dysfunction induced by a SH2 domain-targeting STAT3 inhibitor leads to metabolic synthetic lethality in cancer cells. Proc Natl Acad Sci U S A. 2017 Jun 20;114(25):E4924-E4933. doi: 10.1073/pnas.1615730114. Epub 2017 Jun 5.
- Dallavalle C, Albino D, Civenni G, Merulla J, Ostano P, Mello-Grand M, Rossi S, Losa M, D’Ambrosio G, Sessa F, Thalmann GN, Garcia-Escudero R, Zitella A, Chiorino G, Catapano CV, Carbone GM. J Clin Invest. 2016 Nov 7. pii: 86505. doi: 10.1172/JCI86505.
- Albino D, Civenni G, Rossi S, Catapano CV, Carbone GM. The ETS factor ESE3/EHF represses IL-6 and restrains prostate cancer stem–like compartment. 2016 Oct 8. doi: 10.18632/oncotarget.12525.
- Albino D, Civenni G, Dallavalle C, Roos M, Jahns H, Curti L, Rossi S, Pinton S, D’Ambrosio G, Sessa F, Hall J, Catapano CV, Carbone GM. Activation of the Lin28/let-7 Axis by Loss of ESE3/EHF Promotes a Tumorigenic and Stem-like Phenotype in Prostate Cancer. Cancer Res. 2016 Jun 15;76(12):3629-43. doi: 10.1158/0008-5472.CAN-15-2665. Epub 2016 May 2. PubMed PMID: 27197175.
- Gianluca Civenni, Nicole Longoni, Paula Costales, Cecilia Dallavalle, Cristina García Inclán, Domenico Albino, Luz Elena Nuñez, Francisco Morís2, Giuseppina M. Carbone and Carlo V. Catapano. EC-70124, a novel glycosylated indolocarbazole multi-kinase inhibitor, reverts tumorigenic and stem cell properties in prostate cancer by inhibiting STAT3 and NF-κB. Molecular Cancer Ther,15,5 2016.
- Brambilla L, Genini D, Laurini E, Merulla J, Perez L, Fermeglia M, Carbone GM, Pricl S, Catapano CV. Hitting the right spot: Mechanism of action of OPB-31121, a novel and potent inhibitor of the Signal Transducer and Activator of Transcription 3 (STAT3). Mol Oncol. 2015 Mar pii: S1574-7891(15)00048-4. doi: 10.1016/j.molonc.2015.02.012
- Madhuri Kalathur, Alberto Toso, Jingjing Chen, Ajinkya Revandkar, Claudia Danzer-Baltzer, Ilaria Guccini, Abdullah Alajati, Manuela Sarti, Sandra Pinton, Lara Brambilla, Diletta Dimitri, Giuseppina Carbone, Ramon Garcia-Escudero, Alessandro Padova, Letizia Magnoni, Alessia Tarditi, Laura Maccari, Federico Malusa, Ravi Kiran Kalathur, Lorenzo Pinna, Maria Ruzzene, Giorgio Cozza, Carlo Catapano, Ian Frew, Nicolas Delaleu and Andrea Alimonti. A chemogenomic and shRNA screenings identify CK2 as a novel target for pro-senescence therapy in PTEN deficient tumors. Nature Communication, 2015.
- Sarti M, Pinton S, Limoni C, Carbone GM, Pagani O, Cavalli F, Catapano CV.Differential expression of testin and survivin in breast cancer subtypes. Oncol Rep. 2013 Aug;30(2):824-32.
- Longoni N, Sarti M, Albino D, Civenni G, Malek A, Ortelli E, Pinton S, Mello-Grand M, Ostano P, D’Ambrosio G, Sessa F, Garcia-Escudero R, Thalmann GN, Chiorino G, Catapano CV, Carbone GM. The ETS Transcription Factor ESE1/ELF3 Orchestrates a Positive Feedback Loop That Constitutively Activates NF-κB and Drives Prostate Cancer Progression. Cancer Res. 2013 Jul 15;73 (14):4533-47.
- Civenni G., Malek A., Albino D., Garcia-Escudero R., Napoli S., Di Marco S., Pinton S., Sarti M., Carbone G.M, Catapano, C.V. RNAi-mediated silencing of Myc transcription inhibits stem-like cell maintenance and tumorigenicity in prostate cancer. Cancer Res. 2013; 73(22): 6816-27.
- Albino D, Longoni N, Curti L, Mello-Grand M, Pinton S, Civenni G, Thalmann G, D’Ambrosio G, Sarti M, Sessa F, Chiorino G, Catapano CV, Carbone GM. ESE3/EHF controls epithelial cell differentiation and its loss leads to prostate tumors with mesenchymal and stem-like features. Cancer Res. 2012 Jun 1;72(11):2889-900.
- Longoni N, Kunderfranco P, Pellini S, Albino D, Mello-Grand M, Pinton S, D’Ambrosio G, Sarti M, Sessa F, Chiorino G, Catapano CV, Carbone GM. Aberrant expression of the neuronal-specific protein DCDC2 promotes malignant phenotypes and is associated with prostate cancer progression. 2012 Jun 25. doi: 10.1038/onc.2012.245.
- Malek A, Núñez LE, Magistri M, Brambilla L, Jovic S, Carbone GM, Morís F, Catapano CV. Modulation of the activity of Sp transcription factors by mithramycin analogues as a new strategy for treatment of metastatic prostate cancer. PLoS One. 2012;7(4):e35130.
- Babbio F, Pistore C, Curti L, Castiglioni I, Kunderfranco P, Brino L, Oudet P, Seiler R, Thalman GN, Roggero E, Sarti M, Pinton S, Mello-Grand M, Chiorino G, Catapano CV, Carbone GM, Bonapace IM. The SRA protein UHRF1 promotes epigenetic crosstalks and is involved in prostate cancer progression. 2012 Nov 15;31(46):4878-87.
- Carmen Jerónimo, Patrick J. Bastian, Anders Bjartell, Giuseppina M. Carbone, James W.F. Catto, Susan J. Clark, Rui Henrique, Francesco Montorsi, William G.Nelson, Shahrokh F. Shariat. (2011) Epigenetics in Prostate Cancer: biological and clinical relevance. European Urology 2011 Oct;60(4):753-66.
- Genini D, Garcia-Escudero R, Carbone GM, Catapano CV. Transcriptional and Non-Transcriptional Functions of PPARβ/δ in Non-Small Cell Lung Cancer. 2012;7(9):e46009.
- Kunderfranco, P., Mello-Grand, M., Cangemi, R., Pellini, S., Mensah, A., Albertini, V., Malek, A., Chiorino, G., Catapano, C.V. and Carbone, G.M. ETS transcription factors control transcription of EZH2 and epigenetic silencing of the tumor suppressor gene Nkx3.1 in prostate cancer. PLoS One 5, e10547 (2010).
- Pastori, C., Magistri, M., Napoli, S., Carbone, G.M. & Catapano, C.V. Small RNA-directed transcriptional control: New insights into mechanisms and therapeutic applications. Cell Cycle 9, 2353-2362 (2010).
- Previdi, S., Malek, A., Albertini, V., Riva, C., Capella, C., Broggini, M., Carbone, G.M., Rohr, J. & Catapano, C.V. Inhibition of Sp1-dependent transcription and antitumor activity of the new aureolic acid analogues mithramycin SDK and SK in human ovarian cancer xenografts. Gynecol Oncol 118, 182-188 (2010).
- Jain A, Magistri M, Napoli S, Carbone GM and Catapano C.V. Mechanisms of Triplex DNA-mediated Inhibition of Transcription Initiation in Cells. Biochemie 2010.
- Napoli S, Pastori C, Magistri M, Carbone GM, Cavalli F. and Catapano C.V. Promoter-specific transcriptional interference and c-myc gene silencing by siRNAs in human cells. EMBO J. 2009 Jun 17;28(12):1708-19. Epub 2009 May 21.
- Genini D, Carbone GM and Catapano C.V. (2008) Multiple Interactions between Peroxisome Proliferators-Activated Receptors and the Ubiquitin-Proteasome System and Implications for Cancer Pathogenesis. PPAR Res, 2008, 195065.
- Romina Cangemi, Afua Mensah, Veronica Albertini, Maurizia Mello-Grand, Giovanna Chiorino, Carlo V. Catapano and Giuseppina Carbone. Reduced expression and tumor suppressor function of the ETS transcription factor ESE-3 in prostate cancer. Oncogene 27, 2877-2885,2007.
- Sara Vignati, Veronica Albertini, Andrea Rinaldi, Ivo Kwee, Cristina Riva, Rita Oldrini, Carlo Capella, Francesco Bertoni, Giuseppina M. Carbone and Carlo V. Catapano. Cellular and molecular consequences of peroxisome proliferator-activated receptor-gamma activation in ovarian cancer cells. Oct;8 (10):851-61 (2007).
- Veronica Albertini, Aklank Jain, Sara Vignati, Sara Napoli, Andrea Rinaldi, Ivo Kwee, Mohammad Nur-e-Alam, Julia Bergant, Francesco Bertoni, Giuseppina M. Carbone, Jurgen Rohr and Carlo V. Catapano. Novel GC-rich DNA binding compound produced by a genetically engineered mutant of the mithramyicin producer Argillaceus exhibits improved transcriptional repressor activity: implications for cancer therapy. Nucleic Acid. Res. 34(6): 1721-34, (2006).
- Napoli S, Negri U, Arcamone F, Capobianco ML, Carbone GMR, Catapano CV. Growth inhibition and apoptosis induced by daunomycin-conjugated triplex-forming oligonucleotides targeting the c-myc gene in prostate cancer cells. Nucleic Acids Res. 34(2):734-44 (2006).
- Carbone GMR, Napoli S, Valentini A, Cavalli F, Watson DK, Catapano CV. Triplex DNA-mediated downregulation of Ets2 expression results in growth inhibition and apoptosis in human prostate cancer cells. Nucleic Acid Res.32(14):4358-67(2005)
- Sara Napoli, Carbone GMR, Carlo Catapano, Nick Shaw, and Dev. P. Arya. Neomycin improves cationic lipid-mediated transfection of DNA in human cells. Bioorg Med Chem Lett. 2005 Jul 15;15 (14):3467-9.
- Carbone GMR, Collier A, McGuffie EM, Catapano CV. Selective inhibition of transcription of the Est2 gene in prostate cancer cells by a triplex-forming oligonucleotide. Nucleic Acids Res. 31: 833-843 (2003).
- Remsing LL, Bahadori HR, Carbone GMR, McGuffie EM, Catapano CV, Rohr J. Inhibition of c-src transcription by mithramycin: structure-activity relationships of biosynthetically produced mithramycin analogues using the c-src promoter as target. Biochemistry 42: 8313-8324 (2003).
- Carbone GMR, McGuffie EM,NapoliS,Flanagan CE,Dembech C,Negri U,Arcamone F,Capobianco ML,and Catapano CV. DNA binding and antigene activity of a daunomycin-conjugated triplex-forming oligonucleotide targeting the P2 promoter of the human c-myc gene.Nucleic.Acid Res. 32(8):2396-410 (2004).
- Carbone GMR, Napoli S, Valentini A, Cavalli F, Watson DK, Catapano CV. Triplex DNA-mediated downregulation of Ets2 expression results in growth inhibition and apoptosis in human prostate cancer cells. Nucleic Acid Res.32(14):4358-67(2004)
- Carbone GMR, Catapano CV, Fernandes DJ: Imbalanced DNA synthesis induced by cytosine arabinoside and fludarabine in human leukemia cells. Biochem. Pharmacol., 62 (2001) 101-110.
- Catapano CV, Pacheco D, McGuffie EM, Carbone GMR: Inhibition of gene expression and cell proliferation by triple helix-forming oligonucleotides directed to the c-myc gene. Biochemistry 39:5126-5138 (2000).
- McGuffie EM, Pacheco D, Carbone GMR, Catapano CV: Antigene and antiproliferative effects of a c-myc-targeting phosphorothioate triple helix-forming oligonucleotides in human leukemia cells. Cancer Res 60:3790-3799 (2000).
- Catapano CV, Carbone GMR, Pisani F, Fernandes DJ: Arrest of replication fork progression at sites of VM-26-stabilized topoisomerase II-DNA complex formation in human CEM leukemia cells. Biochemistry 36:5739-5748 (1997).
- Catapano CV, Carbone GMR, Fernandes DJ: The nuclear matrix as a target for cancer therapy. Annals of Oncol 7:659-666 (1996).
- Carbone GMR, Sheikh AU, Zehnder T, Rose JC: Effect of chronic infusion of cortisol on renin gene expression and renin response to hemorrhage in fetal lambs at 0.65 gestation. Pediatr Res 37:316-20 (1995).
- Carbone GMR, St. Clair DK, Xu YA, Rose JC: Expression of manganese superoxide dismutase in ovine kidney cortex during development. Pediatr Res 35:41-4 (1994).
- Carbone GMR, Sheik AU, Rogers S, Brewer G, Rose JC: Developmental changes in renin gene expression in ovine kidney cortex. Am J Physiol 264:R591-596 (1993).