MembersCatapano Carlo, MD, PhD, Group Leader
Civenni Gianluca, PhD
Federici Elisa, Stage
Giugni Nicole, MS Stage (tesista)
Merulla Jessica, PhD
Mosole Simone, Research Assistant (immunohistochemistry)
Sandrini Giada, PhD Student
Storelli Elisa, Research Assistant
Uboldi Valeria, PhD Student
Current objectives of the research in my group are the investigation of transcriptional, epigenetic and metabolic mechanisms in cancer stem cells and the development of innovative therapeutic strategies.
Transcription factors are central nodes in multiple oncogenic pathways and represent attractive targets for development of new cancer therapeutics. However, very few direct pharmacological inhibitors of transcription factors are currently available. My group is investigating various approaches, including small molecule inhibitors, small interfering RNAs and oligonucleotides, to block the activity of oncogenic transcription factors.
Extensive modifications of the epigenetic landscape occur along with deregulated activity of transcription factors and are at the basis of the phenotypic reprogramming associated with tumor initiation, progression and treatment failure. We are investigating the role of epigenetic regulators in stemness, tumor progression and treatment resistance and the impact of specific inhibitors on these processes. Novel epigenetic effectors, such as promoter-associated long noncoding RNAs (paRNAs) and miRNAs, are investigated as potential targets for innovative therapeutic strategies.
Stem-like tumor cells or cancer stem cells are emerging as important players in metastatic progression and treatment failure. It is becoming evident that it is necessary to block the cancer stem-like cell subpopulation in order to have an effective and lasting impact on the disease. We are investigating the biological pathways responsible for self-renewal, expansion and maintenance of stem-like tumor cells in human cancers. Our attention goes to the processes that sustain the stem-like phenotype through transcriptional, epigenetic and metabolic reprogramming. To this end, we have established protocols to study cancer stem cells in multiple experimental models in vitro and in vivo. Using these models, we are studying specific features of cancer stem cells and test inhibitors of key pathways to establish their potential for therapeutic applications.
- Targeting metabolic reprogramming and plasticity of cancer stem cells to impact on tumor progression and treatment resistance (SNSF 310030L_170182)
- Epigenetic cross-talks and novel therapeutic strategies to prevent disease progression in ERG fusion positive prostate cancer (SNSF IZLSZ3_170898)
- Cancer Nanomedicine: from the bench to the bedside. Nano2Clinic. COST Action https://www.nano2clinic.eu/
- Targeting mitochondrial dynamics and cancer cell plasticity in prostate cancer
- Preclinical Modeling of Cancer Stem Cell Directed Therapies
- Promoter proximal long noncoding RNA and epigenetic regulatory networks in human cancer
- Targeting Lin28-dependent cancers
- Structural basis for the inhibition of STAT3 transcription factor by small molecules
- Biological and genetic determinants of response to transcriptional inhibitors in human cancers
- Novel epigenetic targets for cancer therapy
- Civenni G, Albino D, Shinde D, Vázquez R, Merulla J, Kokanovic A, Mapelli SN, Carbone GM, Catapano 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.
- 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 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.
- 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.
- Shinde D, Albino D, Zoma M, Mutti A, Mapelli SN, Civenni G, Kokanovic A, Merulla J, Perez-Escudero J, Costales P, Moris F, Catapano CV, Carbone GM. Transcriptional Reprogramming and Inhibition of Tumor-propagating Stem-like Cells by EC-8042 in ERG-positive Prostate Cancer. Eur Urol Oncol 2018org/10.1016/j.euo.2018.08.024.
- 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 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.
- Sgrignani J, Garofalo M, Matkovic M, Merulla J, Catapano CV, Cavalli A. Structural Biology of STAT3 and Its Implications for Anticancer Therapies Development. Int J Mol Sci. 2018 May 28;19(6). pii: E1591. doi:10.3390/ijms19061591. Review. PubMed PMID: 29843450; PubMed Central PMCID: PMC6032208.
- 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 A promoter-proximal transcript targeted by genetic polymorphism controls E-cadherin silencing in human cancers. Nat Commun. 2017 May 30;8:15622.
- Genini D, Brambilla L, Laurini E, Merulla J, Civenni G, Pandit S, D’Antuono R,Perez L, Levy DE, Pricl S, Carbone GM, Catapano 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.
- Napoli S, Piccinelli V, Mapelli S, Pisignano G, Catapano Natural antisense transcripts drive a regulatory cascade controlling c-MYC transcription. RNA Biol. 2017 Aug 14:0. doi: 10.1080/15476286.2017.1356564.