The concept that small non-coding RNAs namely miRNAs, are involved in tumorigenesis, particularly in chronic lymphocytic leukemia (CLL) was pioneered during the last few years, in the laboratory of Dr. Croce. As an active member of this group, I contributed to the identification of an important miRNA-related mechanism of leukemogenesis, by discovering that the Bcl2 protein was a target of miRs 15a-16-1. This study was fundamental for the understanding of CLL pathogenesis and has fostered the development of a drug capable to cure CLL. Very recently, a specific BCL2 inhibitor ABT-199 (Venetoclax) was developed and approved by FDA for CLL treatment.  In 2007 we also provided the evidence  that another family of ncRNAs named ultraconserved genes (UCGs) are involved in human cancers and directly interact with miRNAs .My research is now based on the identification of a panel of  transcribed ultraconserved RNA  (T-UCRs) having  distinct “peaks” of expression in low- and high-grade Bladder cancer (BlCa) tissues  that will be able to recognize all histotypes of bladder cancer. The selected panel  can be detected – and precisely quantified using digital real time  on the tumor cells exfoliate in the urine samples. Then, with the measure  of T-UCRs biomarkers in urine , we will provide  an  approach based on a non-invasive, easy to perform, rapid and and accurate test to be widely used in clinical practice for early detection and follow-up of BlCa. 

Terreri S, Mancinelli S, Ferro M, Vitale MC, Perdonà S, Castaldo L, Gigantino V, Mercadante V, De Cecio R, Aquino G, Montella M, Angelini C, Del Prete E, Aprile M, Ciaramella A, Liguori GL, Costa V, Calin GA, La Civita E, Terracciano D, Febbraio F, Cimmino A. Subcellular Localization of uc.8+ as a Prognostic Biomarker in Bladder Cancer Tissue. Cancers (Basel). 2021 Feb 8;13(4):681. doi: 10.3390/cancers13040681. PMID: 33567603; PMCID: PMC7914980.

Vannini I, Wise PM, Challagundla KB, Plousiou M, Raffini M, Bandini E, Fanini F, Paliaga G, Crawford M, Ferracin M, Ivan C, Fabris L, Davuluri RV, Guo Z, Cortez MA, Zhang X, Chen L, Zhang S, Fernandez-Cymering C, Han L, Carloni S, Salvi S, Ling H, Murtadha M, Neviani P, Gitlitz BJ, Laird-Offringa IA, Nana-Sinkam P, Negrini M, Liang H, Amadori D, Cimmino A, Calin GA, Fabbri M.  “Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs.” Nature communications vol. 8,1 1801. 27 Nov. 2017, doi:10.1038/s41467-017-01562-9

Fabbri M, Bottoni A, Shimizu M, Spizzo R, Nicoloso MS, Rossi S, Barbarotto E, Cimmino A, Adair B, Wojcik SE, Valeri N, Calore F, Sampath D, Fanini F, Vannini I, Musuraca G, Dell’Aquila M, Alder H, Davuluri RV, Rassenti LZ, Negrini M, Nakamura T, Amadori D, Kay NE, Rai KR, Keating MJ, Kipps TJ, Calin G*, Croce CM*. Association of a microRNA/TP53 feedback circuitry with pathogenesis and outcome of B-cell chronic lymphocytic leukemia. JAMA. 2011 Jan 5;305(1):59-67. doi: 10.1001/jama.2010.1919. PubMed PMID: 21205967. The identification of a complex network of miRNAs and coding genes influencing the natural history of the most frequent type of leukemia in the western World.

Calin G, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM.  A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005 Oct 27;353(17):1793-801. PubMed PMID: 16251535. The discovery of germline mutations located in the cluster miR-15a/16 in human cancers, including familial cases with CLL and breast cancers.Calin G, Liu CG, Ferracin M, Hyslop T, Spizzo R, Sevignani C, Fabbri M, Cimmino A, Lee EJ, Wojcik SE, Shimizu M, Tili E, Rossi S, Taccioli C, Pichiorri F, Liu X, Zupo S, Herlea V, Gramantieri L, Lanza G, Alder H, Rassenti L, Volinia S, Schmittgen TD, Kipps TJ, Negrini M, Croce CM.  Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell. 2007 Sep;12(3):215-29. PubMed PMID: 17785203. The identification of a new family of non-codingRNAs involved in cancers – the ultraconserved genes, that did not change sequence in hundreds of millions of years of evolution.

Cimmino, Amelia et al. “miR-15 and miR-16 induce apoptosis by targeting BCL2.” Proceedings of the National Academy of Sciences of the United States of America vol. 102,39 (2005): 13944-9. doi:10.1073/pnas.0506654102. This study was fundamental for the understanding of chronic lymphocytic leukemia (CLL) pathogenesis and has fostered the development of a drug capable to cure CLL. Very recently, a specific BCL2 inhibitor ABT-199 (Venetoclax) was developed and approved by FDA for CLL treatment.

31/October/1996

M.D. Degree from School of Medicine and Surgery, Federico II University, Naples

1996-2000

Residency and Specialization Degree in Clinical Chemistry and Biochemistry and Molecular Biology. School of Medicine and Surgery, S.U.N., Italy. 

21 / December /2004

Attending doctorate program in Cellular Biochemistry at the Second University of Naples. Department of Biochemistry and Biophysics. 

2003-2004   

Post- doctoral  research fellow  at  the “Kimmel Cancer Center “of the  “ Thomas Jefferson University “,  Philadelphia, PA, in the labs  of Prof. Carlo Maria Croce. 

2004-2007 

Post-doctoral Researcher in Prof. Carlo Croce’ s labs, at the Dep. of Molecular Virology, Immunology and Medical Genetic of The Comprehensive Cancer Center, Ohio State University, Columbus, OH. 

AWARDS

2006-2008 American-Italian Cancer Foundation Fellowship for the project entitled: “MicroRNAs involvement in  Familiar CLL”at the Second University of Naples. Department of Biochemistry and Biophysics.

2009- 2011 

Fellowship by Fondazione Italiana per la Ricerca  sul Cancro (FIRC), with a project entitled: “Regulatory interaction between AP-1 and  microRNAs” at Dr. Verde’s Lab of Molecular Oncology,  Institute of Genetics and Biophysics (CNR, Naples)  

2011-2014 

GRANTS AWARDED: Ultraconserved Region Encoding ncRNAs involvement in Bladder tumors , Associazione Italiana per la Ricerca sul Cancro (AIRC).

28-10-2021

Start Cup Campania (2021) prize for translating basic research to enterprise for the project URiNBB- Urinary RNA Noncoding Bladder cancer Biomarker.