The Unit of Molecular and Computational Biology combines molecular and cellular biology techniques to computational tools and next-generation sequencing technologies in the context of cancer and metabolic diseases. The research efforts are devoted to:

Targeting long non-coding RNAs and metabolism in cancer.

The main research interest is to identify new therapeutic strategies for BRAF-driven thyroid carcinomas based on the targeting of tumor-specific long non-coding RNAs and of tumor metabolic vulnerabilities.

This research line, currently focused on papillary and anaplastic thyroid carcinomas, aims 1) to functionally characterize tumor-associated lncRNAs, evaluate, in vitro and in vivo, their oncogenic potential and to evaluate their targeting as co-adjuvant of drug-based therapies; 2) to explore metabolic reprogramming of tumor cells as Achille’s heel to improve the effectiveness of available targeted therapies.

Dissecting the contribution of PPARG isoforms to adipose tissue pathophysiology.

The research interest is to define if, and how, alterations in the splicing pattern of the transcription factor PPARG in adipose tissue contribute to human metabolic disorders. This research line combines functional approaches in cell models (adipose tissue-derived mesenchymal stem cells and mature adipocytes) to advanced (NGS) and standard molecular techniques on human samples, and aims 1) to explore the role of PPARG dominant negative isoforms in adipocyte biology, from their commitment to terminal differentiation; 2) to evaluate the functional relevance of these isoforms in pathological conditions such as hypertrophic obesity and type 2 diabetes.

Targeting long non-coding RNAs and metabolism in cancer.

• Aprile M, Costa V, Cimmino A, Calin GA. Emerging role of oncogenic long non-coding RNA as cancer biomarkers. Int J Cancer. 2022 Sep 8. doi: 10.1002/ijc.34282. Epub ahead of print. PMID: 36082440.
• Federico A, Fratello M, Scala G, Möbus L, Pavel A, Del Giudice G, Ceccarelli M, Costa V, Ciccodicola A, Fortino V, Serra A, Greco D. Integrated Network Pharmacology Approach for Drug Combination Discovery: A Multi-Cancer Case Study. Cancers (Basel). 2022 Apr 18;14(8):2043. doi: 10.3390/cancers14082043. PMID: 35454948; PMCID: PMC9028433.
• 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. PMID: 33567603.
• Aprile M, Katopodi V, Leucci E, Costa V. LncRNAs in Cancer: From garbage to Junk. Cancers (Basel). 2020 Oct 31;12(11):E3220. PMID: 33142861.
• Cave DD, Di Guida M, Costa V, Sevillano M, Ferrante L, Heeschen C, Corona M, Cucciardi A, Lonardo E. TGF-β1 secreted by pancreatic stellate cells promotes stemness and tumourigenicity in pancreatic cancer cells through L1CAM downregulation. Oncogene. 2020 Apr 14.
• Malapelle U, Pepe F, Pisapia P, Sgariglia R, Nacchio M, De Luca C, Lacalamita R, Tommasi S, Pinto R, Palomba G, Palmieri G, Vacirca D, Barberis M, Bottillo I, Grammatico P, Grillo LR, Costa V, Smeraglio R, Bruzzese D, Troncone G. Harmonization of Next-Generation Sequencing Procedure in Italian Laboratories: A Multi-Institutional Evaluation of the SiRe® Panel. Front Oncol. 2020 Mar 11;10:236. doi: 10.3389/fonc.2020.00236. PMID: 32219061; PMCID: PMC7078327.
• Esposito R, Esposito D, Pallante P, Fusco A, Ciccodicola A, Costa V. Oncogenic Properties of the Antisense lncRNA COMET in BRAF- and RET-Driven Papillary Thyroid Carcinomas. Cancer Research. 2019 May 1;79(9):2124-2135.
• Ambrosio MR, D'Esposito V, Costa V, Liguoro D, Collina F, Cantile M, Prevete N, Passaro C, Mosca G, De Laurentiis M, Di Bonito M, Botti G, Franco R, Beguinot F, Ciccodicola A, Formisano P. Glucose impairs tamoxifen responsiveness modulating Connective Tissue Growth Factor in breast cancer cells. Oncotarget 2017 Nov 20;8(65):109000-109017.
• Terracciano D, Terreri S, de Nigris F, Costa V, Calin GA, Cimmino A. The role of a new class of long non-coding RNAs transcribed from ultraconserved regions in cancer. BBA Rev Cancer 2017 Sep 12. pii: S0304-419X(17)30110-5. doi: 10.1016/j.bbcan.2017.09.001.
• Federico A, Rienzo M, Abbondanza C, Costa V, Ciccodicola A, Casamassimi A. Pan-Cancer Mutational and Transcriptional Analysis of the Integrator Complex. Int J Mol Sci. 2017 Apr 29;18(5).
• Petrizzo A, Caruso FP, Tagliamonte M, Tornesello ML, Ceccarelli M, Costa V, Aprile M, Esposito R, Ciliberto G, Buonaguro FM, Buonaguro L. Identification and Validation of HCC-specific Gene Transcriptional Signature for Tumor Antigen Discovery. Scientific Reports. 2016 Jul 8;6:29258.
• Costa V, Esposito R, Pallante P, Ciccodicola A and Fusco. The "next-generation" knowledge of papillary thyroid carcinoma. Cell Cycle, 2015 Jun 1:0.
• Costa V, Esposito R, Ziviello C, Sepe R, Bim LV, Cacciola NA, Decaussin-Petrucci M, Pallante P, Fusco A and Ciccodicola. New somatic mutations and WNK1-B4GALNT3 gene fusion in papillary thyroid carcinoma. Oncotarget. 2015 Mar 14.

Dissecting the contribution of PPARG isoforms to adipose tissue pathophysiology

• Cataldi S, Aprile M, Melillo D, Mucel I, Giorgetti-Peraldi S, Cormont M, Italiani P, Blüher M, Tanti JF, Ciccodicola A, Costa V*. TNFα Mediates Inflammation-Induced Effects on PPARG Splicing in Adipose Tissue and Mesenchymal Precursor Cells. Cells 2021 Dec 24;11(1):42. doi: 10.3390/cells11010042.
• Cataldi, S., Costa, V., Ciccodicola, A., and Aprile, M. (2021). PPARγ and Diabetes: Beyond the Genome and Towards Personalized Medicine. Current diabetes reports, 21(6), 18.
• Aprile M, Cataldi S, Perfetto C, Ambrosio MR, Italiani P, Tatè R, Blüher M, Ciccodicola A, Costa V*. (2020). In Vitro-Generated Hypertrophic-Like Adipocytes Displaying PPARG Isoforms Unbalance Recapitulate Adipocyte Dysfunctions In Vivo. Cells, 9(5), E1284.
• Aprile M, Cataldi S, Ambrosio MR, D'Esposito V, Lim K, Dietrich A, Blüher M, Savage DB, Formisano P, Ciccodicola A, Costa V*. PPARγΔ5, a Naturally Occurring Dominant-Negative Splice Isoform, Impairs PPARγ Function and Adipocyte Differentiation. Cell Reports. 2018 Nov 6;25(6):1577-1592.e6.
• Parrillo L, Costa V, Raciti G, Longo M, Spinelli R, Esposito R, Nigro C, Vastolo V, Desiderio A, Zatterale F, Ciccodicola A, Formisano P, Miele C, and Beguinot F. Hoxa5 undergoes dynamic DNA methylation and transcriptional repression in the adipose tissue of mice exposed to high-fat diet. Int J Obesity (Lond). 2016, Mar 16.
• Pollastro C, Ziviello C, Costa V and Ciccodicola A. Pharmacogenomics of Drug Response in Type 2 Diabetes: Toward the Definition of Tailored Therapies? PPAR Research.
• Aprile M, Ambrosio MR, D'Esposito V, Beguinot F, Formisano P, Costa V* and Ciccodicola A. PPARG in human adipogenesis: differential contribution of canonical transcripts and dominant negative isoforms. PPAR Res. 2014.
• Costa V, Ciccodicola A. Is PPARG the key gene in diabetic retinopathy? Br J Pharmacol. 2012 Jan; 165(1):1-3. doi: 10.1111/j.1476-5381.2011.01443.x. PubMed PMID: 21501146; PubMed Central PMCID: PMC3252961. 
• Costa V, Gallo MA, Letizia F, Aprile M, Casamassimi A, Ciccodicola A. PPARG: Gene Expression Regulation and Next-Generation Sequencing for Unsolved Issues. PPAR Res. 2010;2010. pii: 409168. doi: 10.1155/2010/409168. Epub 2010 Sep 8. 
• Costa V, Casamassimi A, Esposito K, Villani A, Capone M, Iannella R, Schisano B, Ciotola M, Di Palo C, Corrado FC, Santangelo F, Giugliano D, Ciccodicola A. Characterization of a novel polymorphism in PPARG regulatory region associated with type 2 diabetes and diabetic retinopathy in Italy. J Biomed Biotechnol. 2009; 2009:126917. doi: 10.1155/2009/126917. Epub 2008 Dec 25. PubMed PMID: 19125195; PubMed Central PMCID: PMC2610251. 

Education

• December 2008. PhD in Metabolism and Ageing - Faculty of Medicine, University of Campania Luigi Vanvitelli.
• March 2005. MSc in Biotechnology - Federico II University of Naples.

Research and teaching

• April 2015 - present. CNR Researcher, IGB-CNR Naples.
• June 2014 - March 2015. CNR Researcher (temporary position), IGB-CNR Naples.
• June 2013 - May 2014. Senior PostDoc fellow, IGB-CNR.
• June 2012 - May 2013. Junior PostDoc fellow, DiSMET, "Federico II" University of Naples.
• 2011-present. Teaching Assistant in Molecular Biology, “Parthenope” University.
• January 2009 - May 2012. Junior PostDoc fellow, IGB-CNR.
• 2009-2019. Teaching Assistant in Genetics, “Parthenope” University of Naples.

Awards and Honors

• Qualified as Associate Professor in Molecular Biology (valid until 2029)
• Qualified as Associate Professor in General and Clinical Pathology (valid until 2029)
• Member of the IGB-CNR International Workshop Organizing Committee
• Winner of International Scientific Award "Nunzio Pascale" (XXI Edition), October 2016
• Editorial Board Member, Hereditas
• Associate Editor, Frontiers in Genetics, section Cancer Genetics and Oncogenomics
• Review Editor, Frontiers in Genetics, section Applied Genetic Epidemiology
• Topic Editor, Cancers
• Editorial Board Member, Journal of Human Transcriptome (past position)

Current research grants (funded as PI or as member of research unit)

• 2020-2025. MFAG (My First AIRC Grant) "Assessing COMET Silencing as new Therapeutic Option in Braf-Mutated Thyroid Carcinomas". PI of the Project.
• 2019-2021. PON "Innovative Devices For SHAping the RIsk of Diabetes (IDF SHARID)". Member of IGB-CNR Unit.
• 2018-2020. POR Campania FESR 2014/2020 "Sviluppo di Approcci Terapeutici INnovativi per patologie neoplastiche resistenti ai trattamenti (SATIN)". Member of IGB-CNR Unit.