WELCOME TO THE LAGANÀ LAB

RESEARCH

Computational Cancer Genomics and Precision Oncology

Our team focuses on the development and application of computational tools for integrative analysis of multi-omics data to investigate the role of coding and non-coding alterations on cancer pathogenesis and progression, understand clinical implications of tumor clonal heterogeneity, inform patient risk stratification, and develop personalized therapy selection approaches guided by network genomics.

ALESSANDRO LAGANÀ, PHD

Principal Investigator

Alessandro Laganà is an Assistant Professor of Oncological Sciences and Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai.  His research interests lie primarily in the area of integrative cancer genomics, cancer network biology and precision oncology, with particular focus on Multiple Myeloma, a malignancy of bone marrow plasma cells.

Alessandro achieved his MS degree in Computer Science and PhD in Biology, Human Genetics and Bioinformatics at the University of Catania (Italy), under the supervision of Alfredo Ferro, and completed his Post-Doctoral studies in Carlo Croce's Lab at The Ohio State University in Columbus, OH, where his 

research focused primarily on microRNA.

SHERRY BHALLA, PHD

Post-doctoral Researcher (co-mentored with Samir Parekh)

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WALEED OSMAN

Data Engineer

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PAULA RESTREPO

Associate Researcher II

Paula's projects focus on personalized cancer genomics, drug resistance, and intratumoral heterogeneity in multiple myeloma. In her spare time, she enjoys watercolor painting and playing with her two cats.

MEGHANA RAM

Associate Researcher II

Meghana received her master’s degree in Individualized Genomics and Health from Johns Hopkins University. She plans to pursue a PhD. in the future, with an intent to have a career in academia. In her spare time, she enjoys reading, cooking, dancing Kathak (Indian classical dance form) and learning new languages.

DAVID MELNEKOFF

PhD Student (co-mentored with Samir Parekh)

David is focusing on precision cancer medicine and clinical decision making based on genomic sequencing. He received his B.S. from Columbia University in Biochemistry, and his M.S. from the Icahn School of Medicine prior to his matriculation into the PhD program in 2018. David’s research focus is the study and implementation of Intra-Tumor Heterogeneity estimates as it relates to patient treatment and outcomes, with a special focus on novel immune therapeutics including Chimeric Antigen T Cell (CAR T) and Bi-specific Antibody treatments. David will use computational methods to elucidate the mechanisms of resistance to these new therapies, with the hopes of providing alternative and complimentary drug recommendations for a challenging patient cohort. David also has an interest in emerging genomic sequencing technology, specifically multi-omic single-cell sequencing modalities.

OLIVER VAN OEKELEN

PhD Student (co-mentored with Samir Parekh)

Oliver is a medical doctor, trained in bioinformatics, with a degree from the University of Leuven (KU Leuven) in Belgium. He has completed the first two years of residency in Belgium, after which he joined the PhD in Biomedical Sciences program at the Icahn School of Medicine at Mount Sinai in 2018. His research focuses on the immune repertoire in patients with multiple myeloma in the context of novel immune therapies (e.g. chimeric antigen receptor (CAR) T cells, monoclonal antibodies and novel immunomodulatory agents (IMiDs)). Using next generation sequencing at the single-cell level and high-dimensional phenotyping (mass cytometry), Oliver hopes to clarify the intricate crosstalk between various cell types in the bone marrow microenvironment. Oliver has a broad interest in transitional biomedical research in immunology and oncology with a focus on bioinformatics and medical informatics.

PEER-REVIEWED PUBLICATIONS

• O. Van Oekelen, A. Aleman, B. Upadhyaya, S. Schnakenberg, D. Madduri, S. Gavane, J. Teruya-Feldstein, J. F. Crary, M. E. Fowkes, C. B. Stacy, S. Kim-Schulze, A. Rahman, A. Laganà, J. D. Brody, M. Merad, S. Jagannath, S. Parekh. Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy. Nature Medicine 2021; https://doi.org/10.1038/s41591-021-01564-7.
  
  

• S. Bhalla, D. T. Melnekoff, A. Aleman, V. Leshchenko, P. Restrepo, J. Keats, K. Onel, J. R. Sawyer, D. Madduri, J. Richter, S. Richard, A. Chari, H. J. Cho, J. T. Dudley, S. Jagannath, A. Laganà, S. Parekh. Patient Similarity Network of Multiple Myeloma identifies patient sub-groups with distinct genetic and clinical features. Science Advances 2021; 7(47). doi:10.1126/sciadv.abg9551.

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• S. S. Jatiani, S. Christie, V. V. Leshchenko, R. Jain, A. Kapoor, P. Bisignano, C. Lee, H. Ü. Kaniskan, D. Edwards, F. Meng, A. Laganà, Y. Youssef, A. Wiestner, L. Alinari, J. Jin, M. Filizola, A. K. Aggarwal, S. Parekh. SOX11 Inhibitors Are Cytotoxic in Mantle Cell Lymphoma. Clin Cancer Res 2021; 27(16):4652-4663. doi: 10.1158/1078-0432.CCR-20-5039.

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• G. P. Marceca, R. Distefano, L. Tomasello, A. Laganà, F. Russo, F. Calore, G. Romano, M. Bagnoli, P. Gasparini, A. Ferro, M. Acunzo, Q. Ma, C. M. Croce, G. Nigita. MiREDiBase, a manually curated database of validated and putative editing events in microRNAs. Scientific Data 2021; 8:199. doi: https://doi.org/10.1038/s41597-021-00979-8

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• A. Chari, E. Florendo, I. S. Mancia, H. Cho, D. Madduri, S. Parekh, J. Richter, A. Dhadwal, J. Thomas, G. Jiang, A. Laganà, S. Bhalla, S. Jagannath. Optimal Supportive Care with Selinexor Improves Outcomes in Patients with Relapsed/Refractory Multiple Myeloma. Clinical Lymphoma, Myeloma & Leukemia 2021; doi: https://doi.org/10.1016/j.clml.2021.07.014.

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• R. Upadhyay, J. A. Boiarsky, G. Pantsulaia, J. Svensson-Arvelund, M. J. Lin, A. Wroblewska, S. Bhalla, N. Scholler, A. Bot, J. M. Rossi, N. Sadek, S. Parekh, A. Laganà, A. Baccarini, M. Merad, B. D. Brown, J. D. Brody. A critical role for fas-mediated off-target tumor killing in T cell immunotherapy. Cancer Discovery 2020; doi: 10.1158/2159-8290.CD-20-0756.

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• M. R. Sapienza, F. Fuligni, F. Melle, V. Tabanelli, V. Indio, M. A. Laginestra, G. Motta, S. Mazzara, L. Cerroni, A. Pileri, F. Facchetti, M. Paulli, L. Cascione, A. Laganà, E. Berti, C. Agostinelli, E. Sabattini, C. M. Croce, S. A. Pileri. MicroRNA profiling of Blastic Plasmacytoid Dendritic Cell Neoplasm and Myeloid Sarcoma. Hematological Oncology 2020; doi: https://doi.org/10.1002/hon.2782.

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• O. Van Oekelen, S. Parekh, H. J. Cho, N. Vishnuvardhan, D. Madduri, J. Richter, C. Ip, K. Lau, E. Florendo, I. S. Mancia, J. Thomas, D. Verina, E. Chan, K. Zarychta, L. La, G. Strumolo, D. T. Melnekoff, V. V. Leshchenko, S. Kim-Schulze, S. Cuoto, M. Wang, W. E. Pierceall, A. Thakurta, A. Laganà, S. Jagannath, A. Chari. A Phase II Study of Pomalidomide, Daily Oral Cyclophosphamide, and Dexamethasone in Relapsed/Refractory Multiple Myeloma. Leukemia & Lymphoma 2020; doi: 10.1080/10428194.2020.1805111.

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• A. Ma, E. Stratikopoulos, K.S. Park, J. Wei, T. C. Martin, X. Yang, M. Schwarz, V. Leshchenko, A. Rialdi, B. Dale, A. Laganà, E. Guccione, S. Parekh, R. Parsons, J. Jin. Discovery of a first-in-class EZH2 selective degrader. Nature Chemical Biology 2020; 16(2):214-222. doi: 10.1038/s41589-019-0421-4.

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• D. Perumal, N. Imai, A. Laganà, J. P. Finnigan, D. T. Melnekoff, V. Leshchenko, A. Solovyov, D. Madduri, S. Kim-Schulze, A. Chari, H. J. Cho, J. T. Dudley, J. Brody, B. Barlogie, S. Jagannath, B. Greenbaum, S. Gnjatic, N. Bhardwaj, S. Parekh. Patient-Specific Mutation-Derived Tumor Antigens as Targets for Cancer Immunotherapy in Multiple Myeloma. Clinical Cancer Research 2020; 15;26(2):450-464. doi: 10.1158/1078-0432.CCR-19-2309.

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• Y. Liu, H. Yu, S. Yoo, E. Lee, A. Laganà, S. Parekh, E. E. Schadt, L. Wang, J. Zhu. A Network Analysis of Multiple Myeloma Related Gene Signatures. Cancers (Basel) 2019; 11(10). pii: E1452. doi: 10.3390/cancers11101452.

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• A. Laganà, I. Beno, D. Melnekoff, V. Leshchenko, D. Madduri, D. Ramdas, L. Sanchez, S. Niglio, D. Perumal, B. A. Kidd, R. Miotto, J. Houldsworth, R. Shaknovich, A. Chari, H. J. Cho, B. Barlogie, S. Jagannath, J. T. Dudley, S. Parekh. Precision Medicine for Relapsed Multiple Myeloma on the Basis of an Integrative Multiomics Approach. JCO Precision Oncology  2018. doi: 10.1200/PO.18.00019.

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• L. Shi, J. Middleton, Y. J. Jeon, P. Magee, D. Veneziano, A. Laganà, H. S. Leong, S. Sahoo, M. Fassan, R. Booton, R. Shah, P. A. J. Crosbie, M. Garofalo. KRAS induces lung tumorigenesis through microRNAs modulation. Cell Death Dis 2018; 13;9(2):219. doi: 10.1038/s41419-017-0243-9.

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• S. Naidu, L. Shi, P. Magee, J. D. Middleton, A. Laganà, S. Sahoo, H. S. Leong, M. Galvin, K. Frese, C. Dive, V. Guzzardo, M. Fassan, M. Garofalo. PDGFR-modulated miR-23b cluster and miR-125a-5p suppress lung tumorigenesis by targeting multiple components of KRAS and NF-kB pathways. Scientific Reports 2017; doi:10.1038/s41598-017-14843-6.

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• F. Russo, S. Di Bella, F. Vannini, G. Berti, F. Scoyni, H. V. Cook, A. Santos, G. Nigita, V. Bonnici, A. Laganà, F. Geraci, A. Pulvirenti, R. Giugno, F. De Masi, K. Belling, L. J. Jensen, S. Brunak, M. Pellegrini, A. Ferro. miRandola 2017: a curated knowledge base of non-invasive biomarkers. Nucleic Acids Res 2017; gkx854, https://doi.org/10.1093/nar/gkx854.

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• A. Chari, H. J. Cho, A. Dhadwal, G. Morgan, L. La, K. Zarychta, D. Catamero, E. Florendo, N. Stevens, D. Verina, E. Chan, V. Leshchenko, A. Laganà, D. Perumal, A. H. Mei, K. Tung, J. Fukui, S. Jagannath, S. Parekh. A phase 2 study of panobinostat with lenalidomide and weekly dexamethasone in myeloma. Blood Advances 2017; doi:10.1182/bloodadvances.2017007427.

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• A. Laganà, W. P. Dirksen, W. Supsavhad, A. S. Yilmaz, H. G. Ozer, J. D. Feller, K. A. Vala, C. M. Croce, T. J. Rosol. Discovery and characterization of the feline miRNAome. Scientific Reports 2017; doi:10.1038/s41598-017-10164-w.

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• A. Laganà, D. Perumal, D. Melnekoff, B. Readhead, B. A. Kidd, V. Leshchenko, P.-Y. Kuo, J. Keats, M. DeRome, J. Yesil, D. Auclair, S. Lonial, A. Chari, H. J. Cho, B. Barlogie, S. Jagannath, J. T. Dudley, S. Parekh. Integrative network analysis identifies novel drivers of pathogenesis and progression in newly diagnosed multiple myeloma. Leukemia 2017; doi: 10.1038/leu.2017.197.

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• M. Acunzo, G. Romano, G. Nigita, D. Veneziano, L. Fattore, A. Laganà, N. Zanesi, P. Fadda, M. Fassan, L. Rizzotto, R. Kladney, V. Coppola, C. M. Croce. Selective targeting of point-mutated KRAS through artificial microRNAs. Proc Natl Acad Sci U S A 2017; doi: 10.1073/pnas.1620562114.

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• D. Veneziano, S. Di Bella, G. Nigita, A. Laganà, A. Ferro, C. M. Croce. Non-coding RNA: Current Deep Sequencing Data Analysis Approaches and Challenges. Human Mutation 2016; 37 (12) 1283-1298.

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• L. Fattore, R. Mancini, M. Acunzo, G. Romano, A. Laganà, M. E. Pisanue, D. Malpiccie, G. Madonna, D. Mallardo, M. Capone, F. Fulciniti, L. Mazzucchelli, G. Botti, C. M. Croce, P. A. Ascierto, G. Ciliberto. miR-579-3p controls melanoma progression and resistance to target therapy. Proc Natl Acad Sci U S A 2016; 113(34):E5005-13. doi: 10.1073/pnas.1607753113.

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• G. Nigita, M. Acunzo, G. Romano, D. Veneziano, A. Laganà, M. Vitiello, D. Wernicke, A. Ferro, C. M. Croce. microRNA editing in seed region aligns with cellular changes in hypoxic conditions. Nucleic Acids Res 2016; doi: 10.1093/nar/gkw532.

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• A. Laganà, D. Veneziano, T. Spata, R. Tang, H. Zhu, P. J. Mohler, A. Kilic. Identification of General and Heart-Specific miRNAs in Sheep (Ovis aries). PLOS ONE 2015; doi: 10.1371/jour- nal.pone.0143313.

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• A. Laganà, A. Ferro, C. M. Croce. Editorial: Bioinformatics of Non-Coding RNAs with Applications to Biomedicine: Recent Advances and Open Challenges. Front. Bioeng. Biotechnol. 2015; 3:156. doi: 10.3389/fbioe.2015.00156.

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• E. Tili, M. Chiabai, D. Palmieri, M. Brown, R. Cui, C. Fernandes, T. Richmond, T. Kim, T. Sheetz, H. L. Sun, A. Laganà, D. Veneziano, S. Volinia, L. Rassenti, T. Kipps, H. Awad, J. J. Michaille, C. M. Croce. Quaking and miR-155 interactions in inflammation and leukemogenesis. Oncotarget 2015.

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• P. Joshi P, Y. J. Jeon, A. Laganà, J. Middleton, P. Secchiero, M. Garofalo, C. M. Croce. MicroRNA- 148a reduces tumorigenesis and increases TRAIL-induced apoptosis in NSCLC. Proc Natl Acad Sci U S A 2015; 112(28):8650-5.

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• Y. J. Jeon, J. Middleton, T. Kim, A. Laganà, C. Piovan, P. Secchiero, G. J. Nuovo, R. Cui, P. Joshi, G. Romano, G. Di Leva, B. K. Lee, H. L. Sun, Y. Kim, P. Fadda, H. Alder, M. Garofalo, C. M. Croce. A set of NF-kB-regulated microRNAs induces acquired TRAIL resistance in Lung cancer. Proc Natl Acad Sci U S A 2015; 112(26):E3355-64.

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• A. Drusco, A. Bottoni, A. Laganà, M. Acunzo, M. Fassan, L. Cascione, A. Antenucci, P. Kumchala, C. Vicentini, M. P. Gardinam, H. Alder, M. A. Carosi, M. Ammirati, S. Gherardi, M. Luscrì, C. Carapella, N. Zanesi, C. M. Croce. A differentially expressed set of micrornas in cerebro-spinal fluid (CSF) can diagnose CNS malignancies. Oncotarget 2015.

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• C. Tibaldi, A. D’Incecco, A. Laganà. MicroRNAs and Targeted Therapies in Non-Small Cell Lung Cancer: Minireview. Anticancer Agents Med Chem 2015.

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• A. Laganà, D. Shasha, C. M. Croce. Synthetic RNAs for gene regulation: design principles and computational tools. Front Bioeng Biotechnol 2014; 2:65. doi: 10.3389/fbioe.2014.00065.

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• S. V. Thomas, A. Laganà, K. M. Dittmar, P. E. Wakely Jr. Imprint cytopathology of core needle biopsies: a first responder role for cytotechnologists. Journal of the American Society of Cytopathology 2014; 4(1): 16-24.

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• A. Efanov, N. Zanesi, V. Coppola, G. Nuovo, B. Bolon, D. Wernicke-Jameson, A. Laganà, H. Alder, F. Pichiorri and C. M. Croce. Human HMGA2 protein overexpressed in mice induces precursor T-cell lymphoblastic leukemia. Blood Cancer J 2014; 4:e227.

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• F. Russo, S. Di Bella, V. Bonnici, A. Laganà, G. Rainaldi, M. Pellegrini, A. Pulvirenti, R. Giugno, A. Ferro. A knowledge base for the discovery of function, diagnostic potential and drug effects on cellular and extracellular miRNAs. BMC Genomics 2014; 15(Suppl 3):S4.

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• A. Laganà, M. Acunzo, G. Romano, A. Pulvirenti, D. Veneziano, L. Cascione, R. Giugno, P. Gasparini, D. Shasha, A. Ferro, C. M. Croce. miR-Synth: a computational resource for the design of multi-site multi-target synthetic miRNAs. Nucleic Acids Res 2014; doi:10.1093/nar/gku202.

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• P. Nasarre, R. M. Gemmill, V. A. Potiron, J. Roche, X. Lu, A. E. Baron, C. Korch, E. Garrett-Mayer, A. Laganà, P. H. Howe, H. A. Drabkin. Neuropilin-2 is upregulated in lung cancer cells during TGF1-induced epithelialmesenchymal transition. Cancer Res 2013; 73(23):7111-7121.

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• A. Laganà, F. Russo, D. Veneziano, S. Di Bella, A. Pulvirenti, R. Giugno, C. M. Croce, A. Ferro. Extracellular circulating viral microRNAs: current knowledge and perspectives. Frontiers in Genetics 2013; 4:120.

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• M. Acunzo, G. Romano, D. Palmieri, A. Laganà, M. Garofalo, V. Balatti, A. Drusco, M. Chiariello, P. Nana-Sinkam, C. M. Croce. Cross-talk between MET and EGFR in non-small cell lung cancer involves miR-27a and Sprouty2. Proc Natl Acad Sci U S A 2013; 110(21):8573-8578.

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• F. Pichiorri, D. Palmieri, L. De Luca, J. Consiglio, J. You, A. Rocci, T. Talabere, C. Piovan, A. Laganà, L. Cascione, J. Guan, P. Gasparini, V. Balatti, G. Nuovo, V. Coppola, C. C. Hofmeister, G. Marcucci, J. C. Byrd, S. Volinia, C. L. Shapiro, M. A. Freitas, C. M. Croce. In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation. J Exp Med 2013; 210(5):951-68.

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• N. Zanesi, V. Balatti, J. Riordan, A. Burch, L. Rizzotto, A. Palamarchuk, L. Cascione, A. Laganà, A. J. Dupuy, C. M. Croce, Y. Pekarsky. A Sleeping Beauty screen reveals NF-kB activation in CLL mouse model. Blood 2013; 121(21):4355-4358.

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• V. Manfè, E. Biskup, A. Willumsgaard, A. G. Skov, D. Palmieri, P. Gasparini, A. Laganà, A. Woet- mann, N. Odum, C. M. Croce, R. Gniadecki. cMyc/miR-125b-5p Signalling Determines Sensitivity to Bortezomib in Preclinical Model of Cutaneous T-Cell Lymphomas. PLoS ONE 2013; 8(3): e59390.

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• R. Distefano, G. Nigita, V. Macca, A. Laganà, R. Giugno, A. Pulvirenti, A. Ferro. VIRGO: visualization of A-to-I RNA editing sites in genomic sequences. BMC Bioinformatics 2013; 14(Suppl 7): S5.

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• F. Russo, S. Di Bella, G. Nigita, V. Macca, A. Laganà, R. Giugno, A. Pulvirenti, A. Ferro. miRandola: Extracellular Circulating MicroRNAs Database. PLoS ONE 2012; 7(10): e47786.

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• A. Laganà, A. Paone, D. Veneziano, L. Cascione, P. Gasparini, S. Carasi, F. Russo, G. Nigita, V. Macca, R. Giugno, A. Pulvirenti, D. Shasha, A. Ferro, C. M. Croce. miR-EdiTar: A database of predicted A-to-I edited miRNA target sites. Bioinformatics 2012; 28(23): 3166-3168.

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• P. Ranganathan, C. E. Heaphy, S. Costinean, N. Stauffer, C. Na, M. Hamadani, R. Santhanam, C. Mao, P. A. Taylor, S. Sandhu, G. He, A. Shana’ah, G. J. Nuovo, A. Laganà, L. Cascione, S. Obad, O. Broom, S. Kauppinen, J. C. Byrd, M. Caligiuri, D. Perrotti, G. A. Hadley, G. Marcucci, S. M. Devine, B. R. Blazar, C. M. Croce, R. Garzon. Regulation of acute graft-versus-host disease by microRNA-155. Blood 2012; 119(20): 4786-4797.

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• A. Laganà, F. Russo, C. Sismeiro, R. Giugno, A. Pulvirenti, A. Ferro. Variability in the Incidence of miRNAs and Genes in Fragile Sites and the Role of Repeats and CpG Islands in the Distribution of Genetic Material. PLoS ONE 2010; 5(6): e11166.

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• A. Laganà, S. Forte, F. Russo, R. Giugno, A. Pulvirenti, A. Ferro. Prediction of human targets for viral-encoded microRNAs by thermodynamics and empirical constraints. Journal of RNAi and Gene Silencing 2010; 6(1): 379-385.

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• A. Laganà, S. Forte, A. Giudice, M. R. Arena, P. L. Puglisi, R. Giugno, A. Pulvirenti, D. Shasha, A. Ferro. miRò: a miRNA knowledge base. Database 2009; Vol. 2009, bap008.

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• V. Svicher, C. Alteri, R. DArrigo, A. Laganà, M. Trignetti, S. Lo Caputo, A. P. Callegaro, F. Maggiolo, F. Mazzotta, A. Ferro, S. Dimonte, S. Aquaro, G. di Perri, S. Bonora, C. Tommasi, M. P. Trotta, P. Narciso, A. Antinori, C. F. Perno, F. Ceccherini-Silberstein. The Treatment with the Fusion Inhibitor Enfuvirtide Influences the Appearance of Mutations in the HIV-1 Regulatory Protein Rev. Antimicrobial Agents and Chemotherapy 2009; 53(7): 2816-2823.

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• C. Di Pietro, M. Ragusa, D. Barbagallo, L. R. Duro, M. R. Guglielmino, A. Majorana V. Giunta, A. Rapisarda, E. Tricarichi, M. Miceli, R. Angelica, A. Grillo, B. Banelli, I. Defferari, S. Forte, A. Laganà, C. Bosco, R. Giugno, A. Pulvirenti, A. Ferro, K. H. Grzeschik, A. Di Cataldo,G. P. Tonini, M. Romani, M. Purrello. Involvement of GTA protein NC2beta in Neuroblastoma pathogenesis suggests that it physiologically participates in the regulation of cell proliferation. Molecular Cancer 2008; 7:52.

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• C. Di Pietro, M. Ragusa, L. Duro, M. R. Guglielmino, D. Barbagallo, A. Carnemolla, A. Laganà, P. Buffa, R. Angelica, A. Rinaldi, M. S. Calafato, I. Milicia, C. Caserta, R. Giugno, A. Pulvirenti, V. Giunta, A. Rapisarda, V. Di Pietro, A. Grillo, A. Messina, A. Ferro, K. H. Grzeschik, M. Purrello. Genomics, Evolution and Expression of TBPL2, a Member of the TBP Family. DNA and Cell Biology 2007; 26(6): 369-385.

CONTACT US

Icahn School of Medicine at Mount Sinai

Department of Oncological Sciences

Department of Genetics and Genomic Sciences

Tisch Cancer Institute

1470 Madison Avenue New York NY 10029

alessandro.lagana@mssm.edu