Nicola Zambrano
PhD
Born in 1963, laurea degree cum laude in Biological Sciences (1987) at the University of Naples, PhD in Biotechnology (1996), from 1996 to 2002 he is Assistant Professor in Biochemistry at the School of Medicine and Surgery, the University of Naples Federico II. Since 2002, he is Associate Professor then, from 2010, Full Professor of Molecular Biology. As a fellow of the Italian Association for Cancer Research, between 1989 and 1991, he worked on regulation of gene expression. From 1991 to 1994, at the National Cancer Institute in Bethesda, MD, USA, he was a visiting fellow, working on structure-function relationship of the p53 tumor suppressor protein, and on the HIVI nucleocapsid protein. Since 1994, at the Department of Biochemistry and Medical Biotechnologies, the University of Naples and at CEINGE Biotecnologie Avanzate, he participated to research projects leading to the identification of protein-protein interactions and signal transduction pathways, which contributed to the identification of various molecular complexes involving the Alzheimer's beta-amyloid precursor protein (APP) and the molecular adaptor, Fe65. Next, he studied the signaling mechanisms which regulate the proteolytic processing of APP, and its transcriptional effects, following the nuclear translocation of the Fe65/APP complex. He also generated and analyzed animal models for the functional study of the Fe65/APP system in the mouse and in the nematode Caenorhabditis elegans, through reverse genetics approaches. During 1997, he was visiting scientist at the European Molecular Biology Laboratory (Heidelberg, Germany), in the Gene Expression Programme. His most recent interests deal with the analysis of Carbonic anhydrase IX in patho-physiological conditions, and with Medical Biotechnologies.
He was responsible for Research Units of "national interest research projects", by Italian Authority of University and Research. He participated to Projects financed by EC within FP5, FP6 and FP7 Programmes. He is involved in editorial activities and routinely acts as a reviewer of scientific projects for national and international agencies and charities.
Carbonic anhydrase IX in pathophysiology of hypoxia
Among cellular stresses, hypoxia is largely recognized as a negative prognostic factor in cancer, since it contributes to metabolic alterations of tumor cells, chemo- and radio-resistance. Tumor cells indeed possess the ability to adapt to stress conditions. Carbonic anhydrase IX is a pivotal player in the protective responses to hypoxia. Using molecular and proteomic tools, our group is currently investigating the molecular mechanisms associated to cancer resistance to stress conditions. We recently characterized the interactome of carbonic anhydrase IX in hypoxic cells. We believe that the functional characterization of carbonic anhydrase IX and its molecular partners may highlight new scenarios in cancer biology, and clarify how tumor cells cope with hypoxic stresses. In fact, our most recent data highlight a mechanism, involving CA IX and its nuclear interactors, linked to attenuation of rRNA gene transcription during hypoxia. The latter may result a way, for the hypoxic cell, to adapt to the decreased nutrient availability, occurring during hypoxia. In the future, our results may provide innovative druggable targets for hypoxic tumors.
Improving screening procedures and production of biological therapeutics for preclinical uses
The fast-evolving field of cancer immunotherapy and related combination approaches represents a well-established paradigm for applications of biopharmaceuticals, such as monoclonal antibodies (mAbs) and oncolytic viruses. To overcome bottlenecks for their application, we implemented a screening-to-purification workflow, consisting in a platform for High Throughput Screening, based on next-generation sequencing, and in highly efficient production cell factories for both monoclonals and oncolytic vectors. To avoid classical screenings based on repeated, time-consuming binding assays, we identify potential binders of a given antigen evaluating the enrichments of binders within and between selection cycles. After in silico identification, the clones of interest are recovered from the enriched sublibraries and converted into full-length immunoglobulins.
Improving production of monoclonal antibodies and oncolytic viruses also represents an opportunity to facilitate target validations and preclinical studies. SINEUP RNAs are long non-coding transcripts, enhancing translation of target mRNAs. We implemented SINEUP technology co-expressing optimized SINEUPs and mRNAs of heavy and light chains, increasing up to three-fold the production of correctly assembled and glycosylated mAbs. We validated the whole platform for several targets, including those from a recently identified repertoire of immune checkpoint modulators, and thereby guarantee its wide potential in screening and production of biological therapeutics.
- Carbonic anhydrase IX in pathophysiology of hypoxia
- Improving screening procedures and production of biological therapeutics for preclinical uses
- Emanuele Sasso, Mariangela Succoio, PhD
- Guendalina Froechlich, Chiara Gentile, M.Sc.
- Sara Amiranda, Giovanna Evangelista, Arianna Finizio, Sarah Scatigna, B.Sc.
Rusciano G, Sasso E, Capaccio A, Zambrano N, Sasso A. Revealing membrane alteration in cells overexpressing CA IX and EGFR by Surface-Enhanced Raman Scattering. Sci Rep. 2019 Feb 12;9(1):1832.
Sasso E, Latino D, Froechlich G, Succoio M, Passariello M, De Lorenzo C, Nicosia A, Zambrano N. A long non-coding SINEUP RNA boosts semi-stable production of fully human monoclonal antibodies in HEK293E cells. MAbs. 2018 Jul;10(5):730-737.
Sasso E, Paciello R, D'Auria F, Riccio G, Froechlich G, Cortese R, Nicosia A, De Lorenzo C, Zambrano N.One-Step Recovery of scFv Clones from High-Throughput Sequencing-Based Screening of Phage Display Libraries Challenged to Cells Expressing Native Claudin-1. Biomed Res Int. 2015;2015:703213. doi: 10.1155/2015/703213.
Monteleone F, Rosa R, Vitale M, D'Ambrosio C, Succoio M, Formisano L, Nappi L, Romano MF, Scaloni A, Tortora G, Bianco R, Zambrano N. Increased anaerobic metabolism is a distinctive signature in a colorectal cancer cellular model of resistance to antiepidermal growth factor receptor antibody. Proteomics. 2013 Mar;13(5):866-77. doi: 10.1002/pmic.201200303.
Buanne P, Renzone G, Monteleone F, Vitale M, Monti SM, Sandomenico A, Garbi C, Montanaro D, Accardo M, Troncone G, Zatovicova M, Csaderova L, Supuran CT, Pastorekova S, Scaloni A, De Simone G, Zambrano N Characterization of carbonic anhydrase IX interactome reveals proteins assisting its nuclear localization in hypoxic cells. J Proteome Res. 2013 Jan 4;12(1):282-92.