Morpho-functional organization and regulation of the biosynthetic pathway lab
Keywords: Golgi complex; Secretory pathway; Control systems; Glycosylation; Trafficking
Group leader: Alberto Luini (Associate Researcher)
Contacts
Phone: +39 0816132722
Lab: +39 0816132645
Email: a.luini@ieos.cnr.it
alberto.luini@cnr.it
PAST AND CURRENT INTERESTS AND ACTIVITIES
After graduating in Medicine in Milan, I worked in Italy and then in Israel and the United States with the Nobel laureate J. Axelrod for many years on drug metabolism, neuropharmacology and signal transduction. Since my return to Italy I dedicated myself to the study of intracellular transport apparatus and to the development of imaging technologies necessary for the studies on membrane transport. I now have a laboratory at the IEOS CNR in Naples and work in close collaboration with group leaders with similar interests in the same Institute.
CURRENT INTERESTS AND RELATED ACHIEVEMENTS
Mechanism of protein/lipid transport and processing by glycosylation in the Golgi complex. We were the first to demonstrate the maturation of cellular compartments such as the Golgi and the endosomes (Cell, 1998), which is a major mechanism of intracellular transport. This discovery provides the basis for understanding the glycosylation process in the Golgi complex (the cellular "glycosylation factory").
Mechanism of action and pharmacology of the Golgi-based oncogene Golph3 and other glyco-oncogenes. Based on the above work, we analyzed the mechanism of action of Golph3, an oncogene located in the Golgi complex, and discovered that it acts through the cisternal maturation mechanism, by accelerating the retrograde transport of a group of enzymes involved in the synthesis of glycosphingolipids.
Auto-regulatory systems of the intracellular transport apparatus as part of the overall regulatory map
We have discovered and described in a series of studies several autoregulatory, or control, systems of the transport apparatus (Nature, 1993, Nature Cell Biol, 2008, Cell, 2018)). These systems are fundamental in the physiology and pathology of the intracellular transport apparatus and of the whole cell.
Imaging technology and correlative light-electron microscopy (CLEM)
We developed the correlative light-electron microscopy (CLEM) technique for the study of the membrane transport. CLEM is today used widely and has given rise to a series of other correlative microscopic techniques, also widely used. This led to my election by EMBL first coordinator of ELMI (European Light Microscopy Initiative), the scientific society that later gave rise to the European Eurobioimaging infrastructure.
MAIN HONORS AND BOARDS
I am or have been for years a member of the following organizations and boards: EMBO (permanent Member), International Affairs Committee of the American Society of Cell Biology, AIRC Scientific Committee, Review Panel of the EMBL Core Facilities and Technologies, EuroBioImaging, ERC Advanced Evaluation Panel, Academia Europea, Emilio Trabucchi Foundation Medal, Nominator for the Nobel Prize and the Japan Prize.
MANAGERIAL ACTIVITIES
Co-founder of the Consorzio Mario Negri Sud Research Institute, initiator of the Open University
Ph.D. Programme at the Mario Negri Sud Institute, co-founder and first coordinator of ELMI (European
Light Microscopy Initiative), member of the EuroBioimaging interim board and founder of the CNR EuroBioimaging Facility, co-founder of the Campania Imaging Infrastructure for Research in Oncology (CIRO); Co-founder of the Telethon Initiative for the Discovery of Drug Targets.
MENTORING ACTIVITIES
A number of my PhD students and postdocs are now heads of laboratory or heads of department in prestigious national and international institutions such as the NIH (Washington), Friedrich Miescher (Basel), University of Santiago , Seoul, Manchester, Montpellier, IFOM (Milano), TIGEM (Naples), CNR, ISS (Rome) etc. Some of them are or have been editors or chief editors of major scientific journals like EMBO Journal and Journal of Experimental Medicine. One, Teo Pulvirenti, is Editorial Director of Rockefeller Press.
1-Golgi maturation-dependent glycoenzyme recycling controls glycosphingolipid biosynthesis and cell growth via GOLPH3. Rizzo R, Russo D, Kurokawa K, Sahu P, Lombardi B, Supino D, Zhukovsky MA, Vocat A, Pothukuchi P, Kunnathully V, Capolupo L, Boncompain G, Vitagliano C, Zito Marino F, Aquino G, Montariello D, Henklein P, Mandrich L, Botti G, Clausen H, Mandel U, Yamaji T, Hanada K, Budillon A, Perez F, Parashuraman S, Hannun YA, Nakano A, Corda D, D'Angelo G, Luini A.
EMBO J. 2021 Apr 15;40(8):e107238.
2-Auto-regulation of Secretory Flux by Sensing and Responding to the Folded Cargo Protein Load in the Endoplasmic Reticulum.
Subramanian A, Capalbo A, Iyengar NR, Rizzo R, di Campli A, Di Martino R, Lo Monte M, Beccari AR, Yerudkar A, Del Vecchio C, Glielmo L, Turacchio G, Pirozzi M, Kim SG, Henklein P, Cancino J, Parashuraman S, Diviani D, Fanelli F, Sallese M, Luini A.
Cell. 2019 Mar 7;176(6):1461-1476.e23.
3-A traffic-activated Golgi-based signalling circuit coordinates the secretory pathway.
Pulvirenti T, Giannotta M, Capestrano M, Capitani M, Pisanu A, Polishchuk RS, San Pietro E, Beznoussenko GV, Mironov AA, Turacchio G, Hsu VW, Sallese M, Luini A.
Nat Cell Biol. 2008 Aug;10(8):912-22.
4-Correlative Light-Electron Microscopy Reveals the Tubular-Saccular Ultrastructure of Carriers Operating between Golgi Apparatus and Plasma Membrane
Roman S. Polishchuk, Elena V. Polishchuk, Pierfrancesco Marra, Saverio Alberti, Roberto Buccione, Alberto Luini, and Alexander A. Mironov
J Cell Biol. 2000; 148(1): 45–58.
5-The dynamics of engineered resident proteins in the mammalian Golgi complex relies on cisternal maturation.
Rizzo R, Parashuraman S, Mirabelli P, Puri C, Lucocq J, Luini A.
J Cell Biol. 2013 Jun 24;201(7):1027-36
6-Mendelian disorders of membrane trafficking
Maria Antonietta De Matteis, Alberto Luini
N Engl J Med. 2011;365(10):927-38.
7- Procollagen traverses the Golgi stack without leaving the lumen of cisternae: evidence for cisternal maturation. L Bonfanti , A A Mironov Jr, J A Martínez-Menárguez, O Martella, A Fusella, M Baldassarre, R Buccione, H J Geuze, A A Mironov, A Luini.
Cell. 1998 Dec 23;95(7):993-1003.
Researchers:
Domenico Russo d.russo@ieos.cnr.it
Francesco Russo f.russo@ieos.cnr.it
Rosaria Di Martino r.dimartino@ieos.cnr.it
Mikhail Zhukovsky m.zhukovsky@ieos.cnr.it
Post-doc fellows:
Matteo Lo Monte m.lomonte@ieos.cnr.it
Vincenzo Manuel Marzullo vincenzomanuel.marzullo@ieos.cnr.it
Pranoy Sahu p.sahu@ieos.cnr.it
Balakrishnan Aswath balakrishnana.aswath@ieos.cnr.it
Cristiano Russo c.russo@ieos.cnr.it
Fellow:
Valentina De Luca v.deluca@ieos.cnr.it
PhD students:
Seyedehnegar Parizadeh n.parizadeh@ieos.cnr.it
Lab Manager:
Luigi Concilio l.concilio@ieos.cnr.ii
2019-2023: H2020-MSCA-ITN-2019 – MSCA-ITN-ETN “Exploitation of the SECRETory pathway for cancer therapy to address European research”
2012-pending: Italian Node of Euro-Bioimaging (Preparatory Phase II – INFRADEV) Progetto di costruzione e mantenimento dei Nodi italiani di Euro-Bioimaging
2018-2022: Italian Foundation for Cancer Research AIRC IG 15767 “Dissecting and targeting the oncogenic molecular mechanism of action of GOLPH3”
2018-2022: POR CAMPANIA - PLATT “Innovative platform for the development of new radiopharmaceuticals for diagnosis and treatment of solid malignancies and novel potent non-invasive methods for the diagnosis and management of lung cancer”
2014-2020: POR Campania “Campania Imaging Infrastructure for Research in Oncology” C.I.R.O
2018-2020: POR Campania, “Sviluppo di Approcci Terapeutici Innovativi per patologie Neoplastiche resistenti ai trattamenti – SATIN”
2015-2017: Italian Foundation for Cancer Research AIRC IG 20786 “Cancer-relevant molecular pathways in the intracellular membrane transport apparatus”
2014-2018: Italian Cystic Fibrosis Research Foundation (Project #6)
2014-2015: Progetto Medintech- Cluster Alisei "Tencologie convergenti per aumentare la sicurezza e l'efficacia di farmaci e vaccini"
2010-2015: PON01_00117 “Antigeni e adiuvanti per vaccini e immunoterapia”
2011-2014: MIUR FaReBio di Qualità “Farmaci e reti biotecnologiche di qualita’, un laboratorio senza mura di piccoli organismi modello per un programma innovativo di supporto alla produzione di farmaci biotecnologici e alla nuova tossicologia.
2010-2015 PON01_00862 "Una piattaforma tecnologica integrata per lo sviluppo di nuovi farmaci per malattie rare"
Golgi maturation-dependent glycoenzyme recycling controls glycosphingolipids biosynthesis and cell growth via GOLPH3
Access to the paper:
https://www.embopress.org/doi/full/10.15252/embj.2020107238
AREX, uno dei sistemi che controllano il traffico delle proteine
Chiarito un meccanismo molecolare che regola il trasporto delle proteine cellulari destinate all'esportazione al di fuori della cellula a partire dal reticolo endoplasmico. Anomalie in questo meccanismo potrebbero contribuire allo sviluppo di tumori.
Access to the paper:
https://pubmed.ncbi.nlm.nih.gov/30849374/
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https://www.airc.it/traguardi-dei-ricercatori/arex-uno-dei-sistemi-che-controllano-il-traffico-delle-proteine
