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Institute for Research in Biomedicine
Istituto di Ricerca in Biomedicina

Via Vincenzo Vela 6 - CH-6500 Bellinzona
Tel. +41 91 820 0300 - Fax +41 91 820 0302 - info [at] irb [dot] usi [dot] ch

Maurizio Molinari, PhD

Controllo della produzione proteica

Direttore di laboratorio

Via Vela, 6
6500 Bellinzona, Switzerland

Maurizio Molinari
Bio

Maurizio Molinari ha ricevuto il dottorato in Biochimica al Politecnico Federale di Zurigo nel 1995. Nel 1996-1997 ha lavorato come post-doc nel laboratorio di Cesare Montecucco al Dipartimento di Biomedicina dell’Università di Padova. Tra il 1998 e il 2000 è stato assistente nel laboratorio di Ari Helenius al Politecnico Federale di Zurigo. Dall’ottobre 2000, è Direttore di laboratorio all’IRB. Gli studi effettuati nel suo gruppo hanno dato un contributo significativo alla comprensione dei meccanismi che permettono la produzione delle proteine nelle cellule di mammifero e dei meccanismi che permettono alle cellule di eliminare proteine difettose, potenzialmente tossiche. Questi studi hanno permesso, tra l’altro, di mettere a punto un nuovo approccio terapeutico basato sull’utilizzo di mini-anticorpi che permette di contrastare la produzione di beta-amiloide, un peptide il cui accumulo causa processi neurodegenerativi associati con la malattia di Alzheimer. Hanno anche portato alla caratterizzazione di un nuovo meccanismo autofagico che permette alle cellule di riprendersi da stress causati dall’accumulo di aggregati proteici tossici distruggendo gli organelli che li contengono. Maurizio Molinari ha ricevuto lo Science Award 2002 della Fondazione per lo Studio delle Malattie Neurodegenerative, il Kiwanis Club Award 2002 per le Scienze Biomediche, il Friedrich-Miescher Award 2006, il Research Award Aetas 2007 e il Regli Foundation Award 2013. Nel 2008 è stato nominato Professore Associato al Politecnico Federale di Losanna. Nel settembre 2012 è stato nominato commissario per l’insegnamento della chimica e della biologia presso le Scuole Superiori nel Cantone Ticino e dal gennaio 2013 è membro della Commissione per la Ricerca Scientifica presso l'Università della Svizzera italiana. Dal 2017 è anche un International Ambassador of the American Society for Cell Biology.

Progetti
Substrate-Specific Mechanisms of Protein Degradation from the ER
Novel Protein Quality Checkpoints
Disposal of Non-Glycosylated Polypeptides from the Mammalian ER
Cellular Responses to Variations in ER Homeostasis and Protein Load
Generating Antibodies to Contrast Aβ Deposition
Revealing Mechanisms Regulating Recovery from Transient ER Stress in Mammalian Cells
The Function and Regulation of ER-Phagy During ER Homeostasis and Stress
Role of Membrane-Bound Oxidoreductases in Protein Biogenesis
Comparative Interactomics to Identify Novel ER-Resident Quality Control Players
Pubblicazioni
ER-to-lysosome-associated degradation of proteasome-resistant ATZ polymers occurs via receptor-mediated vesicular transport
I. Fregno, E. Fasana, T. J. Bergmann, A. Raimondi, M. Loi, T. Solda, C. Galli, R. D'Antuono, D. Morone, A. Danieli, P. Paganetti, E. van Anken, M. Molinari
in EMBO J (2018) vol. 37 pp e99259
Three branches to rule them all? UPR signaling in response to chemically- versus misfolded proteins-induced ER stress
T. J. Bergmann, M. Molinari
in Biol Cell (2018) vol. 110 pp197-204
The reductase TMX1 contributes to ERAD by preferentially acting on membrane-associated folding-defective polypeptides
C. Guerra, G. Brambilla Pisoni, T. Solda, M. Molinari
in Biochem Biophys Res Commun (2018) pp938 - 943
Eat it right: ER-phagy and recovER-phagy
M. Loi, I. Fregno, C. Guerra, M. Molinari
in Biochem Soc Trans (2018) pp699–706
Endoplasmic reticulum turnover: ER-phagy and other flavors in selective and non-selective ER clearance
I. Fregno, M. Molinari
in F1000Res (2018) vol. 7 pp454
Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides
T. J. Bergmann, I. Fregno, F. Fumagalli, A. Rinaldi, F. Bertoni, P. J. Boersema, P. Picotti, M. Molinari
in J Biol Chem (2018) vol. 293 pp5600-5612
Role of SEC62 in ER maintenance: A link with ER stress tolerance in SEC62-overexpressing tumors?
T. J. Bergmann, F. Fumagalli, M. Loi, M. Molinari
in Mol Cell Oncol (2017) vol. 4 ppe1264351
Quality control mechanisms of protein biogenesis: proteostasis dies hard
T. J. Bergmann, G. Brambilla Pisoni, M. Molinari
in AIMS Biophysics (2016) vol. 3 pp456-478
Translocon component Sec62 acts in endoplasmic reticulum turnover during stress recovery
F. Fumagalli, J. Noack, T. J. Bergmann, E. C. Presmanes, G. B. Pisoni, E. Fasana, I. Fregno, C. Galli, M. Loi, T. Solda, R. D'Antuono, A. Raimondi, M. Jung, A. Melnyk, S. Schorr, A. Schreiber, L. Simonelli, L. Varani, C. Wilson-Zbinden, O. Zerbe, K. Hofmann, M. Peter, M. Quadroni, R. Zimmermann, M. Molinari
in Nat Cell Biol (2016) vol. 18 pp1173-1184
Fumagalli, F. , Noack J. and Bergmann T. contributed equally to this work. * Recommended by the Faculty of 1000
Post ER Quality Control: A Role for UDP-Glucose:Glycoprotein Glucosyl Transferase and p97
I. Fregno, M. Molinari
in J Rare Dis Res & Treatment (2016) vol. 1 pp40-42
Five Questions (with their Answers) on ER-Associated Degradation
G. Brambilla Pisoni, M. Molinari
in Traffic (2016) vol. 17 pp341-50
Guidelines for the use and interpretation of assays for monitoring autophagy
D. J. Klionsky, M. Molinari, et al.
in Autophagy (2016) vol. 12 pp1-222
Division of labor among oxidoreductases: TMX1 preferentially acts on transmembrane polypeptides
G. B. Pisoni, L. W. Ruddock, N. Bulleid, M. Molinari
in Mol Biol Cell (2015) vol. 26 pp3390-400
The Protein-disulfide Isomerase ERp57 Regulates the Steady-state Levels of the Prion Protein
M. Torres, D. B. Medinas, J. M. Matamala, U. Woehlbier, V. H. Cornejo, T. Solda, C. Andreu, P. Rozas, S. Matus, N. Munoz, C. Vergara, L. Cartier, C. Soto, M. Molinari, C. Hetz
in J Biol Chem (2015) vol. 290 pp23631-45
Glycoprotein maturation and quality control
M. Molinari, D. N. Hebert
in Semin Cell Dev Biol (2015) vol. 41 pp70
A novel UGGT1 and p97-dependent checkpoint for native ectodomains with ionizable intramembrane residue
J. Merulla, T. Solda, M. Molinari
in Mol Biol Cell (2015) vol. 26 pp1532-42
* Recommended by the Faculty of 1000
N-linked sugar-regulated protein folding and quality control in the ER
A. Tannous, G. B. Pisoni, D. N. Hebert, M. Molinari
in Semin Cell Dev Biol (2015) vol. 41 pp79-89
Protein trafficking: RESETting proteostasis
J. Noack, M. Molinari
in Nat Chem Biol (2014) vol. 10 pp881-2
Proteostasis: Bad news and good news from the endoplasmic reticulum
J. Noack, G. Brambilla Pisoni, M. Molinari
in Swiss Med Wkly (2014) vol. 144 ppw14001
How viruses hijack the ERAD tuning machinery
J. Noack, R. Bernasconi, M. Molinari
in J Virol (2014) vol. 88 pp10272-5
Correction to the paper can be found here: http://jvi.asm.org/content/89/7/4040.long
Non-Lipidated LC3 is Essential for Mouse Hepatitis Virus Infection
J. Noack, R. Bernasconi, M. Molinari
M. A. Hayat
in Autophagy (2014) vol. 2 pp129-136
Transgenic expression of beta1 antibody in brain neurons impairs age-dependent amyloid deposition in APP23 mice
P. Paganetti, J. Reichwald, D. Bleckmann, D. Abramowski, D. Ammaturo, C. Barske, S. Danner, M. Molinari, M. Muller, S. Papin, S. Rabe, P. Schmid, M. Staufenbiel
in Neurobiol Aging (2013) vol. 34 pp2866-78
UDP-glucose:glycoprotein glucosyltransferase (UGGT1) promotes substrate solubility in the endoplasmic reticulum
S. P. Ferris, N. S. Jaber, M. Molinari, P. Arvan, R. J. Kaufman
in Mol Biol Cell (2013) vol. 24 pp2597-2608
Specificity and regulation of the endoplasmic reticulum-associated degradation machinery
J. Merulla, E. Fasana, T. Solda, M. Molinari
in Traffic (2013) vol. 14 pp767-77
Endoplasmic Reticulum-Associated Protein Degradation
R. Bernasconi, M. Molinari
W.J. Lennarz, M.D. Lane, Editors
in Encyclopedia of Biological Chemistry (2013) vol. 2 pp200-203
Flagging and docking: dual roles for N-glycans in protein quality control and cellular proteostasis
D. N. Hebert, M. Molinari
in Trends Biochem Sci (2012) vol. 37 pp404-10
Unconventional roles of nonlipidated LC3 in ERAD tuning and coronavirus infection
R. Bernasconi, J. Noack, M. Molinari
in Autophagy (2012) vol. 8 pp1534-6
Unconventional Use of LC3 by Coronaviruses through the Alleged Subversion of the ERAD Tuning Pathway
F. Reggiori, C. A. de Haan, M. Molinari
in Viruses (2011) vol. 3 pp1610-23
Chronic delivery of antibody fragments using immunoisolated cell implants as a passive vaccination tool
O. Marroquin Belaunzaran, M. I. Cordero, V. Setola, S. Bianchi, C. Galli, N. Bouche, V. Mlynarik, R. Gruetter, C. Sandi, J. C. Bensadoun, M. Molinari, P. Aebischer
in PLoS One (2011) vol. 6 ppe18268
Malectin Participates in a Backup Glycoprotein Quality Control Pathway in the Mammalian ER
C. Galli, R. Bernasconi, T. Solda, V. Calanca, M. Molinari
in PLoS One (2011) vol. 6 ppe16304
ERAD and ERAD tuning: disposal of cargo and of ERAD regulators from the mammalian ER
R. Bernasconi, M. Molinari
in Curr Opin Cell Biol (2011) vol. 23 pp176-183
Cyclosporine a-sensitive, cyclophilin B-dependent endoplasmic reticulum-associated degradation
R. Bernasconi, T. Solda, C. Galli, T. Pertel, J. Luban, M. Molinari
in PLoS One (2010) vol. 5 ppe13008
Autophagy-independent LC3 function in vesicular traffic
C. A. de Haan, M. Molinari, F. Reggiori
in Autophagy (2010) vol. 6 pp994-6
Coronaviruses Hijack the LC3-I-positive EDEMosomes, ER-derived vesicles exporting short-lived ERAD regulators, for replication
F. Reggiori, I. Monastyrska, M. H. Verheije, T. Cali, M. Ulasli, S. Bianchi, R. Bernasconi, C. A. de Haan, M. Molinari
in Cell Host Microbe (2010) vol. 7 pp500-8
* Highlights in Cell Host & Microbe 7, 424-426; Editors’ Choice in Science 329, 14; Leading Edge, Microbiology Select in Cell 142, 5; Recommended by the Faculty of 1000
Stringent requirement for HRD1, SEL1L, and OS-9/XTP3-B for disposal of ERAD-LS substrates
R. Bernasconi, C. Galli, V. Calanca, T. Nakajima, M. Molinari
in J Cell Biol (2010) vol. 188 pp223-35
* Highlights in J. Cell Biol 188, 176
ERAD substrates: which way out?
D. N. Hebert, R. Bernasconi, M. Molinari
in Semin Cell Dev Biol (2010) vol. 21 pp526-32
N-glycan structures: recognition and processing in the ER
M. Aebi, R. Bernasconi, S. Clerc, M. Molinari
in Trends Biochem Sci (2010) vol. 35 pp74-82
The endoplasmic reticulum crossroads for newly synthesized polypeptide chains
T. Cali, O. Vanoni, M. Molinari
in Prog Mol Biol Transl Sci (2008) vol. 83 pp135-79
Consequences of individual N-glycan deletions and of proteasomal inhibition on secretion of active BACE
O. Vanoni, P. Paganetti, M. Molinari
in Mol Biol Cell (2008) vol. 19 pp4086-98
Segregation and rapid turnover of EDEM1 by an autophagy-like mechanism modulates standard ERAD and folding activities
T. Cali, C. Galli, S. Olivari, M. Molinari
in Biochem Biophys Res Commun (2008) vol. 371 pp405-10
A dual task for the Xbp1-responsive OS-9 variants in the mammalian endoplasmic reticulum: inhibiting secretion of misfolded protein conformers and enhancing their disposal
R. Bernasconi, T. Pertel, J. Luban, M. Molinari
in J Biol Chem (2008) vol. 283 pp16446-54
ER-Associated Folding and Degradation: Learning From Yeast?
R. Bernasconi, M. Molinari
C.B. O’Doherty, A.C. Byrne, Editors
in Protein misfolding (2008) pp113-123
In and out of the ER: protein folding, quality control, degradation, and related human diseases
D. N. Hebert, M. Molinari
in Physiol Rev (2007) vol. 87 pp1377-408
Substrate-specific requirements for UGT1-dependent release from calnexin
T. Solda, C. Galli, R. J. Kaufman, M. Molinari
in Mol Cell (2007) vol. 27 pp238-49
N-glycan structure dictates extension of protein folding or onset of disposal
M. Molinari
in Nat Chem Biol (2007) vol. 3 pp313-20
Glycoprotein folding and the role of EDEM1, EDEM2 and EDEM3 in degradation of folding-defective glycoproteins
S. Olivari, M. Molinari
in FEBS Lett (2007) vol. 581 pp3658-64
N-glycan processing in ER quality control
L. W. Ruddock, M. Molinari
in J Cell Sci (2006) vol. 119 pp4373-80
Microbiology: death of a chaperone
C. Montecucco, M. Molinari
in Nature (2006) vol. 443 pp511-2
EDEM1 regulates ER-associated degradation by accelerating de-mannosylation of folding-defective polypeptides and by inhibiting their covalent aggregation
S. Olivari, T. Cali, K. E. Salo, P. Paganetti, L. W. Ruddock, M. Molinari
in Biochem Biophys Res Commun (2006) vol. 349 pp1278-84
* Recommended by the Faculty of 1000
N-linked glycan recognition and processing: the molecular basis of endoplasmic reticulum quality control
K. W. Moremen, M. Molinari
in Curr Opin Struct Biol (2006) vol. 16 pp592-9
Consequences of ERp57 deletion on oxidative folding of obligate and facultative clients of the calnexin cycle
T. Solda, N. Garbi, G. J. Hammerling, M. Molinari
in J Biol Chem (2006) vol. 281 pp6219-26
The secretory capacity of a cell depends on the efficiency of endoplasmic reticulum-associated degradation
M. Molinari, R. Sitia
in Curr Top Microbiol Immunol (2005) vol. 300 pp1-15
Persistent glycoprotein misfolding activates the glucosidase II/UGT1-driven calnexin cycle to delay aggregation and loss of folding competence
M. Molinari, C. Galli, O. Vanoni, S. M. Arnold, R. J. Kaufman
in Mol Cell (2005) vol. 20 pp503-12
The use of calnexin and calreticulin by cellular and viral glycoproteins
M. Pieren, C. Galli, A. Denzel, M. Molinari
in J Biol Chem (2005) vol. 280 pp28265-71
The glycan code of the endoplasmic reticulum: asparagine-linked carbohydrates as protein maturation and quality-control tags
D. N. Hebert, S. C. Garman, M. Molinari
in Trends Cell Biol (2005) vol. 15 pp364-70
beta-site specific intrabodies to decrease and prevent generation of Alzheimer's Abeta peptide
P. Paganetti, V. Calanca, C. Galli, M. Stefani, M. Molinari
in J Cell Biol (2005) vol. 168 pp863-8
* Comments in NIBR Science Summer 2005
Degradation of trafficking-defective long QT syndrome type II mutant channels by the ubiquitin-proteasome pathway
Q. Gong, D. R. Keeney, M. Molinari, Z. Zhou
in J Biol Chem (2005) vol. 280 pp19419-25
Analyzing folding and degradation of metabolically labelled polypeptides by conventional and diagonal sodium dodecyl sulfate-polyacrylamide gel electrophoresis
T. Solda, S. Olivari, M. Molinari
in Biol Proced Online (2005) vol. 7 pp136-43
A novel stress-induced EDEM variant regulating endoplasmic reticulum-associated glycoprotein degradation
S. Olivari, C. Galli, H. Alanen, L. Ruddock, M. Molinari
in J Biol Chem (2005) vol. 280 pp2424-8
EDEM contributes to maintenance of protein folding efficiency and secretory capacity
K. K. Eriksson, R. Vago, V. Calanca, C. Galli, P. Paganetti, M. Molinari
in J Biol Chem (2004) vol. 279 pp44600-5
Contrasting functions of calreticulin and calnexin in glycoprotein folding and ER quality control
M. Molinari, K. K. Eriksson, V. Calanca, C. Galli, P. Cresswell, M. Michalak, A. Helenius
in Mol Cell (2004) vol. 13 pp125-35
Endoplasmic Reticulum-Associated Protein Degradation
M. Molinari
W.J. Lennarz, M.D. Lane, Editors
in Encyclopedia of Biological Chemistry (2004) vol. 2 pp20-23
The Protein Factory
M. Molinari
in Protocols of the 30th Seminars of Biological Evolution (2004) vol. 108 pp117-122
Role of EDEM in the release of misfolded glycoproteins from the calnexin cycle
M. Molinari, V. Calanca, C. Galli, P. Lucca, P. Paganetti
in Science (2003) vol. 299 pp1397-400
* Comments in Science 299, 1330-1331; Nature Reviews Molecular and Cellular Biology, 4, 259; Nature Structural and Molecular Biology, 10, 319-321; Recommended by the Faculty of 1000
Early postnatal death and motor disorders in mice congenitally deficient in calnexin expression
A. Denzel, M. Molinari, C. Trigueros, J. E. Martin, S. Velmurgan, S. Brown, G. Stamp, M. J. Owen
in Mol Cell Biol (2002) vol. 22 pp7398-404
Sequential assistance of molecular chaperones and transient formation of covalent complexes during protein degradation from the ER
M. Molinari, C. Galli, V. Piccaluga, M. Pieren, P. Paganetti
in J Cell Biol (2002) vol. 158 pp247-57
The disulphide bonds in the catalytic domain of BACE are critical but not essential for amyloid precursor protein processing activity
F. Fischer, M. Molinari, U. Bodendorf, P. Paganetti
in J Neurochem (2002) vol. 80 pp1079-88
Analyzing cotranslational protein folding and disulfide formation by diagonal sodium dodecyl sulfate-polyacrylamide gel electrophoresis
M. Molinari, A. Helenius
in Methods Enzymol (2002) vol. 348 pp35-42
Folding of viral glycoproteins in the endoplasmic reticulum
M. Molinari
in Virus Res (2002) vol. 82 pp83-6
Role of Molecular Chaperones in Viral Glycoprotein Folding
M. Molinari, A. Helenius
in Intracellular and persistent infections, Nobel Symposium (2001) vol. 106 pp1-10
Affinity purification of mu-calpain from erythrocytes on an immobilized peptide from the plasma membrane calcium pump. Some studies on erythrocyte mu-calpain
M. Molinari, E. Carafoli
in Methods Mol Biol (2000) vol. 144 pp41-6
Chaperone selection during glycoprotein translocation into the endoplasmic reticulum
M. Molinari, A. Helenius
in Science (2000) vol. 288 pp331-3
Site of Action and Cellular Effects Caused by the VacA Cytotoxin Released by Helicobacter pylori
M. de Bernard, E. Papini, M. Molinari, B. Satin, J. R. Telford, R. Rappuoli, C. Montecucco
J.E. Alouf, J.F. Freer, Editors
in Bacterial Toxins: A comprehensive Sourcebook (1999) pp1-27
Setting the standards: quality control in the secretory pathway
L. Ellgaard, M. Molinari, A. Helenius
in Science (1999) vol. 286 pp1882-8
Glycoproteins form mixed disulphides with oxidoreductases during folding in living cells
M. Molinari, A. Helenius
in Nature (1999) vol. 402 pp90-3
* News and Views in Nature 402, 27-29
The Helicobacter pylori neutrophil-activating protein is an iron-binding protein with dodecameric structure
F. Tonello, W. G. Dundon, B. Satin, M. Molinari, G. Tognon, G. Grandi, G. Del Giudice, R. Rappuoli, C. Montecucco
in Mol Microbiol (1999) vol. 34 pp238-46
Action site and cellular effects of cytotoxin VacA produced by Helicobacter pylori
E. Papini, B. Satin, M. de Bernard, M. Molinari, B. Arico, C. Galli, J. R. Telford, R. Rappuoli, C. Montecucco
in Folia Microbiol (Praha) (1998) vol. 43 pp279-84
The acid activation of Helicobacter pylori toxin VacA: structural and membrane binding studies
M. Molinari, C. Galli, M. de Bernard, N. Norais, J. M. Ruysschaert, R. Rappuoli, C. Montecucco
in Biochem Biophys Res Commun (1998) vol. 248 pp334-40
Calpain: a protease in search of a function?
E. Carafoli, M. Molinari
in Biochem Biophys Res Commun (1998) vol. 247 pp193-203
Selective inhibition of Ii-dependent antigen presentation by Helicobacter pylori toxin VacA
M. Molinari, M. Salio, C. Galli, N. Norais, R. Rappuoli, A. Lanzavecchia, C. Montecucco
in J Exp Med (1998) vol. 187 pp135-40
Vacuoles induced by Helicobacter pylori toxin contain both late endosomal and lysosomal markers
M. Molinari, C. Galli, N. Norais, J. L. Telford, R. Rappuoli, J. P. Luzio, C. Montecucco
in J Biol Chem (1997) vol. 272 pp25339-44
Calpain: a cytosolic proteinase active at the membranes
M. Molinari, E. Carafoli
in J Membr Biol (1997) vol. 156 pp1-8
Expression of the VacA Cytotoxin of Helicobacter pylori in the Cell Cytosol and Alteration of Membrane Trafficking
M. de Bernard, E. Papini, M. Molinari, B. Arico, B. Satin, C. Galli, J. R. Telford, R. Rappuoli, C. Montecucco
in Acta Med. Rom. (1997) vol. 35 pp625-633
Purification of active calpain by affinity chromatography on an immobilized peptide inhibitor
J. Anagli, E. M. Vilei, M. Molinari, S. Calderara, E. Carafoli
in Eur J Biochem (1996) vol. 241 pp948-54
Purification of mu-calpain by a novel affinity chromatography approach. New insights into the mechanism of the interaction of the protease with targets
M. Molinari, M. Maki, E. Carafoli
in J Biol Chem (1995) vol. 270 pp14576-81
PEST sequences do not influence substrate susceptibility to calpain proteolysis
M. Molinari, J. Anagli, E. Carafoli
in J Biol Chem (1995) vol. 270 pp2032-5
Ca(2+)-activated neutral protease is active in the erythrocyte membrane in its nonautolyzed 80-kDa form
M. Molinari, J. Anagli, E. Carafoli
in J Biol Chem (1994) vol. 269 pp27992-5