Neuroscience Division

Prof Giorgia Melli, MD, PhD
Principal Investigator
ORCID: 0000-0003-2069-4620

Elena Vacchi, PhD, Post doc
ORCID: 0000-0002-8419-277X

Sandra Pinton
Senior Researcher
ORCID: 0000-0001-7242-4986

Domenico Dell’Aversana, MD visiting Post doc fellow
ORCID: 0009-0000-4847-0958

Ankush Yadav, PhD student
ORCID: 0000-0003-4455-9597

Rafailia Christou, PhD student

Francesco Ruggiero, MD Clinical Researcher

Silvia Fumagalli, Lab Technician

Research and translational research

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease associated with intra-neuronal accumulation of aggregated alpha-synuclein (α-Syn) protein, but unfortunately current knowledge still does not address the underlying pathogenic mechanisms.

Consequently, PD lacks both an effective causal treatment and definitive early diagnostic criteria. In the recent years a large amount of evidence has shown that peripheral tissues like skin autonomic nerves, gastro-intestinal mucosa, salivary glands show immunoreactivity to pathogenic forms of α-Syn. Thus, peripheral tissues, that can be easily biopsied, contain nervous tissue prone to the pathology, and bear potentially important information on disease mechanisms.

Our laboratory has a strong translational attitude and aims to set-up novel pathway biomarkers of disease by analyzing skin biopsy and peripheral fluids via advanced new biotechnology.

Our group has published several papers on the detection/characterization of α-Syn and its pathogenic species in the skin of PD and other neurodegenerative diseases like atypical parkinsonisms plus we demonstrated that PD patients present a somatosensory small fiber neuropathy that correlates with disease duration and progression. More recently we published several papers on the specific profile of surface proteins of blood- and CSF-derived extracellular vesicles (EVs), which stratifies patients with PD and atypical parkinsonisms.

These EV markers are related to circulating inflammatory and immune cells. We are now profiling prodromal and early phases of disease to identify specific signature and we are investigating how peripheral inflammation and immune dysregulation can contribute to brain neuronal cell death in PD. These projects take advantage of a biobank and clinical database for PD and atypical parkinsonisms that the PI Giorgia Melli established at NSI in Lugano since 2015.

Research methods

Our laboratory is a multidisciplinary laboratory dedicated to the study of patients-derived peripheral samples (skin, blood, and CSF) by the means of advanced technology in the field of histology, biochemistry, and high throughput proteomics.

We set up a proximity ligation assay, and confocal microscopy protocols for the analysis and quantification of several neuronal and aggregation prone proteins for skin biopsy specimens.

We set up a standardized protocol for high resolution mass spectrometry (MS) based proteomics analysis of skin lysates. Moreover, we exploit standardized human peripheral blood mononuclear cell (PBMC) isolation and culture methods and neuronal cell lines culture protocols for the analysis of peripheral inflammation in patients with PD and atypical parkinsonisms at different stages of disease.

• Structure of ATTRv-F64S fibrils isolated from skin tissue of a living patient.
  Yu J, Zhang X, Pinton S, Vacchi E,Cavalli A, Pecoraro M, Melli G & Boland A. Nature Communications 16 December 25, https://www.nature.com/articles/s41467-025-67457-2
• JNK3 quantification in plasma: a novel biomarker for neuronal damage in Parkinson’s disease.
  Vacchi E, Giani A, Perta N, Turchetti S, Pasetto L, Bonetto V, Bacalini MG, Baldelli L, Provini F, Hackethal S, Riccardi S, Miano S, Manconi M, Kägi G, Bertaina I, Bianco G, Galati S, Kaelin-Lang A, Raimondo D, Repici M, Tettamanti M, Melli G, Borsello T.NPJ Parkinsons Dis. 2025 Dec 10. doi: 10.1038/s41531-025-01224-4. Online ahead of print.PMID: 41372194
• Updated recommendations for the treatment of light-chain amyloidosis from the Swiss Amyloidosis Network.
  Rieger MJ, Flammer AJ, Gerull S, Pabst T, Auner HW, Samii K, Hitz F, Mey U, Ballova V, Battegay R, Melli G, Benz D, Yakupoglu Y, Gräni C, Schläger R, Hugelshofer S, Studer A, Oechslin L, Bakula A, Suter TM, Leo-Stickelberger J, Averiamo M, Fehr T, Jung HH, Laptseva N, Manka R, Rüfer A, Schmidt A, Seeger H, Müllhaupt B, Stämpfli SF, De Ramon Ortiz C, Théaudin M, Gerber B, Schwotzer R.Swiss Med Wkly. 2025 Jul 17;155:4219. doi: 10.57187/s.4219.PMID: 40811214
• α-synuclein biomarker assays: bridging research and patient care.
  Agin-Liebes J, Lodge A, Reddy H, Vacchi E, Usseglio J, Honig LS, Melli G, Noble JM, Przedborski S.Lancet Neurol. 2025 Aug;24(8):681-697. doi: 10.1016/S1474-4422(25)00194-2.PMID: 40683277 Review
• Tau biomarkers for neurodegenerative diseases: Current state and perspectives.
  Vacchi E, Ruiz-Barrio I, Melli G.Parkinsonism Relat Disord. 2025 May;134:107772. doi: 10.1016/j.parkreldis.2025.107772. Epub 2025 Mar 10.PMID: 40185651
• The Effect of Repetitive Transcranial Magnetic Stimulation Treatment on Plasma BDNF Concentration and Executive Functions in Parkinson’s Disease: A Theoretical Translational Medicine Approach.
  Riccitelli GC, Gironi R, Melli G, Kaelin-Lang A.Int J Mol Sci. 2025 Jan 30;26(3):1205. doi: 10.3390/ijms26031205.PMID: 39940980
• Tau seeding activity in skin biopsy differentiates tauopathies from synucleinopathies
  Dellarole I, Vacchi E, Ruiz-Barrio I, Pinton S, Raimondi A, Rossi S, Morandi S, Bianco G, Begum Bacinoglu M, Lombardo A, Celauro L, Staedler C, Galati S, Pagonabarraga J, Kulisevsky J, Legname G, Gobbi C, Kaelin-Lang A, Moda F, Melli G. NPJ Parkinsons Dis. 2024 Jun 15;10(1):116. doi: 10.1038/s41531-024-00728-9.
• Amyloid detection and typing yield of skin biopsy in systemic amyloidosis and polyneuropathy
  Pinton S, Vacchi E, Chiaro G, Raimondi A, Tzankov A, Gerber B, Gobbi C, Kaelin-Lang A, Melli G. Ann Clin Transl Neurol. 2023 Dec;10(12):2347-2359. doi:10.1002/acn3.51924. Epub 2023 Oct 18.
• Tau protein quantification in skin biopsies differentiates tauopathies from alpha-synucleinopathies
  Vacchi E, Lazzarini E, Pinton S, Chiaro G, Disanto G, Marchi F, Robert T, Staedler C, Galati S, Gobbi C, Barile L, Kaelin-Lang A, Melli G. Brain.
  Volume 145, Issue 8, August 2022, Pages 2755–2768, https://doi.org/10.1093/brain/awac161
• Alpha-synuclein oligomers and small nerve fiber pathology in skin are potential biomarkers of Parkinson’s disease
  Vacchi E, Senese C, Chiaro G, Disanto G, Pinton S, Morandi S, Bertaina I, Bianco G, Stadler C, Galati S, Gobbi C, Kaelin-Lang A, Melli G.
  npj Parkinsons Dis. 7, 119 (2021). doi: 10.1038/s41531-021-00262-y
• Alpha-synuclein oligomers and small nerve fiber pathology in skin are potential biomarkers of Parkinson’s disease
  Vacchi E, Burrello J, Burrello A, Bolis S, Monticone S, Barile L, Kaelin-Lang A, Melli G. Biomedicines. 2021 Feb 25;9(3):230. doi: 10.3390/biomedicines9030230
• Profiling Inflammatory Extracellular Vesicles in Plasma and Cerebrospinal Fluid: An Optimized Diagnostic Model for Parkinson’s Disease
  Vacchi E, Burrello J, Di Silvestre D, Burrello A, Bolis S, Mauri PL, Vassalli G, Cereda CW, Farina C, Barile L, Kaelin-Lang A, Melli G.
  Neurol Neuroimmunol Neuroinflamm 2020 Aug 12;7(6):e866. doi: 10.1212/NXI.0000000000000866
• Tau and Alpha Synuclein Synergistic Effect in Neurodegenerative Diseases: When the Periphery Is the Core
  Vacchi E. Kaelin-Lang A and Melli G.
  Int J Mol Sci . 2020 Jul 16;21(14):5030. doi: 10.3390/ijms21145030
• Targeting Alpha Synuclein Aggregates in Cutaneous Peripheral Nerve Fibers by Free-floating Immunofluorescence Assay
  Vacchi E, Pinton S, Kaelin-Lang A, Melli G.
  J Vis Exp. 2019 Jun 25;(148). doi: 10.3791/59558.
• Cervical skin denervation associates with alpha-synuclein aggregates in Parkinson disease
  Melli G, Vacchi E, Biemmi V, Galati S, Staedler C, Ambrosini R, Kaelin-Lang A.
  Ann Clin Transl Neurol. 2018 Oct 14;5(11):1394-1407. doi: 10.1002/acn3.669

PUBLICATIONS IN COLLABORATIONS WITH OTHER GROUPS

• The Effect of Repetitive Transcranial Magnetic Stimulation Treatment on Plasma BDNF Concentration and Executive Functions in Parkinson’s Disease: A Theoretical Translational Medicine Approach.
  Riccitelli G., Gironi R., Melli G., Kaelin-Lang A.
  Int J Mol Sci (IF: 4.56; Q1). 2025 Jan 30;26(3):1205. doi: 10.3390/ijms26031205.
• Age- and sex-related variations in extracellular vesicle profiling for the assessment of cardiovascular risk: the EVaging index 
  Burrello J., Goi J., Burrello A., Vacchi E., Rendon-Angel A., Lazzarini E., Bianco G., Limongelli V., Vassalli G., Cereda C., Monticone S., Mulatero P., Bussolati B., Alimonti A., Camici G., Melli G., Osto E., Pedrazzini G., Barile L.
  NPJ Aging. 2024 Dec 19;10(1):63. doi: 10.1038/s41514-024-00189-7
• Skin Tau Quantification as a Novel Biomarker in Huntington’s Diseases
  Ruiz-Barrio I, Vázquez-Oliver A, Puig-Davi A, Rivas-Asensio E, Perez-Perez J, Fernandez-Vizuete C, Horta-Barba A, Olmedo-Saura G, Salvat-Rovira N, Sampedro F, Vacchi E, Melli G, Pagonabarraga J, Kulisevsky J, Martinez-Horta S.
  Mov Disord. 2024 Aug 28. doi: 10.1002/mds.29989. Online ahead of print.
• Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches
  Welsh J A, Goberdhan D C I, O’Driscoll L, Buzas E I, Blenkiron C, Bussolati B, Cai H, Di Vizio D, P Driedonks T A P, Erdbrügger U, Falcon-Perez J M, Fu QL, Hill A F, Lenassi M, Kiang Lim S, Mahoney M G, Mohanty S, Möller A, Nieuwland R, Ochiya T, Sahoo S, Torrecilhas A C, Zheng L, Zijlstra A, Abuelreich S, Bagabas R, Bergese P, Bridges E M, Brucale M, Burger D, Carney R P, Cocucci E, Crescitelli R, Hanser E, Harris A L, Haughey N J, Hendrix A, Ivanov A R, Jovanovic-Talisman T, Kruh-Garcia N A, Ku’ulei-Lyn Faustino V, Kyburz D, Lässer C, Lennon K M, Lötvall J, Maddox A L, Martens-Uzunova E S, Mizenko R R, Newman L A, Ridolfi A, Rohde E, Rojalin T, Rowland A, Saftics A, Sandau U S, Saugstad J A, Shekari F, Swift S, Ter-Ovanesyan D,Tosar J P, Useckaite Z, Valle F, Varga Z, van der Pol E, van Herwijnen MJC, Wauben MHM, Wehman A M, Williams S, Zendrini A, Zimmerman A J; MISEV Consortium; Théry C, Witwer K W.
  J Extracell Vesicles. 2024 Feb;13(2): e12404. doi: 10.1002/jev2.12404
• Prevalence of amyloid in ligamentum flavum of patients with lumbar spinal stenosis
  Marchi F, Kessler C, Distefano D, Terzi di Bergamo L, Fumagalli L, Averaimo M, Crupi E, Bergamini F, Melli G, Stuessi G, Rossi D, Gobbi C, Ripellino P, Pravatà E, Kuhlen D E, Röcken C, Scarone P, Gerber B, Condoluci A.
  Amyloid. 2023 Dec;30(4):416-423. doi: 10.1080/13506129.2023.2230516. Epub 2023 Jul 11.
• Dorsal Root Ganglion Stimulation in Chronic Painful Polyneuropathy: A Potential Modulator for Small Nerve Fiber Regeneration
  Koetsier E, Vacchi E, Maino P, Dukanac J, Melli G, van Kuijk S. Neuromodulation. 2022 Sep 30;S1094-7159(22)01252-1. doi: 10.1016/j.neurom.2022.08.455.
• Supervised and unsupervised learning to define the cardiovascular risk of patients according to an extracellular vesicle molecular signature
  Burrello J, Burrello A, Vacchi E, Bianco G, Caporali E, Amongero M, Airale L, Bolis S, Vassalli G, Cereda C.W, Mulatero P, Bussollati B, Camici G, Melli G, Monticone S, Barile L. Transl Res. 2022 Jun;244:114-125. doi: 10.1016/j.trsl.2022.02.005
• Circulating extracellular vesicles are endowed with enhanced procoagulant activity in SARS-CoV-2 infection
  Balbi C, Burrello J, Bolis S, Lazzarini E, Biemmi V, Pianezzi E, Burrello A, Caporali E, Grazioli LG, Martinetti G, Fusi-Schmidhauser T, Vassalli G, Melli G, Barile L. EBioMedicine. 2021 May;67:103369. doi: 10.1016/j.ebiom.2021.103369
• Extracellular Vesicle Surface Markers as a Diagnostic Tool in Transient Ischemic Attacks
  Burrello J, Bianco G, Burrello A, Manno C, Maulucci F, Padlina G, Nannoni S, Michel P, Bolis S, Melli G, Vassalli G, Albers GW, Cianfoni A, Barile L, Cereda CW. Stroke. 2021 Oct;52(10):3335-3347. doi: 10.1161/STROKEAHA.120.033170

Complete list of publications: orcid.org