Research topics

The lab’s research interest is in the field of neuronal and endocrine cells physiopathology. We are interested in characterizing the molecular mechanisms of paracrine interactions among neuronal cells in the nervous system and endocrine cells in islet of Langerhans and in evaluating the dynamics of cellular responses. Our ultimate goal is to apply the information obtained through these studies toward the development of novel approaches for the treatment of nervous system pathologies and metabolic diseases.

Main projects:
1) Molecular mechanisms of synaptic transmission. We are interested in characterizing the role of LRRK2/parkin 8 in vesicular trafficking and synaptic activity and in understanding how modification of its activity/expression is related to Parkinson disease development.
2) Islets of Langerhans: We are interested in identifying the molecular mechanisms controlling beta-cell proliferation, differentiation, function in physiological conditions and understanding how these signaling pathways may be modified in pathological states (diabetes mellitus, hyperinsulinism). Particular attention is devoted to the role of mechanotransduction in beta-cell fate determination.
3) Iron and neurotransmitter transporters in the nervous system and peripheral organs. We are interested in understanding how these transporters work as molecules, what tasks they fulfill in cell physiology and whether their activity/expression is modified in neurodegenerative diseases.

Technologies

To achieve these goals, we use cellular (neuronal and beta cell lines and primary cultures) and small animal (mouse, zebrafish) models and we apply state-of-the-art techniques, including:

• Confocal Microscopy and Total Internal Reflection Fluorescence Microscopy (TIRFM) to study the events taking place at/or immediately; beneath the plasma membrane, i.e. protein/vesicle exo- or endo-cytosis, protein clustering;  
• Ion imaging and electrochemical techniques to evaluate the electrical activity of cells and the release of hormones and neurotransmitters
• Generation of genetically encoded sensors for in vivo imaging of plasma membrane dynamic events (synaptic vesicles and hormone granules exocytosis) and for in situ monitoring of ion and metabolite fluxes.
• 3D culture systems coupled to microfluidic for the control of differentiation and maturation processes in endocrine and neuronal cells in vitro. 
• Molecular biology techniques: RT-PCR, Site-directed mutagenesis, functional expression cloning, Northern blotting.
• Biochemistry techniques: Western blots; Immunoprecipitation; Generation, expression and purification of Recombinant proteins (GST/His/GTRAP-tagged); Affinity chromatography assays; ELISA assays.

Collaborators

Prof. Folli Franco, Dip di Scienze della Salute, UNIMI
Prof. Fiorina Paolo, Dip Sc Biomediche e Cliniche Sacco UNIMI e Boston Children’s Hospital, Harvard Medical Schoole
Prof.ssa Lenardi Cristina, Dip Fisica, UNIMI
Prof.ssa Tedeschi Gabriella, Dip Di Medicina Veterinaria, UNIMI
Dr. Miguzzi Alessandro, Dip di Chimica, UNIMI
Dr. Bertuzzi Federico, Ospedale Niguarda, Milano
Dr. Piccoli Giovanni, Università di Trento
Prof. La Rosa Stefano, Institut Universitaire de Pathologie, Lausanne
Prof. Florian Lang, Department of Physiology, University of Tübingen, Germany 

Selection of Publications

1. Galli A, Maffioli E, Sogne E, Moretti S, Di Cairano ES, Negri A, Nonnis S, Borghi F, Podestà A, Bertuzzi F, Milan P, Lenardi C, Tedeschi G, Perego C. (2018) Cluster-assembled zirconia substrates preserves long term human islet of Langerhans survival and differentiation. Nature Sci. Rep. Jul 2;8(1):9979. doi: 10.1038/s41598-018-28019-3
2. Perez Carrion MD, Marsicano S, Daniele F, Di Cairano ES, Marte A, Piovesan E, Von Zwiedorf F, Johannes X, Gloeckner C, Onofri F, Perego C, Piccoli G. (2017) The LRRK2 G2385R variant is a partial loss-of-function mutation and affects synaptic vesicles trafficking through altered protein interactions. Nature Sci. Rep. 7(1):5377. doi: 10.1038/s41598-017-05760-9
3. Di Cairano ES, Moretti S, Marciani P, Sacchi VF, Castagna M, Davalli A, Folli F, Perego C. (2016) Neurotransmitters and Neuropeptides: New Players in the Control of Islet of Langerhans' Cell Mass and Function. J Cell Physiol. 231(4):756-67. doi: 10.1002/jcp.25176.
4. Buracco S, Peracino B, Cinquetti R, Signoretto E, Vollero A, Imperiali F, Castagna M, Bossi E, Bozzaro S. Dictyostelium Nramp1, which is structurally and functionally similar to mammalian DMT1 transporter, mediates phagosomal iron efflux. J Cell Sci. 2015;128(17):3304-16. doi: 10.1242/jcs.173153
5. Di Cairano ES, Davalli AM, Perego L, Sala S, Sacchi VF, La Rosa S, Placidi C, Cappella C, Conti P, Centonze VE, Casiraghi F, Bertuzzi F, Folli F, and Perego C. (2011) The glial glutamate transporter 1 (GLT1) is expressed by pancreatic beta-cells and prevents glutamate-induced beta-cell death. J Biol Chem. 286 (16):14007-18.