CIVIERO LAURA

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Structure Department of Biology
Qualification Ricercatore a tempo determinato di tipo A
Scientific sector BIO/09 - PHYSIOLOGY
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Proposals for thesis
Project 1:
Identification of novel biomarkers in Parkinson's disease.

Project 2:
Understanding the physiological role of LRRK2 in astroglia

Project 3:
Glial phagocytic clearance: unraveling the molecular mechanisms

Curriculum Vitae
Positions and Employment

Present: Assistant Professor (RTDa, BIO/09), Department of Biology, University of Padua, Italy
September-October 2017: EMBO short-term fellow at University of Laval, Quebec
March-July 2017: Postdoctoral research fellow, Department of Biology, University of Padua, Italy
2014 - 2017: Senior post-doc, Department of Biology, University of Padova, Italy
2010 - 2014: Postdoctoral research fellow, Department of Biology, University of Padua, Italy
April-July 2013: EMBO short-term fellow, KULeuven, Belgium
March 2011: Visiting scientist, NIH, Bethesda, USA
2007-2009: PhD student in Biotechnology, Department of Biotechnology, University of Verona, Italy - Visiting PhD student, Imperial College, London

Awards and grants

2019: Symposium at ISN-ASN biennial meeting, Montreal, Canada. Role: organizer and chair
2018: Travel Grant, EMBO workshop, Lysosomes and metabolism, Naples, Italy
2017: Grant, Ricerca Finalizzata, Italian Ministery of Health (GR-2016-02363461): Role: PI
2017: EMBO Short-Term fellowship, CHUL, University of Laval, Canada
2017: Travel Grant, ISN-ESN biennial meeting, Paris, France
2016: Travel Grant, LRRK2: 10 years along the road to therapeutic intervention, Greenlands, UK
2016: Grant, MJFF (12080). Role: co-PI
2015: Grant, Senior fellowship, University of Padova. Role: PI
2013-2014: Telethon postdoctoral research fellowship
2013: Travel Grant, 3rd World Parkinson Congress, Montreal, Canada
2013: EMBO Short-Term fellowship, KULeuven, Leuven, Belgium
2012: Travel Grant, LRRK2 Function & Dysfunction, Egham, UK
2010-2012: MJFF postdoctoral research fellowship
2010: Travel Grant, 2nd World Parkinson Congress, Glasgow, UK
2010: PhD degree ‘Doctor Europaeus’, University of Verona and Imperial College

Oral presentations and invited seminars

2017: Invited seminar at CHUL, University of Laval, Quebec
2017: Selected oral presentation at Italian Society of Physiology Meeting, Pavia, Italy (Best Oral presentation Award)
2017: Selected oral presentation at Annual Meeting of Young Researchers, Italian Society of Physiology, Firenze, Italy
2016: Selected oral talk at Astrocyte School, Bertinoro, Itlay
2014: Selected oral presentation at Annual Meeting of Young Researchers, Italian Society of Physiology, Firenze, Italy
2014: Selected presentation at Society for Neuroscience Congress, Washington DC, US
2013: Selected presentation at Belgium Society of Neuroscience Meeting, Bruxelles, Belgium
2013: Invited seminar at Istituto Italiano di Tecnologia, Genova, Italy
2012: selected presentation at LRRK2 Function & Dysfunction, Egham, UK

Professional memberships

Member of Società Italiana di Fisiologia (from 2017)
Member of International Society of Neurochemistry (from 2017)
Member of Biochemical Society (from 2014)

Teaching activities

2017 - present: Anatomophysiology, degree in Optics and Optometry, University of Padova
2013: General Physiology, Laboratory, degree in Biology, University of Padova

Research areas
During my postdoctoral studies, I investigated the neuronal functions of Leucine-Rich Repeat Kinase 2 (LRRK2), a kinase involved in familiar forms of Parkinson’s disease (PD). Since 2010 I have contributed to the discovery and the validation both in vitro and in vivo of novel LRRK2-linked signaling pathways. My main achievements include the setting of an efficient purification protocol to obtain pure and active human LRRK2 from mammalian sources (Civiero et al, 2012). Recombinant LRRK2 has been employed for proteomic high-throughput approaches to unravel LRRK2 interactoma (Beilina et al, 2014; Civiero et al, 2015). Specifically, I identified p21-activated kinase 6 (PAK6) as a novel neuronal interactor of LRRK2 (Civiero et al, 2015). Supported by a senior fellowship awarded by the University of Padova, I started to explore the molecular mechanism and the functional significance of the LRRK2-PAK6 physical interaction in neuronal systems. PAKs are serine-threonine kinases implicated in different morphogenetic processes through remodeling of the actin cytoskeleton such as synapse formation and neuritogenesis (Civiero and Greggio, 2017). Using an in vivo neuromorphology assay, I showed that PAK6 is a positive regulator of neurite outgrowth and that LRRK2 is required for this function (Civiero et al, 2015). PAK6 is aberrantly activated in LRRK2-linked PD brains and mediates LRRK2 toxicity via the phosphorylation and the consequent release of the LRRK2-14-3-3 complex (Civiero et al, 2017). My studies reveal a novel regulatory mechanism in the brain mediated by two kinases, LRRK2 and PAK6, and provide a valuable platform to identify potential modulators in a pathological context. On this line, I contributed as co-principal investigator to a project entitled: ‘Targeting LRRK2:PAK6 pathway in Parkinson’s disease’ funded by the Michael J Fox Foundation for Parkinson Research. Recently, I was awarded as principal investigator a project entitled: ‘Novel therapeutic targets in Parkinson’s Disease’ funded by the Italian Ministry of Health that aims to identify aberrant activation of the PAK6-LRRK2-14-3-3 axis in human fluids as potential biomarkers in PD. Since 2017, I have been employed as assistant professor (RTDa) at University of Padova (settore scientifico disciplinare BIO/09) and I have expanded my research interests by establishing a line of research focused on the investigation of unexplored functions in astrocytes, fundamental cells in the regulation of neuronal physiology. To uncover novel physiological mechanisms in astrocytes and understand how astroglial dysfunction links to NDs, I am investigating the role of PD-linked, highly abundant proteins in these cells (e.g. LRRK2, GBA, ATP13A2).
My past and present research work is carried on in collaboration with international research groups where I am conducting in part my research activity supported by granted fellows. Biochemical characterization of LRRK2 and related proteins, with P. Lewis at Reading University and JM; Taymans at Jean-Pierre Aubert Research Center, Lille, France; in vivo validation of LRRK2 brain interactors, with E. Lobbestael at KU Leuven, Belgium; high-throughput approaches to the study of LRRK2 biology in neurons, with MR. Cookson at NIH, Bethesda, US; LRRK2 in astrocytes, with Carmignoto G. at University of Padova, Italy, Tremblay ME. at Laval University, Quebec, Iraci N. at University of Catania, Italy and, Hilfiker S. at CSIC-Universidad de Granada, Spain.

Publications
PAK6 Phosphorylates 14-3-3γ to Regulate Steady State Phosphorylation of LRRK2.
Civiero L*, Cogo S, Kiekens A, Morganti C, Tessari I, Lobbestael E, Baekelandt V, Taymans JM, Chartier-Harlin MC, Franchin C, Arrigoni G, Lewis PA, Piccoli G, Bubacco L, Cookson MR, Pinton P, Greggio E*. (*CA)
Front Mol Neurosci. 2017 Dec 14;10:417. doi: 10.3389/fnmol.2017.00417. eCollection 2017.

PAKs in the brain: Function and dysfunction.
Civiero L*, Greggio E*. (*CA)
Biochim Biophys Acta. 2018 Feb;1864(2):444-453. doi: 10.1016/j.bbadis.2017.11.005. Epub 2017 Nov 10. Review.

Molecular Insights and Functional Implication of LRRK2 Dimerization.
Civiero L, Russo I, Bubacco L, Greggio E.
Adv Neurobiol. 2017;14:107-121. doi: 10.1007/978-3-319-49969-7_6. Book Chapter.

Pharmacological LRRK2 kinase inhibition induces LRRK2 protein destabilization and proteasomal degradation.
Lobbestael E, Civiero L, De Wit T, Taymans JM, Greggio E, Baekelandt V.
Sci Rep. 2016 Sep 23;6:33897. doi: 10.1038/srep33897.

LRRK2 deficiency impacts ceramide metabolism in brain.
Ferrazza R, Cogo S, Melrose H, Bubacco L, Greggio E, Guella G, Civiero L*, Plotegher N*. (*CA)
Biochem Biophys Res Commun. 2016 Sep 23;478(3):1141-6. doi: 10.1016/j.bbrc.2016.08.082. Epub 2016 Aug 15.

LRRK2 phosphorylates pre-synaptic N-ethylmaleimide sensitive fusion (NSF) protein enhancing its ATPase activity and SNARE complex disassembling rate.
Belluzzi E, Gonnelli A, Cirnaru MD, Marte A, Plotegher N, Russo I, Civiero L, Cogo S, Carrion MP, Franchin C, Arrigoni G, Beltramini M, Bubacco L, Onofri F, Piccoli G, Greggio E.
Mol Neurodegener. 2016 Jan 13;11:1. doi: 10.1186/s13024-015-0066-z.

Leucine-rich repeat kinase 2 interacts with p21-activated kinase 6 to control neurite complexity in mammalian brain.
Civiero L, Cirnaru MD, Beilina A, Rodella U, Russo I, Belluzzi E, Lobbestael E, Reyniers L, Hondhamuni G, Lewis PA, Van den Haute C, Baekelandt V, Bandopadhyay R, Bubacco L, Piccoli G, Cookson MR, Taymans JM, Greggio E.
J Neurochem. 2015 Dec;135(6):1242-56. doi: 10.1111/jnc.13369. Epub 2015 Oct 19.

Genetic, structural, and molecular insights into the function of ras of complex proteins domains.
Civiero L, Dihanich S, Lewis PA, Greggio E.
Chem Biol. 2014 Jul 17;21(7):809-18. doi: 10.1016/j.chembiol.2014.05.010. Epub 2014 Jun 26. Review.

Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease.
Beilina A, Rudenko IN, Kaganovich A, Civiero L, Chau H, Kalia SK, Kalia LV, Lobbestael E, Chia R, Ndukwe K, Ding J, Nalls MA; International Parkinson’s Disease Genomics Consortium; North American Brain Expression Consortium, Olszewski M, Hauser DN, Kumaran R, Lozano AM, Baekelandt V, Greene LE, Taymans JM, Greggio E, Cookson MR.
Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2626-31. doi: 10.1073/pnas.1318306111. Epub 2014 Feb 7.

GTPase activity regulates kinase activity and cellular phenotypes of Parkinson's disease-associated LRRK2.
Biosa A, Trancikova A, Civiero L, Glauser L, Bubacco L, Greggio E, Moore DJ.
Hum Mol Genet. 2013 Mar 15;22(6):1140-56. doi: 10.1093/hmg/dds522. Epub 2012 Dec 13.

Biochemical characterization of highly purified leucine-rich repeat kinases 1 and 2 demonstrates formation of homodimers.
Civiero L, Vancraenenbroeck R, Belluzzi E, Beilina A, Lobbestael E, Reyniers L, Gao F, Micetic I, De Maeyer M, Bubacco L, Baekelandt V, Cookson MR, Greggio E, Taymans JM.
PLoS One. 2012;7(8):e43472. doi: 10.1371/journal.pone.0043472.

List of taught course units in A.Y. 2019/20
Degree course code (?) Degree course track Course unit code Course unit name Credits Year Period Lang. Teacher in charge
SC1168 COMMON SC02122203 8 1st Year (2019/20) Second
semester
ITA LAURA CIVIERO