Luca Colnaghi, PhD

Current Position

01.10.2021- Assistant Professor (Ricercatore RTDA), Physiology, Vita-Salute San Raffaele
University, Milan, Italy https://www.unisr.it/docenti/c/colnaghi-luca
01.02.2022- Project leader, Head of Laboratory of “Protein signaling in brain physiology and pathology” Division of Neuroscience, IRCCS San Raffaele Institute, Milan, Italy
https://research.hsr.it/en/divisions/neuroscience/luca-colnaghi.html

Education and training
2012-2015 Columbia University, NY, US Postdoctoral training in Neuroscience
2007-2011 NYU, New York, US Ph.D. in Cellular and Molecular Biology
2005-2007 University of Milan, Milan, Italy M.Sc. Biotechnology
2003-2005 University of Milan, Milan, Italy B.Sc. Biotechnology

Past positions and employment
2020-2021 Laboratory Head, Biological Regulation Unit, Department of Biochemistry, Mario
Negri Institute, Milan, Italy
2018-2019 Researcher, Department of Biochemistry, Mario Negri Institute, Milan, Italy

Peer-reviewed publications (in chronological order)
*First author; ^Corresponding author
1. Colnaghi L*, Villa G, Marcomini I, Poliani A, Fedeli M, Losi C, Rosa G, Manara DF. Knowledge,
Support, and Networking for Phelan-McDermid Syndrome: a study protocol. MethodsX, 2025.
https://doi.org/10.1016/j.mex.2025.103771.
2. Fiume S, Molinari F, Vai B, Poletti S, Citterio G, Fiumara F, Papin S, Paganetti P, Callari M and
Colnaghi L^. Prognostic and biological roles of Parkinson's disease genes in cancer. Movement
Disorders, 2025. doi: 10.1002/mds.30321.
3. Dell’Oca M, Boggio Bozzo S, Vaglietti S, Marchetti C, Di Luca C, Munarin P, Nicoli M, Indellicato
R, Ravanelli D, Falanga G, Iannielli A, Luoni M, Loffreda A, Berno V, Bianchini P, Sertic Sarah,
Conforti A, Rashidiani S, Aimaretti E, Collino M, Cecere I, Gallo A, Santoro F, Brancaccio D,
Rosso S, Di Nardo G, Pertusio R, Cesano F, Monje FJ, Ghirardi M, Roatta S, Colnaghi L^, and
Fiumara F^. NEDAMSS syndrome-related truncating and missense mutations cause aberrant
liquid-liquid phase separation of IRF2BPL triggering cellular and molecular disease
mechanisms. Nature Communications. 2025, in press Manuscript ID: NCOMMS-24-35906-T.
4. Callari M, Sola M, Magrin C, Rinaldi A, Bolis M, Paganetti P^, Colnaghi L^, Papin S. Cancerspecific
association between Tau (MAPT) and cellular pathways, clinical outcome, and drug
response. Scientific data. 2023 10(1), 637. doi:10.1038/s41597-023-02543-y.
5. Vaglietti S, Villeri V, Dell’Oca M, Marchetti C, Cesano F, Rizzo F, Miller D, LaPierre L, Pelassa I,
Monje F, Colnaghi L, Ghirardi M, Fiumara F. PolyQ length-based molecular encoding of
vocalization frequency in FOXP2. iScience. 2023 S2589-0042(23)02113
doi:10.1016/j.isci.2023.108036.
6. Priori EC, Musi CA, Giani A, Colnaghi L, Milic I, Devitt A, Borsello T, Repici M. JNK Activation
Correlates with Cognitive Impairment and Alteration of the Post-Synaptic Element in the
5xFAD AD Mouse Model. Cells. 2023 Mar 15;12(6):904. doi: 10.3390/cells12060904.
7. Elfers K, Menne L, Colnaghi L, Hoppe S, Mazzuoli-Weber G. Short- and Long-Term Effects of
Cocaine on Enteric Neuronal Functions. Cells. 2023 Feb 10;12(4):577.
doi:10.3390/cells12040577.
8.Gabbrielli S, Colnaghi L, Mazzuoli-Weber G, Redaelli ACL, Gautieri A. In Silico Analysis of Nanoplastics' and β-amyloid Fibrils' Interactions. Molecules. 2023 Jan 2;28(1):388. doi:10.3390/molecules28010388.
9. Natale C, Barzago MM, Colnaghi L, De Luigi A, Orsini F, Fioriti L, Diomede L. A Combined Cell-
Worm Approach to Search for Compounds Counteracting the Toxicity of Tau Oligomers In
Vivo. International Journal of Molecular Sciences. 2022 Sep 24;23(19):11277.
10. Windheimì J, Colombo L, Battajni NC, Russo L, Cagnotto A, Diomede L, Bigini P, Vismara E,
Fiumara F, Gabbrielli S, Gautieri A, Mazzuoli-Weber G, Salmona M, Colnaghi L^. Micro-and
Nanoplastics’ Effects on Protein Folding and Amyloidosis. International Journal of Molecular
Sciences 23 (18), 10329, 2022; https://doi.org/10.3390/ijms231810329
11. Musi AC, Colnaghi L, Giani A, Priori EC, Marchini G, Tironi M, Conci C, Cerullo G, Osellame R,
Raimondi MT, Remuzzi A, Borsello T. Effect of 3D Synthetic Microscaffold Nichoid on the
Morphology of Cultured Hippocampal Neurons and Astrocytes. Cells. 2022. 11(13), 2008; DOI:
10.3390/cells11132008
12. Musi CA, Marchini G, Giani A, Tomaselli G, Priori EC, Colnaghi L, Borsello T. Colocalization and
Interaction Study of Neuronal JNK3, JIP1, and β-Arrestin2 Together with PSD95. International
Journal of Molecular Sciences. 2022; 23(8):4113. DOI: 10.3390/ijms2308411
13. Marchetti C, Vaglietti S, Rizzo F, Di Nardo G, Colnaghi L, Ghirardi M, Fiumara F – Heptad
stereotypy, S/Q layering, and remote origin of the SARS-CoV-2 fusion core. Virus Evolution,
2021. DOI: 10.1093/ve/veab097
14. Conz A, Musi CA, Russo L, Borsello T, Colnaghi L^ – Super-resolution study of PIAS SUMO E3-
ligases in hippocampal and cortical neurons – European Journal of Histochemistry, 2021. DOI:
10.4081/ejh.2021.3241
15. Zanier ER, Barzago MM, Vegliante G, Romeo M, Bertani I, Natale C, Colnaghi L, Colombo L,
Russo L, Micotti E, Fioriti L, Chiesa R and Diomede L – C. elegans detects toxicity of traumatic
brain injury generated tau – Neurobiology of Disease, 2021. DOI: 10.1016/j.nbd.2021.105330
16. Colnaghi L*,^, Rondelli D, Muzi-Falconi M, Sertic S^ - Tau and DNA Damage in
Neurodegeneration. Brain Sciences, 2020. DOI: 10.3390/brainsci10120946
17. Russo L, Natale C, Conz A, Kelk J, Restelli E, Chiesa E, Salmona M, Fioriti L and Colnaghi L^ -
Super-resolution imaging of synaptic proteins in primary neurons. JoVE, 2020. DOI:
10.3791/61434
18. Colnaghi L*,^, Conz A, Russo L, Musi CA, Fioriti L, Borsello T and Salmona M - Neuronal
Localization of SENP Proteins with Super Resolution Microscopy. Brain Sciences, 2020. DOI:
10.3390/brainsci10110778
19. Drisaldi B*, Colnaghi L, ….., Kandel ER^ and Fioriti L^ - Cytoplasmic Polyadenylation Element
Binding proteins CPEB1 and CPEB3 regulate the translation of FosB and are required for
maintaining addiction-like behaviors induced by cocaine – Front. Cell. Neurosci, 2020. DOI:
10.3389/fncel.2020.00207.
20. Colnaghi L*,^, Russo L*, …., Fioriti L^ - Super Resolution Microscopy of SUMO proteins in
neurons – Front. Cell. Neurosci, 2019. DOI: 10.3389/fncel.2019.00486
21. Griffin Jr EA, Melas PA, Zhou1 R, Li Y, Mercado P, Kempadoo KA, Stephenson S, Colnaghi L,
Taylor K, Hu MC, Kandel ER and Kandel DB - Prior alcohol use enhances vulnerability to
compulsive cocaine self-administration by promoting degradation of HDAC4 and HDAC5.
Science Advances, 2017. DOI: 10.1126/sciadv.1701682
22. Colnaghi L*, Clemenza K, …., Levine AA - Social involvement modulates the response to novel
and adverse life events (stimuli) in mice. PLoS One, 2016. DOI: 10.1371/journal.pone.0163077
23. Fioriti L, Myers C, Huang YY, Li X, Trifilieff P, Colnaghi L, Drisaldi B and Kandel ER - The
Persistence of Memory in the Hippocampus Require Protein Synthesis mediated by the prionlike
Protein CPEB3. Neuron, 2015. DOI: 10.1016/j.neuron.2015.05.021
24. Stephan J, Fioriti L, Lamba N, Colnaghi L, Karl K, Derkatch I and Kandel ER - The CPEB3 protein
is a functional prion that interacts with the actin cytoskeleton. Cell Reports, 2015 June. DOI:
10.1016/j.celrep.2015.04.060
25. Drisaldi B*, Colnaghi L*, ….., Manley JL and Kandel ER- SUMOylation is an Inhibitory Constraint
that Regulates the Aggregation and Activity of the Functional Prion CPEB3. Cell Reports, 2015.
DOI: 10.1016/j.celrep.2015.04.061
26. Chen YH, Jones MJK, Yin Y, Crist SB, Colnaghi L, Sims III RJ, Rothenberg E, Jallepalli PV and
Huang TT - Phosphorylation-mediated monoubiquitination of FANCI uncouples dormant
origin firing from replication stress response. Mol Cell, 2015 June. DOI:
10.1016/j.molcel.2015.02.031
27. Huang YY, Levine A, Kandel DB, Yin D, Colnaghi L, Drisaldi B and Kandel ER - D1/D5 receptors
and histone deacetylation mediate the gateway effect of LTP in hippocampal dentate gyrus.
Learning and Memory, 2013. DOI: 10.1101/lm.032292.113
28. Piatkov KI, Colnaghi L, Bekes M, Varshavsky A and Huang TT – The auto-generated fragment
of the Usp1 deubiquitylase is a physiological substrate of the N-End rule pathway – Mol Cell,
2012. DOI: 10.1016/j.molcel.2012.10.012
29. Jones MJK*, Colnaghi L and Huang TT - Dysregulation of DNA polymerase κ recruitment to
replication forks results in genomic instability. EMBO, 2011. DOI: 10.1038/emboj.2011.457
30. Colnaghi L*, Jones MJK, …. Hanenberg H, Huang TT - Patient derived C-terminal mutation of
FANCI causes protein mislocalization and reveals putative EDGE motif function in DNA repair.
Blood, 2010. DOI: 10.1182/blood-2010-07-295758

Pre-print and under review articles
1. Colnaghi L^,*, Pagani S*, Paolini M, Lorenzi C, Spadini S, Finardi A, Colombo C, Zanardi R, Vai
B, Dugo M, Callari M, Furlan R, Benedetti F and Poletti S^. Peripheral transcriptomics reveal
inflammation-associated molecular signatures of treatment resistance in major depressive
disorder. 2025
2. Bettegazzi B, Indellicato R, Cattaneo S, Geusa M, Ravanelli D, Taverna S and Colnaghi L^. TAK-
981 inhibits the SUMOylation machinery to alter synaptic physiology. 2025
3. Ghandour T, Glausier JR, Asok A, Doyle MR, Campo P, Colnaghi L, Lewis DA, Kandel DB, Kandel
ER, de Guglielmo G, Huang SC, Melas PA. CircRNA hypomethylation in the human amygdala
implicates FKBP5 in alcohol use disorder. 2025, bioRxiv 2025.05.04.652083; doi:
https://doi.org/10.1101/2025.05.04.652083
4. Dell'Oca M, Boggio Bozzo S, Vaglietti S, Gurgone A, Cardinale V, Ragazzini G, Alessandrini A,
Colnaghi L, Ghirardi M, Giustetto M, Fiumara F. The CDKL5 kinase undergoes liquid-liquid
phase separation driven by a serine-rich C-terminal region and impaired by
neurodevelopmental disease-related truncations. 2024, bioRxiv 2024.11.18.624084; doi:
https://doi.org/10.1101/2024.11.18.624084

Clinical Studies
1. Role: PI 2025-2026 https://osf.io/p6snq
Title: “PMS Connect: Knowledge, Support, and Networking for Phelan-McDermid Syndrome”

Project Overview
The clinical trial aims to deepen the understanding of Phelan-McDermid Syndrome (PMS)
through an integrated approach that includes both a qualitative analysis of caregiver
experiences and the longitudinal collection of clinical and socio-demographic data from
individuals affected by PMS. Caregivers are recruited through the national patient association
AISPHEN. To achieve the project’s objectives, semi-structured interviews are conducted with
caregivers of individuals with PMS to explore their day-to-day experiences. Additionally, the
project includes a longitudinal study, with data collected from caregivers every six months
over the course of one year (T0, T1, T2). This includes clinical variables related to the person
with PMS, family context, and caregiver well-being. The longitudinal component allows the
creation of a disease registry, the first of its kind in Italy. Finally, a service map dedicated to
PMS is being developed and made available to families and healthcare professionals.