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Francesco Papaleo

Senior Researcher Tenured - Principal Investigator

Research Line

Genetics of Cognition


IIT Central Research Labs Genova


Via Morego 30
+39 010 2896 786
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February 2014- present: Tenure Track II, Team Leader, Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, Genova, Italy.


January 2013- present: Adjunct Faculty Investigator, Lieber Institute for Brain Development. Baltimore, MD, USA.


December 2011- February 2014: Tenured Researcher, Department of Pharmacological Sciences, University of Padova, Italy.


June 2009- February 2014: Team Leader, Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, Genova, Italy.


September 2005- August 2010: Post DoctoralFellow, Clinical Brain Disorders Branch, National Institute of Mental Health, NIH, Bethesda, USA. Supervisors: Dr. Daniel R. Weinberger and Dr. Jacqueline N. Crawley.

January 2005- August 2005: “Assistant Associé”, University of Bordeaux 2, France, “Laboratoire Homéostasie-Allostasie-Pathologie”. Supervisors: Prof. Antoine Tabarin and Dr. Angelo Contarino.

July 2004- December 2004: Researcher, “Laboratoire Homéostasie-Allostasie-Pathologie”, University of Bordeaux, France. Supervisors: Prof. Antoine Tabarin and Dr. Angelo Contarino.


September 2003- July 2004: Researcher, INSERM Unit 588, “Laboratoire de Physiopathologie du Comportement”, Bordeaux, France. Supervisors: Dr. Pier Vincenzo Piazza and Dr. Angelo Contarino.


January 2002- March 2005: PhD Student in Pharmacology and Toxicology, University of Padova, Italy. Thesis title: Opposite roles for CRF/CRF1 receptor pathways in somatic and affective components of the opiate withdrawal syndrome. Supervisor: Dr. Angelo Contarino.


December 2000- November 2001: Pharmacist. S. Chiara pharmacy. Vicenza, Italy. Supervisor: Dr. Paolo Pretto.


October 1996- November 2001: Pharmacy graduate studies (110/110 cum Laude), University of Padova, Italy. Thesis title: Mice deficient for Corticotropin-releasing factor receptor 1 show physical but not affective signs of opiate withdrawal. Supervisors: Prof. Pietro Giusti and Dr. Angelo Contarino.



January 2014- December 2015: in charge of a work package. 2013 NARSAD Young Investigator grant. Title: “Indicated prevention with long-chain polyunsaturated omega-3 fatty acids in patients with 22q11 microdeletion syndrome genetically at high risk for psychosis: A randomised, double blind, placebo-controlled treatment trial”.

January 2013- December 2014: Principal Investigator. Roche Postdoc Fellowship Program; title: “D2L/S-dysbindin genetic interaction: towards early detection and personalized interventions for cognitive deficits and schizophrenia”.

January 2013- December 2015: Principal Investigator. Ricerca Finalizzata Giovani Ricercatori 2010 - Ministero Salute – project GR-2010-2315883, title: “Schizophrenia pathogenetic mechanisms associated to dysbindin dysfunctions in fly and mouse models”.

September 2010- September 2014: Principal Investigator. Marie Curie FP7-Reintegration-Grants Call identifier: FP7-PEOPLE-2010-RG Grant N° 268247 – "SCHIZOGENES".

August 2008-August 2010: Principal Investigator. NIMH Julius Axelrod Memorial Fellowship Training Award. Behavioral characterization of genetically modified mice for schizophrenia-associated susceptibility genes.


Genetics of Schizophrenia and Cognition

The etiology of neurodevelopmental behavioral disorders such as schizophrenia is complex and largely unknown, with both genetic and environmental contributing factors. While several potential schizophrenia-susceptibility genes have been identified, effect sizes are very small and replication is inconsistent, likely because of the complexity of human polymorphisms, genetic and clinical heterogeneity and the potential impact of gene-gene and gene-environment interactions. In this context, mutant mice bearing targeted mutations of schizophrenia-susceptibility genes are unique tools to elucidate the neurobiological basis of this devastating disorder.

Using genetically modified mice for genes relevant to schizophrenia, we will then employ a combined approach beginning at the behavioral level and culminating at the cellular and molecular levels. Cognitive abnormalities are core enduring symptoms in schizophrenia, dramatically contribute to poor functional outcomes in patients and currently represent a great “unmet therapeutic need”. We then mainly focus our work on behavioral cognitive analyses and relative neuronal correlates (e.g. in vivo electrophysiology, magnetic resonance imaging, microdialysis etc.).

New hope for preventing and curing schizophrenia-related symptoms and its cognitive deficits can come from early detection and early intervention. Thus, to develop effective tools for detecting high-risk individuals and prodromal stages we will also characterize neurobehavioral features of our genetically modified mice during critical developmental periods. Ontogenetic profiles will be analyzed at 1-24 postnatal days. At periods equivalent to adolescence/young adulthood in humans (when schizophrenia often appear), we will further assess 1) when the behavioral abnormalities identified in the adult ages first occur and 2) early neurochemical/synaptic dysfunctions within prefrontal cortex circuits.

For direct translational purposes we will also analyze specific genetic polymorphisms in patients with schizophrenia, 22q11 deletion syndrome and matched controls. In these individuals we will then examine psychopathological/neurocognitive profiles and structural/functional brain measures in collaboration with clinical research centers.

Current lab members:
Francesca Manago' (Post-doc)
Diego Scheggia (PhD student)
Huiping Huang (PhD student)
Sara Sannino (PhD student)

Selected Publications


  1. Sannino S, Gozzi A, Cerasa A, Piras F, Scheggia D, Manago F, Damiano M, Galbusera A, Erickson LC, Tonelli DDT, Bifone A, Tsaftaris SA, Caltagirone C, Weinberger DR, Spalletta G, Papaleo F. COMT Genetic Reduction Produces Sexually Divergent Effects on Cortical Anatomy and Working Memory in Mice and Humans. Cerebral Cortex 2014; doi: 10.1093/cercor/bhu053. IF: 6.828.

  2. Huang H, Michetti C, Busnelli M, Managò F, Sannino S, Scheggia D, Giancardo L, Sona D, Murino V, Chini B, Luisa Scattoni M, Papaleo F. Chronic and Acute Intranasal Oxytocin Produce Divergent Social Effects in Mice. Neuropsychopharmacology. 2014 Apr;39(5):1102-14. doi: 10.1038/npp.2013.310. Epub 2013 Nov 4. IF: 8.678.

  3. Papaleo F, Burdick MC, Callicott JH, Weinberger DR. Epistatic interaction between COMT and DTNBP1 modulates prefrontal function in mice and in humans. Molecular Psychiatry. 2014 Mar;19(3):311-6. doi: 10.1038/mp.2013.133. Epub 2013 Oct 22. IF: 14.897.

  4. Giancardo L, Sona D, Huang H, Sannino S, Managò F, Scheggia D, Papaleo F, Murino V. Automatic visual tracking and social behaviour analysis with multiple mice. PLoS One. 2013 Sep 16;8(9):e74557. doi: 10.1371/journal.pone.0074557. IF: 3.730.

  5. Scheggia D, Bebensee A, Weinberger DR, Papaleo F. The Ultimate Intra/Extradimensional Attentional Set-Shifting Task for Mice. Biological Psychiatry. 2013 Jun 27. doi:pii: S0006-3223(13)00475-7. 10.1016/j.biopsych.2013.05.021. [Epub ahead of print]. IF: 9.247.

  6. Carr GV, Jenkins KA, Weinberger DR, Papaleo F. Loss of dysbindin-1 in mice impairs reward-based operant learning by increasing impulsive and compulsive behavior. Behav Brain Res. 2013 Mar 15;241:173-84. doi: 10.1016/j.bbr.2012.12.021. Epub 2012 Dec 20. IF: 3.417.

  7. Papaleo F, Erickson L, Liu G, Chen J, Weinberger DR. Effects of sex and COMT genotype on environmentally modulated cognitive control in mice. Proc Natl Acad Sci U S A. 2012 Dec 4;109(49):20160-5. doi: 10.1073/pnas.1214397109. Epub 2012 Nov 19. IF: 9.737.

  8. Armando M, Saba R, Monducci E, Papaleo F, Dario C, Righetti V, Brandizzi M, Fiori P. Subtypes of psychotic-like experiences in a community sample of young adults: socio-demographic correlates and substance use. Rivista di Psichiatria, 2012, 47, 5: 424-431. IF: 0.235.

  9. Law AJ, Wang Y, Sei Y, O'Donnell P, Piantadosi P, Papaleo F, Straub RE, Huang W, Thomas CJ, Vakkalanka R, Besterman AD, Lipska BK, Hyde TM, Harrison PJ, Kleinman JE, Weinberger DR. Neuregulin 1-ErbB4-PI3K signaling in schizophrenia and phosphoinositide 3-kinase-p110δ inhibition as a potential therapeutic strategy. Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):12165-70. doi: 10.1073/pnas.1206118109. Epub 2012 Jun 11. IF: 9.737.

  10. Scheggia D, Sannino S, Scattoni ML, Papaleo F. COMT as a drug target for cognitive functions and dysfunctions. CNS & Neurological Disorders-Drug Targets. 2012 May;11(3):209-21. Review. IF: 3.810.

  11. Armando M, Papaleo F, Vicari S. COMT implication in cognitive and psychiatric symptoms in chromosome 22q11 microdeletion syndrome. CNS & Neurological Disorders-Drug Targets. 2012 May;11(3):273-81. Review. IF: 3.810.

  12. Papaleo F. COMT as a Drug Target for Nervous System Disorders. CNS & Neurological Disorders-Drug Targets. 2012 May;11(3):193-4. IF: 3.810.

  13. Ingallinesi M, Rouibi K, Le Moine C, Papaleo F, Contarino A. CRF2 receptor-deficiency eliminates opiate withdrawal distress without impairing stress-coping. Molecular Psychiatry. 2012 Dec;17(12):1283-94. doi: 10.1038/mp.2011.119. Epub 2011 Sep 27. IF: 14.897.

  14. Papaleo F, Silverman JL, Aney J, Tian Q, Barkan CL, Chadman KK, Crawley JN.Working memory deficits, increased anxiety-like traits and seizure susceptibility in BDNF overexpressing mice. Learning & Memory. 2011 Jul 26;18(8):534-44. Print 2011 Aug. IF: 4.219.

  15. Papaleo F, Lipska BK, Weinberger DR. Mouse models of genetic effects on cognition: Relevance to schizophrenia. Neuropharmacology. 2012 Mar;62(3):1204-20. Epub 2011 May 5. IF: 4.814.

  16. Papaleo F, Weinberger DR. Dysbindin and Schizophrenia: It’s dopamine and glutamate all over again. Biological Psychiatry. 2011 January 1; 69(1): 2-4. IF: 9.247.

  17. Papaleo F, Yang F, Garcia S, Chen J, Lu B, Crawley JN, Weinberger DR. Dysbindin-1 modulates prefrontal cortical activity and schizophrenia-like behaviors via dopamine/D2 pathways. Molecular Psychiatry 2012 Jan; 17(1):85-98. doi: 10.1038/mp.2010.106. Epub 2010 Oct 19. IF: 14.897.

  18. Ji Y, Yang F, Papaleo F, Wang HX, Gao WJ, Weinberger DR, Lu B. Role of dysbindin in dopamine receptor trafficking and cortical GABA function. Proc Natl Acad Sci. 2009 Nov 17; 106(46):19593-19598. Epub 2009 Nov 3. IF: 9.737.

  19. Papaleo F, Chen J, Weinberger DR. Animal models of genetic effects on cognition, in: The Genetics of Cognitive Neuroscience. MIT press. 2009. Chapter 3, pages 51-94.

  20. Papaleo F, Crawley JN, Song J, Lipska BK, Pickel J, Weinberger DR, Chen J. Genetic dissection of the role of Catechol-O-Methyltransferase in cognition and stress reactivity in mice. J. Neurosci. 2008 Aug 27; 28(35):8709-23. IF: 7.452.

  21. Papaleo F, Ghozland S, Ingallinesi M, Roberts AJ, Koob GF, Contarino A. Disruption of the CRF2 receptor pathway decreases the somatic expression of opiate withdrawal. Neuropsychopharmacology. 2008 Nov;33(12):2878-87. Epub 2008 Feb 20. IF: 7.991.

  22. Papaleo F, Kieffer BL, Tabarin A, Contarino A. Decreased motivation to eat in µ-opioid receptor-deficient mice. European Journal of Neuroscience. 2007 Jun; 25(11):3398-3405. IF: 3.631.

  23. Papaleo F, Kitchener P, Contarino A. Disruption of the CRF/CRF1 receptor stress system exacerbates the somatic signs of opiate withdrawal. Neuron. 2007 Feb 15;53(4):577-589. IF: 14.736.

  24. Papaleo F and Contarino A. Gender- and morphine dose-linked expression of spontaneous somatic opiate withdrawal in mice. Behavioural Brain Research. 2006 Jun 3; 170(1):110-8. IF: 3.417.

  25. Contarino A and Papaleo F. The corticotropin-releasing factor receptor-1 pathway mediates the negative affective states of opiate withdrawal. Proc Natl Acad Sci. 2005 Dec 20; 102(51):18649-18654. IF: 9.737.




Papaleo Google Scholar



November 2012:
Winter Conference on Brain Research Travel Fellowship Award.

May 2009: award as a Preceptor in the Howard Hughes Medical Institute Student Internship Program.

August 2008: two-year NIMH Julius Axelrod Memorial Fellowship Training Award.

May 2008: award as a Preceptor in the Howard Hughes Medical Institute Student Internship Program.

May 2007: mentor to prize winner of the American Academy of Neurology (AAN) Neuroscience Research Prize; Boston, annual meeting of the AAN.

September 2005- August 2010: fellowship, National Institute of Mental Health, NIH, USA.

January 2002- December 2004: doctoral fellowship, pharmacology program, University of Padova, Italy.

October 2003: scholarship from the Italian Society of Pharmacology.


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