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Séminaire - Francesco PapaleoGenetics of Schizophrenia and Cognition

Abstract :

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 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. 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 also characterize neurobehavioral features of our genetically modified mice during critical developmental periods. In particular, we study ages in mice equivalent to human ages spanning from embryonic stages to adolescence/young adulthood (when schizophrenia often appear), up to adulthood. For direct translational purposes we also analyze specific genetic polymorphisms in patients with schizophrenia and matched controls. In these individuals we then examine psychopathological/neurocognitive profiles and structural/functional brain measures in collaboration with clinical research centers.

Selected publications

last publications

Papaleo F
, Burdick MC, Callicott JH, Weinberger DR. Epistatic interaction between COMT and DTNBP1 modulates prefrontal function in mice and in humans. Molecular Psychiatry. 2013 Oct 22. doi: 10.1038/mp.2013.133. [Epub ahead of print]. IF: 14.897.

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.

Scheggia D, Bebensee A, Weinberger DR, Papaleo F. The Ultimate Intra/Extradimensional Attentional Set-Shifting Task for Mice. Biological Psychiatry. 2013 

Scientific focus :

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”. 60000 €. 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”. 230000 €. 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”. 280000 €. September 2010- September 2014: Principal Investigator. Marie Curie FP7-Reintegration-Grants Call identifier: FP7-PEOPLE-2010-RG Grant N° 268247 – "SCHIZOGENES". 100000 €. August 2008-August 2010: Principal Investigator. NIMH Julius Axelrod Memorial Fellowship Training Award. Behavioral characterization of genetically modified mice for schizophrenia-associated susceptibility genes. 10% increase salary + 70000 $.

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.



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

December 2011- present: Tenured Researcher, Department of Pharmacological Sciences, University of Padova, Italy. June 2009- present: Team Leader, Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, Genova, Italy.

September 2005- August 2010: Post Doctoral Visiting Fellow, 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” (Dir.: Professor Guy Simonnet). Supervisors: Dr. Angelo Contarino and Professor Antoine Tabarin.