CURRICULUM

Nata a Vimercate (MB) il 5 Marzo 1983, ho conseguito il titolo di studio di Scuola Secondaria Superiore presso il Liceo Scientifico ‘A. Banfi’ (Vimercate, MB) nel 2002 e successivamente ho intrapreso il corso di Laurea Specialistica a Ciclo Unico in Medicina e Chirurgia presso l’Universita’ di Milano-Bicocca (Monza, MB), conclusosi nel 2008 con il massimo dei voti. Nel Luglio 2014, ho ottenuto il diploma della Scuola di Specialita’ in Ostetricia e Ginecologia, indirizzo di Medicina Materno-Fetale (Universita’ di Milano-Bicocca). Il mio interesse clinico e di ricerca e’ incentrato su quelle patologie specifiche della gravidanza con potenziali effetti negativi sullo sviluppo cerebrale fetale e neonatale, fra cui i disordini ipertensivi gestazionali e le infezioni perinatali. Al fine di approfondire la conoscenza dei meccanismi di danno cerebrale durante lo sviluppo intra-uterino e precoce post-natale, ho intrapreso il dottorato in Neuroscienze presso l’Università di Milano-Bicocca. Il mio progetto di ricerca ha come obiettivo definire gli effetti dell’infezione cerebrale da cytomegalovirus (CMV) durante fasi precoci di sviluppo e l’identificazione di potenziali nuovi approcci farmacologici per combattere, in modo efficace e sicuro, l’infezione virale cerebrale durante la gravidanza e in epoca neonatale.

PROGETTO DI RICERCA

Antiepileptic Drugs to Treat Cytomegalovirus Infection during Early Brain Development

• Curriculum: Neuroscienze Sperimentali
• Tutor: Dr. Andrea Alberto Lissoni (Università di Milano-Bicocca)
• Co-tutor: Prof. Michael J. Paidas (Yale University)
• Supervisore: Prof. Anthony van den Pol (Yale University)

Cytomegalovirus (CMV) is the most common infectious cause of brain defects and neurological dysfunction in developing human babies. Although drugs approved to treat CMV show some efficacy, their use is not recommended during pregnancy or in the neonatal period due to potential teratogenicity, acute and long-term toxicity, and carcinogenicity. The emergence of drug-resistant CMV strains also poses a challenge. No effective CMV vaccine is currently available. Therefore, novel anti-CMV strategies with alternative mechanisms of action and safer in vivo profiles are urgently needed. We recently reported that valnoctamide (VCD) and valpromide (VPD), neuroactive mood stabilizers with no known teratogenic activity, have anti-CMV potential in a murine model of severe perinatal infection, improving survival and postnatal growth. Since VCD displays a better in vivo profile and CMV-induced brain abnormalities represent the most severe complications following infection during early development, we further investigated whether the anti-CMV activity of VCD could be translated into a therapeutic effect to improve virally induced adverse neurological outcomes. Using multiple models of CMV infection in the developing mouse brain, we recently showed that VCD suppresses CMV by reducing virus available for entry into the brain, and by acting directly within the brain to block virus replication and dispersal. VCD restored timely acquisition of neurological milestones in neonatal mice and rescued long-term motor and behavioral outcomes in juvenile mice. CMV-mediated brain defects, including decreased brain size, cerebellar hypoplasia, and neuronal loss, were substantially attenuated by VCD. No adverse side effects on neurodevelopment of uninfected control mice receiving VCD were detected. Treatment of CMV infected human fetal astrocytes with VCD reduced both viral infectivity and replication by blocking viral particle attachment to the cell, a mechanism that differs from available anti-CMV drugs. These data suggest that VCD during critical periods of neurodevelopment can effectively suppress CMV replication in the brain and safely improve both immediate and long-term neurological outcomes.

ESPERIENZE ALL’ESTERO

Marzo 2015 – 2017: Dipartimento di Ostetricia, Ginecologia, e Scienze Riproduttive (Prof. Michael J. Paidas), e Dipartimento di Neurochirurgia (Prof. Anthony van den Pol), Universita’ di Yale – Scuola di Medicina, New Haven, CT, USA.

PUBBLICAZIONI E PARTECIPAZIONI A CONGRESSI RECENTI

Pubblicazioni

• Ornaghi S, Hsieh L, Bordey A, Vergani P, Paidas MJ, van den pol A. Valnoctamide inhibits cytomegalovirus infection in developing brain and attenuates neurobehavioral dysfunctions and brain abnormalities. Accepted for publication in Journal of Neuroscience on May 31st, 2017.
• van den Pol AN, Mao G, Yang Y, Ornaghi S, Davis JN. Zika Virus Targeting in the Developing Brain. J Neurosci. 2017 Feb 22;37(8):2161-2175.
• Ornaghi S, Davis JN, Gorres KL, Miller G, Paidas MJ, van den Pol AN. Mood stabilizers inhibit cytomegalovirus infection. Virology. 2016 Dec;499:121-135.
• Revello MG, Lazzarotto T, Guerra B, Spinillo A, Ferrazzi E, Kustermann A, Guaschino S, Vergani P, Todros T, Frusca T, Arossa A, Furione M, Rognoni V, Rizzo N, Gabrielli L, Klersy C, Gerna G; CHIP Study Group. A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. N Engl J Med. 2014 Apr 3;370(14):1316-26.

Congressi

• Ornaghi S, Hsieh L, Bordey A, Vergani P, Paidas MJ, van den Pol A. Valnoctamide treatment of cytomegalovirus infected newborn mice blocks brain infection and rescues aberrant postnatal neurobehavioral ontogeny. Presentazione orale, Society for Maternal and Fetal Medicine 37th Annual Pregnancy Meeting, Gennaio 2017, Las Vegas, NV, USA.
• Ornaghi S, Hsieh L, Bordey A, Vergani P, Paidas MJ, van den Pol A. Valnoctamide reverses cytomegalovirus-mediated brain injuries and neurological deficits in newborn mice. Presentazione poster, 6th International CMV Conference, Aprile 2017, Noordwjikerhout, The Netherlands.

ALTRE INFO

Per maggiori informazioni e per accedere alla lista completa delle pubblicazioni, visita Google Scholar.