CURRICULUM

Born in Vimercate (Italy) on March 5th,1983, I graduated from Liceo Scientifico ‘A. Banfi’ (Vimercate, Italy) in 2002 and subsequently enrolled in the MD program at the University of Milan-Bicocca (Monza, Italy), completed in 2008 (110/110 summa cum laude). In July 2014, I obtained the Italian board in Obstetrics and Gynecology (track: Maternal-Fetal Medicine, University of Milan-Bicocca). Since the beginning of my medical career, my research has been focused on pregnancy-associated diseases with detrimental effects on fetal brain development, including hypertensive disorders and infections. To gain further insight into the potential mechanisms of early neurontogeny impairment induced by gestation-related events, in December 2014 I enrolled into the PhD program in Neuroscience of University of Milan-Bicocca. My doctoral work focuses on damage of the fetal brain induced by in-utero cytomegalovirus infection and the development of novel antivirals that can be safely used in pregnant mothers. This is a clinical area of highly significant unmet needs since no drugs are currently available to prevent or ameliorate viral-induced fetal brain abnormalities.

RESEARCH PROJECT

Antiepileptic Drugs to Treat Cytomegalovirus Infection during Early Brain Development

• Track: Experimental Neuroscience
• Tutor: Dr. Andrea Alberto Lissoni (University of Milan-Bicocca)
• Co-tutor: Prof. Michael J. Paidas (Yale University)
• Supervisor: 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.

ABROAD STAGE

March 2015 – 2017: Department of Obstetrics, Gynecology, and Reproductive Sciences (Prof. Michael J. Paidas), and Department of Neurosurgery (Prof. Anthony van den Pol), Yale University School of Medicine, New Haven, CT, USA.

RECENT PUBLICATIONS AND CONGRESSES

Publications

• 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.

Congresses

• 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. Oral presentation, Society for Maternal and Fetal Medicine 37th Annual Pregnancy Meeting, January 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. Poster presentation, 6th International CMV Conference, April 2017, Noordwjikerhout, The Netherlands.

FURTHER INFO

To get further details and the full pub list, go to the Google Scholar link.