Maria Vittoria Schiaffino
Location: DIBIT2 A2, Floor 4, Room 44
Research associate, Age related disease Unit
Mammalian cells contain a specific repertoire of membrane-bound organelles that are essential for their survival and role within the organism. The biogenesis, motility, signaling and intracellular connections of these organelles is required for their proper function and, when altered, can result in a variety of human diseases.
My research activity focuses on the mechanisms underlying these processes by studying the molecular pathogenesis of ocular albinism type 1, a genetic disorder characterized by visual impairment and by abnormalities of melanosomes, a special type of lysosome-related organelles, devoted to the synthesis and transport of melanin in pigment cells. In fact, loss-of-function of the ocular albinism gene OA1, encoding a unique G protein-coupled receptor localized to melanosomes, results in aberrant size, number and distribution of the organelles.
Recent findings of this Unit indicate that the proper biogenesis of melanosomes requires both tight juxtaposition with mitochondria, through fibrillar bridges resembling the protein tethers linking mitochondria and endoplasmic reticulum, and dedicated transcriptional programs, regulated by the microphthalmia family of transcription factors. A second line of research is focused on the cellular adaptations to nutrient restriction, including long-term epigenetic and transcriptional modifications.
2021-today Research asssociate, IRCCS Ospedale San Raffaele, Milan, Italy
2006-2021 Head of unit, IRCCS Ospedale San Raffaele, Milan, Italy
2001-2011 Appointed professor, San Raffaele Vita-Salute University, Milan, Italy
2000-2006 Senior researcher, IRCCS Ospedale San Raffaele, Milan, Italy.
1995-2000 Staff researcher, Telethon Institute of Genetics and Medicine (TIGEM), Milan, Italy
1993-1994 Research associate, Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas
1992-1993 Postdoctoral fellow, Department of Paediatrics, University of Padova Medical School, Italy
Daniele T and Schiaffino MV. Lipid transfer and metabolism across the endolysosomal-mitochondrial boundary. Biochim Biophys Acta. 2016 Aug;1861(8 Pt B):880-894.
Daniele T, Hurbain I, Vago R, Casari G, Raposo G, Tacchetti C and Schiaffino MV. Mitochondria and melanosomes establish physical contacts modulated by Mfn2 and involved in organelle biogenesis. Current Biology 2014 Feb 17;24(4):393-403.
Burgoyne T, Jolly R, Martin-Martin B, Seabra MC, Piccirillo R, Schiaffino MV, Futter CE. Expression of OA1 limits the fusion of a subset of MVBs with lysosomes; a mechanism likely involved in the initial biogenesis of melanosomes. Journal of Cell Science 2013 Nov 15;126(Pt 22):5143-52.
Palmisano I, Della Chiara G, D'Ambrosio RL, Huichalaf C, Brambilla P, Corbetta S, Riba M, Piccirillo R, Valente S, Casari G, Mai A, Boneschi FM, Gabellini D, Poli G, Schiaffino MV. Amino acid starvation induces reactivation of silenced transgenes and latent HIV-1 provirus via down-regulation of histone deacetylase 4 (HDAC4). Proc Natl Acad Sci U S A, 2012 Aug;109 (34) E2284-E2293.
Sitaram A, Piccirillo R, Palmisano I, Harper DC, Dell’Angelica EC, Schiaffino MV and Marks MS. Localization to mature melanosomes by virtue of cytoplasmic dileucine motifs is required for human OCA2 function. Molecular Biology of the Cell 2009 Mar;20(5):1464-77.
Palmisano I, Bagnato P, Palmigiano A, Innamorati G, Rotondo G, Altimare D, Venturi C, Sviderskaya EV, Piccirillo R, Coppola M, Marigo V, Incerti B, Ballabio A, Surace EM, Tacchetti C, Bennett DC, Schiaffino MV. The ocular albinism type 1 (OA1) protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells. Human Molecular Genetics 2008 Nov 15;17(22):3487-501
Piccirillo R, Palmisano I, Innamorati G, Bagnato P, Altimare D and Schiaffino MV. An unconventional dileucine-based motif and a novel cytosolic motif are required for the lysosomal and melanosomal targeting of OA1. Journal of Cell Science 2006 May 15;119(Pt 10):2003-14.
Innamorati G, Piccirillo R, Bagnato P, Palmisano I and Schiaffino MV. The melanosomal/lysosomal protein OA1 has properties of a G protein- coupled receptor. Pigment Cell Research 2006 May 15;119(Pt 10):2003-14.
Schiaffino MV, Dellambra E, Cortese K, Baschirotto C, Bondanza S, Clementi M, Nucci P, Ballabio A, Tacchetti C and De Luca M. Effective retroviral-mediated gene transfer in normal and mutant human melanocytes. Human Gene Therapy 2002 May 20;13(8):947-57.
Schiaffino MV, d’Addio M, Alloni A, Baschirotto C, Valetti C, Cortese K, Puri C. Bassi MT, Colla C, De Luca M, Tacchetti C and Ballabio A. Ocular Albinism: evidence for a defect in an intracellular signal transduction system. Nature Genetics 1999 Sep;23(1):108-12.
1996 PhD, Paediatric Development, University of Padova Medical School, Italy.
1991 M.D., magna cum laude, University of Padova Medical School, Italy.
1991 Italian Medical Licensure, Italian Ministry of Health, Italy.
1989-1991 Predoctoral fellow, Institute of Histology and Embryology, University of Padova Medical School, Italy.