Livio Pellizzoni, PhD
The development and function of neural circuits requires the precise spatial and temporal control of gene expression. Moreover, an increasing number of genetic mutations in ubiquitously expressed proteins that function in RNA regulation are linked to disorders of the nervous system. Research in our laboratory investigates the mechanisms by which RNA binding proteins (RBPs) and molecular chaperones that mediate their assembly into RNA-protein complexes (RNPs) regulate gene expression in neurons. The laboratory also focuses on the question of how general perturbations of RNA metabolism cause synaptic dysfunction and neuronal death in neurodegenerative diseases, including spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). In these studies, we employ cellular and animal models as well as a wide range of genomic, biochemical, molecular and imaging approaches. High-throughput screens are also used to discover chemical and genetic modifiers of disease pathways. On one hand, these efforts are designed to advance our knowledge of how RNA regulation contributes to neural circuit function. On the other, they aim to deconstruct disease mechanisms and identify potential therapeutic targets.
Current research interests focus on 1) the role of chaperone-mediated RNP assembly in development, disease and aging; 2) the identification and therapeutic targeting of upstream triggers and downstream effectors of motor dysfunction and neurodegeneration in SMA and ALS; 3) the characterization of disease-linked mutations in RBPs that disrupt neurodevelopment; and 4) the requirement of ER scramblases for the function of sensory-motor circuits.
- BS, University of Rome La Sapienza
- PhD, University of Rome Tor Vergata
- US Patent No: 6,646,113. G. Dreyfuss, U. Fischer, Q. Liu, B. Charroux, L. Pellizzoni. Nucleic acid molecule encoding human survival of motor neuron-interacting protein 1 (SIP1) deletion mutants. Assignee: The Trustees of the University of Pennsylvania. Issue Date: 11/11/2003. International Classifications: C12N; C07H; C07K.
- US Patent No: 7,459,309. G. Dreyfuss, U. Fischer, Q. Liu, B. Charroux, L. Pellizzoni. Isolated polypeptide deletion mutants of survival of motor neuron-interacting protein 1. Assignee: The Trustees of the University of Pennsylvania. Issue Date: 12/02/2008. International Classifications: C07H.
- US Patent Application No: 2009/0156,789. G. Dreyfuss, U. Fischer, Q. Liu, B. Charroux, L. Pellizzoni. Composition, Methods, and Kits Useful for the Diagnosis and Treatment of Spinal Muscular Atrophy. Publication Date: 06/18/2009.
- US Patent Application No: 61/712,220. B.D. McCabe, L. Pellizzoni. Diagnosis and Treatment of SMA and SMN Deficiency. Application Filed: 10/10/2013.
Society for Neuroscience (SFN)
American Society for Cell Biology (ASCB)
American Society for Microbiology (ASM)
1992 Laurea Summa Cum Laude, University of Rome La Sapienza
1995 Doctoral Degree in Biotechnology Summa Cum Laude, University of Rome Tor Vergata
2002 Telethon Career Award, Fondazione Telethon
2002 EMBO Young Investigator Award, European Molecular Biology Organization
- Van Alstyne, M., Tattoli, I., Delestree, N., Recinos, Y., Workman, E., Shihabuddin, L.S., Zhang, C., Mentis, G.Z. & Pellizzoni, L. (2021). Gain of toxic function by long-term AAV9-mediated SMN overexpression in the sensorimotor circuit. Nature Neuroscience, in press.
- Osman, E.Y., Van Alstyne, M., Yen, P.F., Lotti, F., Feng, Z., Ling, K.K.Y., Ko, C.P., Pellizzoni, L. & Lorson, C.L. (2020). Minor snRNA gene delivery improves the loss of proprioceptive synapses on SMA motor neurons. JCI Insight, 5, e130574.
- Simon, C.M., Van Alstyne, M., Lotti, F., Bianchetti, E., Tisdale, S., Watterson, D.M., Mentis, G.Z., & Pellizzoni, L. (2019). Stasimon contributes to the loss of sensory synapses and motor neuron death in a mouse model of spinal muscular atrophy. Cell Reports, 29, 3885-3901.
- Van Alstyne, M., Simon, C.M., Sardi, P.S, Shihabuddin, L., Mentis, G.Z., & Pellizzoni, L. (2018). Dysregulation of Mdm2 and Mdm4 alternative splicing underlies motor neuron death in spinal muscular atrophy. Genes & Development, 32, 1045-1059.
- Van Alstyne, M., Lotti, F., Dal Mas, A., Area-Gomez, E., & Pellizzoni L. (2018). Stasimon/Tmem41b localizes to mitochondria-associated ER membranes and is essential for mouse embryonic development. Biochemical and Biophysical Research Communications, 506, 463-470.
- Simon, C.M., Dai, Y., Van Alstyne, M., Koutsioumpa, C., Pagiazitis, J.G., Chalif, J.I., Wang, X., Rabinowitz, J.E., Henderson, C.E., Pellizzoni, L. & Mentis, G.Z. (2017). Converging mechanisms of p53 activation drive motor neuron degeneration in spinal muscular atrophy. Cell Reports, 21, 3767-3780.
- Simon, C.M., Janas, A.M., Lotti, F., Tapia, J.C., Pellizzoni, L. & G.Z. Mentis. (2016). A stem cell model of the motor circuit uncouples motor neuron death from hyperexcitability induced by SMN deficiency. Cell Reports, 16, 1416-1430.
- Tisdale, S. & Pellizzoni, L. (2015). Disease mechanisms and therapeutic approaches in spinal muscular atrophy. Journal of Neuroscience, 35, 8691– 8700.
- Li, D.K., Tisdale, S., Lotti, F. & Pellizzoni, L. (2014). SMN control of RNP assembly: from post-transcriptional gene regulation to motor neuron disease. Seminars in Cell & Developmental Biology, 32, 22-29.
- Tisdale, S., Lotti, F., Saieva, L., Van Meerbeke, J.P., Crawford T.O., Sumner, C.J., Mentis, G.Z. & Pellizzoni, L. (2013). SMN is essential for the biogenesis of U7 small nuclear ribonucleoprotein and 3’-end formation of histone mRNAs. Cell Reports, 5, 1187-1195.
- Lotti, F., Imlach, W.L., Saieva, L., Beck, E.S., Hao, L.T., Li, D.K., Jiao, W., Mentis, G.Z.M., Beattie, C.E., McCabe, B.D. & Pellizzoni, L. (2012). A SMN-dependent U12 splicing event essential for motor circuit function. Cell, 151, 440-454.
- Imlach, W.L., Beck, E.S., Choi, B.J., Lotti, F., Pellizzoni, L. & McCabe, B.D. (2012). SMN is required for sensory-motor circuit function in Drosophila. Cell, 151, 427-439.
- Ruggiu, M., McGovern, V.L., Lotti, F., Saieva, L., Li, D.K., Kariya, S., Monani, U.R., Burghes, A.H.M. & Pellizzoni, L. (2012). A role for SMN exon 7 splicing in the selective vulnerability of motor neurons in spinal muscular atrophy. Molecular and Cellular Biology, 32, 126-138.
- Pellizzoni, L. (2007). Chaperoning ribonucleoprotein biogenesis in health and disease. EMBO Reports, 8, 340-345.
- Pellizzoni, L., Yong, J. & Dreyfuss, G. (2002). Essential role for the SMN complex in the specificity of snRNP assembly. Science, 298, 1775-1779.
Complete lists of publications
- Neural Degeneration and Repair
- RNA binding proteins
- Molecular Mechanisms of Neurodegeneration
- Motor neuron biology and diseases
- RNA biology
- RNA processing