Livio Pellizzoni, PhD

Academic Appointments

  • Associate Professor of Pathology & Cell Biology
Livio Pellizzoni, PhD

Livio Pellizzoni is an Associate Professor holding a joint appointment in the Departments of Pathology & Cell Biology and Neurology at the Columbia University Medical Center. He received his B.S. degree from the University of Rome La Sapienza and his Ph.D. degree from the University of Rome Tor Vergata. He trained at the University of Pennsylvania where he was an HHMI fellow. In 2002, he started his independent career at the Institute of Cell Biology of Rome and was the recipient of the EMBO Young Investigator award and the Telethon Career Award. He has been on the faculty of Columbia University since 2007. 

Email: lp2284@cumc.columbia.edu

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 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.

Departments and Divisions

  • Department of Pathology & Cell Biology

Languages Spoken

  • Italian

Education and Training

  • BS, MS, 1992 Biology, Universita degli Studi di Roma
  • PhD, 1995 Biotechnology, Universita degli Studi di Roma

Lab Locations

  • 630 West 168th Street

    630 West 168th Street
    P&S 5-421
    New York, NY 10032
    Phone:
    (212) 305-3046
    Email:
    lp2284@cumc.columbia.edu

Patents

  1. 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.
  2. 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.
  3. 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.
  4. 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.

Committees / Societies / Memberships

RNA Society

Society for Neuroscience (SFN)

American Society for Cell Biology (ASCB)

American Society for Microbiology (ASM)

Honors and Awards

2002 EMBO Young Investigator Award

2002 Telethon Career Award

Research Interests

  • Cellular/Molecular/Developmental Neuroscience
  • Neurodegeneration and repair
  • RNA-binding proteins and non-coding RNA regulatory networks in neurological disorders
  • Synapses and Circuits

NIH Grants

  • MECHANISMS AND THERAPEUTIC TARGETING OF MOTOR NEURON DEATH IN SMA (Federal Gov)

    Feb 1 2020 - Jan 31 2025

    ESSENTIAL ROLE OF STASIMON IN MOTOR CIRCUIT DEVELOPMENT AND DISEASE (Federal Gov)

    Dec 1 2019 - Nov 30 2024

    MECHANISMS OF SYNAPTIC LOSS BY THE CLASSICAL COMPLEMENT PATHWAY IN MOTOR CIRCUIT DEVELOPMENT AND DISEASE (Federal Gov)

    Sep 15 2018 - Jun 30 2023

    MECHANISMS OF CENTRAL SYNAPTIC DYSFUNCTION IN SMA (Federal Gov)

    Apr 1 2012 - Jun 30 2022

    RNA-MEDIATED MECHANISMS OF MOTOR SYSTEM DYSFUNCTION IN SPINAL MUSCULAR ATROPHY (Federal Gov)

    Jun 1 2017 - Feb 28 2022

    THE ROLE OF P38 MAPK ACTIVATION IN SPINAL MUSCULAR ATROPHY (Federal Gov)

    Apr 1 2017 - Mar 31 2020

    SMN DYSFUNCTION IN FUS-DEPENDENT ALS (Federal Gov)

    Aug 15 2016 - Jul 31 2019

    THE ROLE OF P38 MAPK ACTIVATION IN SPINAL MUSCULAR ATROPHY (Federal Gov)

    Apr 1 2017 - Mar 31 2019

    SMN DYSFUNCTION IN FUS-DEPENDENT ALS (Federal Gov)

    Aug 15 2016 - Jul 31 2018

    PHARMACOLOGICAL INHIBITION OF P38MAPK AS A CANDIDATE THERAPEUTIC APPROACH FOR SMA (Private)

    Jun 1 2016 - May 31 2018

    SPINAL MUSCULAR ATROPHY ASSOCIATION PROPOSAL (Private)

    Jan 1 2006 - Mar 31 2018

    ROLE OF DEFECTIVE U7 SNRNP BIOGENESIS IN SPINAL MUSCULAR ATROPHY (Private)

    Feb 1 2016 - Jan 31 2018

    NOVEL GENETIC DETERMINANTS OF THE NEUROMUSCULAR SMA PHENOTYPE (Federal Gov)

    Dec 1 2006 - May 31 2017

    NOVEL GENETIC DETERMINANTS OF THE NEUROMUSCULAR SMA PHENOTYPE (Federal Gov)

    Dec 1 2006 - May 31 2017

    SMALL CHEMICAL MODULATORS OF SMN BIOLOGY AS CANDIDATE THERAPEUTICS FOR SMA (Federal Gov)

    Mar 1 2014 - Feb 28 2017

    ROLE OF SMN IN CYTOPLASMIC MRNA REGULATION (Private)

    May 1 2016 - Oct 31 2016

    CELLULAR BASIS OF MOTOR CIRCUIT DYSFUNCTION INDUCED BY SMN DEFICIENCY (Private)

    Jul 1 2014 - Jun 30 2016

    SMN CONTROL OF SNRNP BIOGENESIS: ROLE IN RNA SPLICING AND MOTOR NEURON SURVIVAL (Federal Gov)

    Apr 15 2010 - Mar 31 2016

    A GENOME-WIDE PHENOTYPIC SCREEN FOR MODIFIERS OF SMN EXPRESSION AND FUNCTION (Federal Gov)

    Feb 1 2014 - Jan 31 2016

    A NOVEL SPINAL CIRCUIT INVOLVED IN LOCOMOTION (Federal Gov)

    Feb 15 2013 - Jan 31 2016

    A GENOME-WIDE PHENOTYPIC SCREEN FOR MODIFIERS OF SMN EXPRESSION AND FUNCTION (Federal Gov)

    Feb 1 2014 - Jan 31 2016

    EVALUATION OF CANDIDATE CHEMICAL MODIFIERS OF SMN BIOLOGY IN A MOUSE MODEL OF SMA (Private)

    May 1 2015 - Oct 31 2015

    MOLECULAR AND CELLULAR CHARACTERIZATION OF SMN-MEDIATED U7 SNRNP ASSEMBLY (Federal Gov)

    Jun 1 2012 - May 31 2015

    MOLECULAR AND CELLULAR CHARACTERIZATION OF SMN-MEDIATED U7 SNRNP ASSEMBLY (Federal Gov)

    Jun 1 2012 - May 31 2015

    THERAPY FOR SPINAL MUSCULAR ATROPHY (Federal Gov)

    Mar 20 2010 - Feb 8 2015

    ROLE OF STASIMON DYSFUNCTION IN SPINAL MUSCULAR ATROPHY (Federal Gov)

    Feb 1 2012 - Jan 31 2014

    COLUMBIA SMA PROJECT: IDENTIFICATION OF GENETIC MODIFIERS OF SMN EXPRESSION AND FUNCTION (Federal Gov)

    Sep 3 2010 - Oct 2 2013

    A FUNCTIONAL CELL-BASED SCREEN FOR POTENTIAL SMA THERAPEUTIC COMPOUNDS (Federal Gov)

    Jul 15 2010 - Jun 30 2013

    NONCODING RNA TARGETS OF THE SPINAL MUSCULAR ATROPHY PROTEIN (Federal Gov)

    Sep 1 2009 - Aug 31 2012

    REGULATION OF SMN FUNCTION IN RIBONUCLEOPROTEIN ASSEMBLY (Private)

    Jul 1 2009 - Jun 30 2012

Publications

  • 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, 24, 930-940.
  • 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.

For a complete list of publications, please visit PubMed.gov