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Livio Pellizzoni, PhD

Academic Appointments

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

Control of the mRNA biogenesis pathway at multiple levels is critical for the proper temporal and spatial regulation of eukaryotic gene expression programs. Most post-transcriptional events of mRNA metabolism require ribonucleoprotein complexes (RNPs) and take place within higher-order macromolecular assemblies through elaborate and dynamic networks of RNA-protein and protein-protein interactions. Genetic mutations in both the RNA and protein components of this pathway that affect the efficiency and fidelity of these processes are often implicated in the etiology of inherited human neurodegenerative disorders.

Research in my laboratory aims at understanding the biogenesis and function of coding and non-coding RNPs as well as the role of RNA dysfunction in the pathophysiology of human motor neuron diseases. In particular, we study the molecular functions of the survival motor neuron (SMN) protein, which has emerged as a model molecular chaperone of RNPs. Reduced levels of SMN expression--due to homozygous deletions or mutations in the SMN1 gene--cause the inherited motor neuron disease spinal muscular atrophy (SMA), which is the leading genetic cause of death in infants. SMN is part of a macromolecular complex that functions in the biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs)— the essential components of the pre-mRNA splicing machinery--as well as probably other RNPs. The SMN complex acts to increase the efficiency and specificity of RNP assembly, and to provide an opportunity for RNA-protein interactions to be regulated in vivo. Importantly, in the spinal cord of mouse models of SMA, RNP assembly is defective and the extent of its reduction correlates with disease severity. Thus, a causative link between RNA dysfunction and SMA pathology is becoming increasingly evident. However, there is a need for a more detailed understanding of the neuronal functions of SMN, the molecular consequences of reduced SMN levels on pre-mRNA splicing and why alterations in these processes have particularly profound effects on motor neuron physiology.

We employ a variety of biochemical, molecular and cell-biological methods to investigate the normal functions of SMN in motor neurons and the pathological consequences of SMN deficiency in animal and cellular model systems. Beyond providing fundamental insights into RNA metabolism and motor neuron biology, these efforts will help to unravel the molecular defects of SMA and will help the design of appropriate therapeutic strategies.

Departmental Appointments

  • Department of Pathology & Cell Biology

Lab Locations

Honors & Awards

Honors

2002 EMBO Young Investigator

Research Interests

  • Neural Degeneration and Repair
  • Neurobiology of Disease
  • Synapses and Circuits
  • Stem Cell Biology
  • Cellular/Molecular/Developmental Neuroscience

NIH Grants

  • 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

    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

    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

    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

  • Tisdale, S. & Pellizzoni, L. (2015). Disease mechanisms and therapeutic approaches in spinal muscular atrophy. Journal of Neuroscience, 35(23), 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, 2013, 5(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(2), 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(2), 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(1), 126 138.
  • Workman, E., Saieva, L., Carrel, T.L., Crawford, T.O., Liu, D., Lutz, C., Beattie, C.E., Pellizzoni, L. & Burghes, A.H. (2009). A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice. Human Molecular Genetics, 18(12), 2215-2229.
  • Pellizzoni, L. (2007). Chaperoning ribonucleoprotein biogenesis in health and disease. EMBO Reports, 8(4), 340-345.
  • Gabanella, F., Butchbach, M.E.R., Saieva, L., Carissimi, C., Burghes, A.H. & Pellizzoni, L. (2007). Ribonucleoprotein assembly defects correlate with spinal muscular atrophy severity and preferentially affect a subset of spliceosomal snRNPs. PLoS ONE, 2(9), e921.
  • Gabanella, F., Carissimi, C., Usiello, A. & Pellizzoni, L. (2005). The activity of the Spinal Muscular Atrophy protein is regulated during development and cellular differentiation. Human Molecular Genetics, 14(23), 3629-3642.
  • Pellizzoni, L., Yong, J. & Dreyfuss, G. (2002). Essential role for the SMN complex in the specificity of snRNP assembly. Science, 298(5599), 1775-1779.

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