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Umrao Monani, PhD

Academic Appointments

  • Associate Professor of Pathology and Cell Biology (in Neurology)

Current Administrative Positions

  • Member, Motor Neuron Center
  • Member, Columbia Translational Neuroscience Initiative
Umrao Monani, PhD

Our research interests center on two pediatric neurodegenerative diseases, Spinal Muscular Atrophy (SMA) and Aromatic L-Amino Acid (AADC) Deficiency.  SMA is a relatively common (carrier frequency of ~1 in 40) neuromuscular disorder caused by a deficiency of the SMN protein that results in spinal motor neuron degeneration.   AADC deficiency is a multi-symptomatic disease caused by the inability to synthesize normal levels of the neurotransmitters, serotonin and dopamine.   There is no effective cure for either disease.  Available treatments are palliative at best.

We use model mice to investigate the molecular and cellular basis of neurodegeneration in the two diseases.  Current projects utilize a combination of genetics, cell biology and functional assays to determine 1) the cellular site(s) of action of the SMN protein, 2) novel pathways linking protein deficiency in the two diseases to neurodegeneration and 3) the developmental requirements of AADC and SMN in health and disease.    It is expected that the results of these experiments will be instrumental in the design and implementation of safe and effective treatments for the disorders.  We are also interested in exploring the role of the SMN protein in other neurodegenerative disorders.  Establishing a link between SMN and these disorders is likely to shed light on more general mechanisms involved in the susceptibility and degeneration of neurons subjected to deficiencies in ubiquitously expressed proteins.

Departmental Appointments

  • Department of Pathology & Cell Biology

Education & Training

  • BS, Life Sciences, St. Xavier's College (India)
  • PhD, Molecular Genetics, Ohio State University College of Medicine

Lab Locations

Committees / Societies / Memberships

2010 - present - Member, Society for Neuroscience

Honors & Awards

  • 2000, Development Grant Award, Muscular Dystrophy Association of America
  • 2004, Young Investigator Award, American Academy of Neurology
  • 2015, Sanofi-Aventis Innovator Award

Research Interests

  • Pediatric Neurology
  • Neurobiology of Disease
  • Motor Neuron Disease
  • Synapses and Circuits

NIH Grants

  • GENE REPLETION IN GLUT1 DEFICIENCY SYNDROME (Private)

    Dec 15 2016 - Feb 14 2018

    EXPLORING THE POSTNATAL REQUIREMENT OF THE BRAIN FOR THE GLUT1 PROTEIN (Private)

    Jan 1 2017 - Dec 31 2017

    MEDIATORS OF THE SPINAL MUSCULAR ATROPHY NMJ PHENOTYPE (Private)

    May 9 2016 - Dec 8 2017

    DEFINING THE SPATIAL AND TEMPORAL REQUIREMENT OF THE GLUCOSE TRANSPORTER-1 IN GLUT1 DEFICIENCY SYNDROME (Private)

    Sep 1 2016 - Aug 31 2017

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

    Dec 1 2006 - May 31 2017

    AAV9-BASED TREATMENT FOR GLUT1 DS (Private)

    Dec 15 2015 - Dec 14 2016

    ELUCIDATING THE ROLE OF THE SMN PROTEIN IN THE DEVELOPING NEUROMUSCULAR SYSTEM (Private)

    Aug 1 2013 - Jul 31 2016

    GENE THERAPY OF GLUT1 DEFICIENCY (Private)

    Jan 1 2012 - May 31 2015

    IDENTIFYING SPINAL MUSCULAR ATROPHY MODIFIERS (Private)

    Oct 1 2012 - Sep 30 2014

    COLUMBIA SMA PROJECT: 4-AP AS A POTENTIAL SMA THERAPEUTIC AGENT AND BIOLOGICAL MECHANISMS OF ACTION (Federal Gov)

    Sep 1 2011 - Aug 31 2014

    THE PROTECTIVE EFFECTS OF SMN IN MOTOR NEURON DISEASE (Private)

    Feb 1 2011 - Sep 19 2013

    EXPLORING NOVEL GENETIC DETERMINANTS OF DISEASE SEVERITY IN SPINAL MUSCULAR ATROPHY MODEL MICE (Private)

    Sep 1 2011 - Aug 31 2013

    SPINAL MUSCULAR ATROPHY (SMA): DISEASE PHENOTYPE AND MECHANISMS (Federal Gov)

    Aug 1 2009 - Aug 31 2013

    MOUSE MODEL OF AROMATIC L AMINO ACID DECARBOXYLASE DEFICIENCY (Private)

    Aug 1 2012 - Jul 31 2013

    TOWARD A MOUSE MODEL OF AROMATIC L AMINO ACID DECARBOXYLASE DEFICIENCY (Private)

    Aug 1 2012 - Jul 31 2013

    TOWARD A MOUSE MODEL OF AROMATIC L-AMINO ACID DECARBOXYLASE DEFICIENCY (Private)

    Aug 1 2012 - Jul 31 2013

    DETERMINING DEVELOPMENTAL/TEMPORAL REQUIREMENTS OF THE SMN P ROTEIN (Private)

    Jan 1 2010 - Dec 31 2012

    INVESTIGATING THE TEMPORAL REQUIREMENTS OF THE SMN PROTEIN I N SMA (Private)

    Jan 1 2010 - Dec 31 2012

    INVESTIGATING THE TEMPORAL REQUIREMENTS OF THE SMN PROTEIN (Private)

    Mar 1 2010 - Feb 28 2012

    EFFECT OF THE SMN PROTEIN ON THE NEUROMUSCULAR SYSTEM OF SMA MICE (Private)

    Jan 1 2008 - Dec 31 2008

    EFFECT OF THE SMN PROTEIN ON THE NEUROMUSCULAR SYSTEM OF SMA MICE (Private)

    Jan 1 2008 - Dec 31 2008

    YOUNG INVESTIGATOR AWARD IN SPINAL MUSCULAR ATROPHY (Private)

    Jul 1 2004 - Dec 31 2008

Publications

2010 and later

  • Harding BN, Kariya S, Monani UR, Chung WK, Benton M, Yum SW, Tennekoon G, Finkel RS. (2015). Spectrum of neuropathophysiology in spinal muscular atrophy type I. J Neuropathol Exp Neurol. 74:15-24. doi: 10.1097/NEN.0000000000000144.
  • Kye MJ, Niederst ED, Wertz MH, Gonçalves Ido C, Akten B, Dover KZ, Peters M, Riessland M, Neveu P, Wirth B, Kosik KS, Sardi SP, Monani UR, Passini MA, Sahin M. (2014). SMN regulates axonal local translation via miR-183/mTOR pathway. Hum Mol Genet. 23:6318-6331. doi: 10.1093/hmg/ddu350.
  • Awano T, Kim JK, Monani UR. (2014). Spinal muscular atrophy: journeying from bench to bedside. Neurotherapeutics. 11:786-795. doi: 10.1007/s13311-014-0293-y. Review.
  • Monani UR, De Vivo DC. (2014). Neurodegeneration in spinal muscular atrophy: from disease phenotype and animal models to therapeutic strategies and beyond. Future Neurol. 9:49-65.
  • Kariya, S., Obis, T., Garone, T., Akay, A., Sera, F., Iwata, S., Homma, S. and Monani, U.R. (2014)  Requirement for enhanced Survival Motoneuron protein imposed during neuromuscular junction maturation. J. Clin. Invest. (in press).
  • Monani, U.R. and De Vivo, D.C. (2014) Neurodegeneration in spinal muscular atrophy: from disease phenotype and animal models to therapeutic strategies and beyond. Fut. Neurol. 9, 49-65.
  • Lee, J-H., Awano, T., Park, G-H. and Monani, U.R.  (2012) Limited phenotypic effects of selectively augmenting the SMN protein in the neurons of a mouse model of severe spinal muscular atrophy.  PLoS One 7(9):e46353.
  • Kariya, S., Jacquier, A., Re, D., Nelson, K., Przedborski, S. and Monani, U.R.  (2012) Mutant superoxide dismutase 1 (SOD-1), a cause of familial amyotrophic lateral sclerosis, disrupts the recruitment of SMN, the spinal muscular atrophy protein to nuclear Cajal bodies.  Hum. Mol. Genet. 21, 3421-3434.
  • Ruggiu, M., McGovern, V.L., Lotti, F., Saieva, L., Li, D.K., Kariya, S., Monani, U.R., Burghes, A.H.M. and Pellizzoni, L. (2012) A role for SMN exon 7 splicing in the selective vulnerability of motor neurons in spinal muscular atrophy Mol. Cell. Biol. 32, 126-138.
  • Lutz, C.M., Kariya, S., Patruni, S., Osborne, M.A., Liu, D., Henderson, C.E., Li, D.K., Pellizzoni, L., Rojas, J., Valenzuela, D.M., Murphy, A.J., Winberg, M.L. and Monani, U.R. (2011) Post-symptomatic restoration of SMN rescues the disease phenotype in a mouse model of severe spinal muscular atrophy. J. Clin. Invest. 121, 3029-3041.
  • Park, G-H., Maeno-Hikichi, Y., Awano, T., Landmesser, L.T. and Monani , U.R. (2010) Reduced SMN protein in motor neuronal progenitors functions cell autonomously to cause spinal muscular atrophy in model mice expressing the human centromeric (SMN2) gene. J. Neurosci. 30, 12005-12019.

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