Umrao Monani, PhD

Academic Appointments

  • Darryl C. De Vivo Professor of Pediatric Neurology

Current Administrative Positions

  • Member, Motor Neuron Center
  • Member, Columbia Translational Neuroscience Initiative
  • Affiliate Member - Zuckerman Institute
Umrao Monani, PhD

Email: um2105@cumc.columbia.edu

Our research centers on the basic biology of three relatively rare but devastating pediatric neurological diseases – with a view to developing the most effective treatments for infants and children afflicted with them.  One of these diseases, spinal muscular atrophy (SMA), primarily affects the neuromuscular system and is the result of reduced levels of the Survival Motor Neuron (SMN) protein.  The other two, Glucose Transporter-1 deficiency syndrome (Glut1 DS) and Aromatic L-Amino Acid (AADC) Decarboxylase deficiency, involve paucity of their namesake proteins and predominantly affect brain function.  The lab develops and employs mouse models of these diseases not only as a means to define how proteins underlying the three conditions govern neuronal health and viability but also as pre-clinical tools to test promising therapies.  While our immediate focus is on the three diseases we study, our research has broader implications and is expected to inform how the neuromuscular system and brain deteriorate during aging and in conditions such as Alzheimer’s disease, Parkinsonism and Diabetes.  Current projects utilize a combination of genetics, cell biology and functional assays to 1) define novel pathways linking protein deficiency in the three diseases we study to selective neuronal dysfunction, 2) develop new and improved therapies for individuals suffering from these and related diseases and 3) exploit findings from our studies on SMA, Glut1 DS and AADC deficiency to inform our general understanding of the cellular processes that maintain neurons and skeletal muscle in good health.  The lab welcomes inquiries from graduate students and postdoctoral scientists interested in careers devoted to the study of human genetics, the neurobiology of disease and the development of novel therapies for pediatric neurological conditions with unmet medical needs

Departmental Appointments

  • Department of Neurology
    Division of Child Neurology
    Division of Neuromuscular Medicine
  • Department of Pathology & Cell Biology

Education and Training

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

Lab Locations

  • 630 West 168th Street

    630 West 168th Street
    P&S 5-422
    New York, NY 10032
    Phone:
    (212) 342-5132
    Email:
    um2105@cumc.columbia.edu

Committees / Societies / Memberships

2010 - present - Member, Society for Neuroscience

Honors and Awards

  • 2000 - Development Grant Award, Muscular Dystrophy Association of America
  • 2004 - Young Investigator Award, American Academy of Neurology
  • 2015 - Sanofi-Aventis Innovator Award
  • 2020 - Endowed Chair, Pediatric Neurological Science
  • 2022 - Director, Colleen Giblin Laboratory for Research on Pediatric Neurological Disease

Research Interests

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

NIH Grants

  • SPINAL MUSCULAR ATROPHY: MECHANISMS & TREATMENT STRATEGIES. (Federal Gov)

    Dec 15 2018 - Nov 30 2022

    GENETIC SUPPRESSORS OF THE SMA PHENOTYPE (Private)

    Mar 1 2020 - Feb 28 2022

    DEFINING THE CELLULAR SITE OF ACTION OF THE GLUT1 PROTEIN IN GLUCOSE TRANSPORTER 1 DEFICIENCY SYNDROME (Private)

    Feb 1 2020 - Jan 31 2021

    RESTORING FUNCTION AT THE NMJ: A NOVEL MEANS TO TREAT SMA (Private)

    Sep 1 2018 - Aug 31 2020

    WHEN,DURING LIFE, IS THE GLUT1 PROTEIN MOST REQUIRED TO PREVENT DISEASE? (Private)

    Sep 1 2019 - Aug 31 2020

    DOES LOW SMN IN SATELLITE CELLS CONTRIBUTE TO MUSCLE PATHOLOGY AND THE OVERALL SMA PHENOTYPE? (Private)

    Apr 15 2019 - Apr 14 2020

    SMA MODULATORS AS A MEANS TO REVEALING DISEASE MECHANISMS (Private)

    Mar 1 2018 - Feb 28 2020

    THE SPINAL MUSCULAR ATROPHY NMJ PHENOTYPE: MECHANISMS AND MOLECULAR MEDIATORS (Federal Gov)

    May 1 2017 - Apr 30 2019

    EXPLORINGA NOVEL MEANS OF REGULATING GLUT1 EXPRESSION, AND ITS THERAPEUTIC IMPLICATIONS (Private)

    Jan 1 2018 - Dec 31 2018

    SPINAL MUSCULAR ATROPHY: MECHANISMS AND TREATMENT STRATEGIES. (Federal Gov)

    Dec 15 2017 - Dec 14 2018

    SPINAL MUSCULAR ATROPHY ASSOCIATION PROPOSAL (Private)

    Jan 1 2006 - Mar 31 2018

    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

    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

    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

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

    Aug 1 2009 - Aug 31 2013

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

    Sep 1 2011 - Aug 31 2013

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

    Aug 1 2012 - Jul 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

    TRANSCRIPTIONAL DETERMINANTS OF MOTOR NEURON IDENTITY (Federal Gov)

    Sep 15 2006 - Feb 28 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 (Private)

    Mar 1 2010 - Feb 28 2012

    COLUMBIA UNIVERSITY SPINAL MUSCULAR ATROPHY (SMA) RESEARCH P ROGRAM (Federal Gov)

    Jan 1 2008 - Jul 31 2011

    YOUNG INVESTIGATOR AWARD IN SPINAL MUSCULAR ATROPHY (Private)

    Jul 1 2004 - Dec 31 2008

    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

Publications

  • Tang, M., Park, S. H., Petri, S., Yu, H., Rueda, C. B., Abel, E. D., Kim, C. Y., Hillman, E. M., Li, F., Lee, Y., Ding, L., Jagadish, S., Frankel, W. N., De Vivo, D. C., & Monani, U. R. (2021). An early endothelial cell-specific requirement for Glut1 is revealed in Glut1 deficiency syndrome model mice. JCI insight, 6, e145789.
  • Kim, J-K., Jha, N.N., Feng, Z., Faleiro, M.R., Chiriboga, C.A., Wei-Lapierre, L., Dirksen, R.T., Ko, C-P., and Monani, U.R. (2020) Muscle-specific SMN reduction reveals motor neuron-independent disease in spinal muscular atrophy models. J. Clin. Invest. 130, 1271-1287.
  • Tang, M., Park, S.H., De Vivo, D.C. and Monani, U.R. (2019) Therapeutic strategies for Glucose Transporter-1 deficiency syndrome. Ann. Clin. Transl. Neurol. doi: 10.1002/acn3.5088.
  • Tang, M., Gao, G., Rueda, C.B., Yu, H., Thibodeaux, D.N., Awano, T., Engelstad, K.M., Sanchez-Quintero, M-J., Yang, H., Li, F., Li, H., Shetler, K.E., Jones, L., Seo, R., McConathy, J., Hillman, E.H., Noebels, J.L., De Vivo, D.C. and Monani, U.R. (2017) Brain microvasculature defects and Glut1-deficiency syndrome averted by early repletion of the Glucose Transporter-1 protein. Nat. Commun. 8, 14152 doi: 10.1038/ncomms14152.
  • Kim, J-K., Caine, C., Awano, T., Herbst, R. and Monani, U.R. (2017) Motor neuronal repletion of the NMJ organizer, Agrin, modulates the severity of the spinal muscular atrophy disease phenotype in model mice. Hum. Mol. Genet. 26, 2377-2385
  • Caine, C., Shohat, M., Kim, J-K., Nakanishi, K., Homma, S., Mosharov, E. V., Sulzer, D. and Monani, U.R. (2017) A pathogenic S250F missense mutation results in a mouse model of mild aromatic L-amino acid decarboxylase (AADC) deficiency. Hum. Mol. Genet. 26, 4406-4415
  • Kim, J-K. and Monani, U.R. (2018) Augmenting the SMN protein to treat infantile spinal muscular atrophy. Neuron doi: 10.1016/j.neuron.2018.02.009
  • 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.
  • 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.
  • 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.

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