Umrao Monani, PhD

Profile Headshot

Overview

Academic Appointments

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

Administrative Titles

  • Member, Motor Neuron Center
  • Member, Columbia Translational Neuroscience Initiative

Credentials & Experience

Education & Training

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

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

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.

Research Interests

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

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

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

Sep 1 2019 - Aug 31 2020

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

Sep 1 2018 - Aug 31 2020

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

May 1 2017 - Apr 30 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

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

Jan 1 2018 - Dec 31 2018

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

Dec 1 2006 - May 31 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

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

TRANSCRIPTIONAL DETERMINANTS OF MOTOR NEURON IDENTITY (Federal Gov)

Sep 15 2006 - Feb 28 2013

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

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

Jan 1 2008 - Jul 31 2011

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

Selected Publications

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.

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.