Umrao Monani, PhD

Profile Headshot

Overview

Academic Appointments

  • Darryl C. De Vivo Professor of Pediatric Neurology

Administrative Titles

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

Credentials & Experience

Education & Training

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

Honors & 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

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

Research Interests

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

Selected 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.