Research Faculty

630 W. 168th St., Rm. 5-422,
New York, NY 10032

Phone: 212-342-5132
Fax: 212-342-4512
Education and Training
1998, Ph.D., Ohio State University
Umrao R. Monani, Ph.D
Associate Professor of Pathology and Cell Biology (in Neurology)
Research Summary

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.

Selected Publications

Tang, M., Gao, G., Rueda, C.B., Yu, H., Thiboxeaux, D.N., Awano, T., Engelstad, K. M., Quintero, M., Yang, H., Li, F., Li, H., Su, Q., Shetler, K.E., Jones, L., Seo, R., McConathy, J., Hillman, E., 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

Harding, B.N., Kariya, S., Monani, U.R., Chung, W.K., Benton, M., Yum, S.W., Tennekoon, G. and Finkel, R.S.. (2015) Spectrum of neuropathophysiology in spinal muscular atrophy type I. J. Neuropathol. Exp. Neurol. 74, 15-24

Kariya, S. Obis, T., Garone, C., Akay, T., 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. 124, 785-800

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

Kye, M-J., Niederst, E., Wertz, M.H., Gonçalves, I., Akten, B., Dover, K., Peters, M., Riessland, M., Neveu, P., Wirth, B., Kosik, K.S. Sardi, P., Monani, U.R., Passini, M. and Sahin, M. (2014) SMN regulates axonal local translation via miR-183/mTOR pathway. Hum. Mol. Genet. 23, 6318-6331

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

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

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

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.

Park, G-H., Kariya, S. and Monani, U.R. (2010) Spinal muscular atrophy: new and emerging insights from model mice. Curr. Neurol. Neurosci. Rep. 10, 108-117

Kariya, S., Mauricio, R., Dai, Y. and Monani, U.R. (2009) The neuroprotective factor Wld(s) fails to mitigate distal axonal and neuromuscular junction (NMJ) defects in mouse models of spinal muscular atrophy. Neurosci Lett. 449, 246-251

Kariya, S., Park, G-H., Maeno-Hikichi, Y., Leykekhman, O., Lutz, C., Arkovitz, M., Landmesser, L.T. and Monani, U.R. (2008) Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy. Hum. Mol. Genet. 17, 2552-2569

Gavrilina, T. O., McGovern, V. L., Workman, E., Crawford, T. O., Gogliotti, R. G., DiDonato, C. J., Monani, U.R., Morris, G. E., and Burghes, A. H. (2008). Neuronal SMN expression corrects spinal muscular atrophy in severe SMA mice while muscle-specific SMN expression has no phenotypic effect. Hum. Mol. Genet. 17, 1063-75

Monani, U.R. (2005) Spinal muscular atrophy: A deficiency of a ubiquitous protein; a disease of the motor neurons. Neuron 48, 885-895

McWhorter, M.L., Monani, U.R., Burghes, A.H.M. and Beattie, C.E. (2003) Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding. J. Cell Biol. 162, 919-931

Monani, U.R., Pastore, M.P., Gavrilina, T.O., Jablonka, S., Le, T.T., Andreassi, C., DiCocco, J.M., Lorson, C., Androphy, E.J., Sendtner, M., Podell, M. and Burghes, A.H.M. (2003) A transgene carrying an A2G missense mutation in the SMN gene modulates phenotypic severity in mice with severe spinal muscular atrophy. J. Cell Biol. 160, 41-52

Current Projects

Spinal muscular atrophy, AADC deficiency

Honors and Awards

1998: The Preston Fund Award for SMA research

2001: Development Grant - The Muscular Dystrophy Association

2004: American Academy of Neurology/SMA Foundation Young Investigator Award

2015: Sanofi Innovator Award
Committees , Council, and Professional Society Memberships

Society for Neuroscience

SMA, SMN, AADC, Genetics, Neurodegeneration

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