- Department of Pathology & Cell Biology
- Associate Professor of Pathology and Cell Biology (in Neurology)
Member, Motor Neuron CenterMember, Columbia Translational Neuroscience Initiative
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.
Education & Training
Primary Lab Locations
630 West 168th Street
New York, NY 10032
- (212) 342-5132
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
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.