Motor Neuron Center
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RESEARCH THEME: Spinal muscular atrophy - translating basic findings into a potential treatment
My research interests focus on motor neuron diseases in general and spinal muscular atrophy (SMA) in particular. SMA is a debilitating neuromuscular disease that primarily affects children. It is the leading genetic cause of mortality in infants and toddlers. SMA is caused by a deficiency of the survival motor neuron (SMN) protein due to mutations in the SMN1 gene. A copy gene, SMN2, modifies the severity of the disease, but does not produce sufficient SMN protein to fully compensate for mutations in SMN1.

To better understand the biology of SMA, I was primarily responsible for determining the key difference between the two SMN genes that explains why SMN1 is the SMA gene. This data was subsequently used to generate a series of mouse models of SMA that span the range of disease phenotypes seen in humans. The mice have provided us with invaluable information about the pathogenesis of the disease. In addition, they will play a key role in serving as tools to translate basic findings about SMA into a potential treatment for affected individuals.

Current projects in my laboratory focus on 1) collaborating with Dr. C. Henderson in using the SMA mice to determine why the motor neurons are so profoundly affected in the disease, 2) defining pathways that lead from a deficiency of the SMN protein to motor neuron death, and 3) using the data thus generated to identify new points of therapeutic intervention that will alleviate disease symptoms and serve to treat affected mice and eventually human patients.

BACKGROUND AND EDUCATION: Dr. Umrao R. Monani is an assistant professor of Neurology at the Columbia University Medical Center. He received his B.Sc. in the Life Sciences from St. Xavier's College, Bombay where he became interested in the genetics of human disease. He obtained a Ph.D. from the Department of Molecular Genetics at the Ohio State University. He stayed on at OSU to do his postdoctoral fellowship in the Department of Neurology under Arthur Burghes. During his fellowship, he was awarded a Development Grant from the Muscular Dystrophy Association and began working on the motor neuron disease, spinal muscular atrophy. His key work included defining the critical difference between the SMN1 and SMN2 genes and using it as a basis to generate a number of mouse models of SMA. He briefly worked in the biotechnology sector hoping to apply protein transduction technology to treat neurodegenerative diseases. In 2004, he won an American Academy of Neurology/SMA Foundation Young Investigator Award, returning to academia to be on faculty of the Department of Neurology at Columbia University.

EDUCATION AND TRAINING:

1990 B.Sc., St. Xavier's College, Bombay University
1998 Ph.D., Dept. of Molecular Genetics, The Ohio State University
1998-2003 Postdoctoral Fellowship, Dept. of Neurology, The Ohio State University
2003-2004 Research Scientist, Ansata Therapeutics Inc., La Jolla, CA
2004- Assistant Professor of Neurology, Columbia University

HONORS AND AWARDS:

1990 B.Sc., First Class, St. Xavier's College, Bombay University
1991 J.N. Tata Scholarship for the higher education of Indians
1996 Graduate Student Alumni Research Award, Member Sigma Xi
2000 Development Grant, The Muscular Dystrophy Association
2004 American Academy of Neurology/SMA Foundation Young Investigator Award

SELECTED PUBLICATIONS:
  • Monani, U.R., Sendtner, M., Coovert, D.D., Parsons, D.W., Andreassi, C., Le, T.T., Jablonka, S., Schrank, B., Rossol, W., Prior, T.W., Morris, G.E. and Burghes, A.H.M. (2000) The human centromeric survival motor neuron gene (SMN2) rescues embryonic lethality in Smn-/- mice and results in a mouse with spinal muscular atrophy. Hum. Mol. Genet., 9, 333-339.
  • 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 Biology 160, 41-52
  • 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 Biology 162, 919-931
  • Le, T.T., Pham, L.T., Butchbach, M.E., Zhang, H.L., Monani, U.R., Coovert, D.D., Gavrilina, T.O., Xing, L., Bassell, G.J. and Burghes, A.H. (2005) SMN Delta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN. Hum. Mol. Genet. 14, 845-857.
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