 |
||||
|
Mala V. Rao, Ph.D. Assistant Professor Department of Psychiatry New York University School of Medicine (845)398-5547 rao@nki.rfmh.org The Rao Lab NYU Profile |
||||
|
Education
Postdoctoral Training
Awards
Research Interests
The major focus of my lab is to understand molecular cues that control the radial growth of axons and death of motor neurons. Radial growth of axons is studied in mice by ES cell mediated homologous recombination. Motor neurons disease is studied in mouse models of amyotrophic lateral sclerosis (ALS) in transgenic mice for neurofilaments and superoxide dismutase 1 (SOD1).
During development, axons undergo two major changes. First, the long, thin axons make growth cones and establish stable synapses. Second, axonal volume increases 100 fold, and large myelinated axons accumulate large numbers of neurofilaments (NFs). NFs are 10 nm filaments composed of NF-H (200 kd), NF-M (150 kd) and NF-L (68 kd) subunits. Genetic analysis has shown a direct correlation between the number of filaments and axonal volume. Our transgenic mouse models have indicated that subunit ratios play a critical role in controlling radial growth of axons. Recent gene deletion analysis on individual subunits indicate that NF-L is important for filament formation; NF-M is important for filament assembly and control of filament number. In order to identify the domains of NF subunits that are responsible for controlling the radial growth of axons, a systematic domain deletion approach is being used. We have successfully produced mice for carboxyl terminal deletions of NF-M and NF-H, and analyses of these mice are in progress. Approximately 2% of human ALS patients have mutations in the gene encoding for SOD1. A hallmark of ALS is neurofilament accumulation in cell bodies and proximal axons. Over 50 mutations in SOD1 have been identified in human ALS patients. A large number of mouse models exist for ALS. The role of each NF subunit in disease onset and progression of motor neuron death is unknown. In order to address this question, NF-H deleted and over-expressing mice are bred with SOD1 over-expressing mice and efforts are underway to characterize these mice. Results will indicate the role of NF-H in motor neuron-mediated cell death. Selected Publications Rao MV, Mohan PS, Kumar A, Montagna L, Campbell J, Yuan A, Espreafico EM, Julien JP, Nixon RA. The myosin Va head domain binds to the neurofilament-L rod and modulates local organelle content and distribution within axons. FASEB J (submitted). Yuan A, Sasaki T, Rao MV, Kumar A, Kanumuri V, Dunlop DS, Liem RK and Nixon RA. Neurofilaments form a highly stable stationary cytoskeleton after reaching a critical level in axons. J Neurosci. 2009;29:11316-11329. Garcia ML., Rao MV, Fujimoto J, Garcia VB, Shah SB, Crum J, Gotow T, Uchiyama Y, Ellisman M, Calcutt NA, Cleveland DW. Phosphorylation of highly conserved neurofilament medium KSP repeats is not required for myelin-dependent radial axonal growth. J Neurosci. 2009; 29:1277-84. Rao, M.V., Mohan, P.S., Peterhoff, C.M., Yang, D.S., Schmidt, S.D., Stavrides P.H., Campbell, J., Chen, Y., Jiang, Y., Paskevich, P.A., Cataldo, A.M., Haroutunian, V., and Nixon, R.A. Marked Calpastatin (CAST) depletion in Alzheimer’s disease accelerates cytoskeleton disruption and neurodegeneration: Neuroprotection by CAST overexpression. J. Neurosci. 2008; 28:12241-54. Yuan, A., Rao, M.V., Sasaki, T., Chen, Y., Kumar, A., Veeranna, Liem, R.K., Eyer, J., Julien, J.P., and Nixon, R.A. Alpha-internexin is structurally and functionally associated with the neurofilament triplet proteins in the mature CNS. J. Neurosci. 2006; 26:10006-19. Yuan, A., Nixon, R.A., and Rao, M.V. Deleting the phosphorylated tail domain of the neurofilament heavy subunit does not alter neurofilament transport rate in vivo. Neurosci. Lett. 2006; 393:264-8. Rao, M.V., and Ralph. A. Nixon. Defective neurofilament transport in mouse models of Amyotrophic lateral sclerosis. Neurochem. Res. 2003; 28:1041-47. Yuan, D., Rao, M.V., Kumar, A., Julien, J.P., and Nixon, R.A. Neurofilament transport in vivo minimally requires hetero-oligomer formation. J. Neurosci. 2003; 23:9452-9458. Rao, M.V., Campbell, J., Yuan, D., Kumar, A., Gotow, T., Uchiyama, Y., and Nixon, R.A. (2003). The neurofilament middle molecular weight subunit carboxyl terminal tail domain is essential for the radial growth and cytoskeletal architecture of axons but not for regulating neurofilament transport rate. Journal of Cell Biology 163:1021-1031. Yuan, D., Rao, M.V., Kumar, A., Julien, J.P., and Nixon, R.A. (2003). Neurofilament transport in vivo minimally requires hetero-oligomer formation. Journal of Neuroscience 23:9452-9458. Rao, M.V. and Nixon, R.A. (2003). Defective neurofilament transport in mouse models of amyotrophic lateral sclerosis: a review. Neurochemical Reseach 28:1041-1047.
Rao, M.V., Engle, L.J., Mohan, P.S., Yuan, A., Qiu, D., Cataldo, A., Hassinger, L., Jacobsen, S., Lee, V.M., Andreadis, A., Julien, J.P., Bridgman, P.C., Nixon, R.A. (2002) Myosin Va binding to neurofilaments is essential for correct myosin Va distribution and transport and neurofilament density. J. Cell Biol. 159:279-90. |
||||