Mala V. Rao

Biosketch / Results /

Mala V. Rao, Ph.D.

Assistant Professor;
Department of Psychiatry

Contact Info

Address
140 Old Orangeburg Road
Orangeburg , NY 10962

845-398-5547
Mala.Rao@nyumc.org

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Education

— 7/95-7/99 Postdoctoral fellow in the laboratory of Dr. Don W. Cleveland, Department of Cell Biology, UCSD School of Medicine, PostDoctoral Training
— 12/91-12/92 Postdoctoral Fellow at the Pittsburgh Cancer Institute in Dr. Eli Gorelick's lab at Department of Pathology, PostDoctoral Training
— 8/86-11/91 Graduate student at the Department of Biochemistry in Prof. G. Padmanaban's lab, PostDoctoral Training
— Indian Institute of Science, Graduate Education
— 1/93-6/95 Postdoctoral Fellow in lab of late Prof. John P. Merlie, Department of Molecular Biology and Pharmacology, Washington University School of Medicine, PostDoctoral Training

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Research Summary

The major focus of my lab is to understand molecular cues that control the radia l 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 s tudied 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 increase s 100 fold, and large myelinated axons accumulate large numbers of neurofilament s (NFs). NFs are 10 nm filaments composed of NF-H (200 kd), NF-M (150 kd) and N F-L (68 kd) subunits. Genetic analysis has shown a direct correlation between t he number of filaments and axonal volume. Our transgenic mouse models have indi cated that subunit ratios play a critical role in controlling radial growth of a xons. Recent gene deletion analysis on individual subunits indicate that NF-L i s 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 tha t are responsible for controlling the radial growth of axons, a systematic domai n deletion approach is being used. We have successfully produced mice for carbox yl terminal deletions of NF-M and NF-H, and analyses of these mice are in progre ss. Approximately 2% of human ALS patients have mutations in the gene encoding for S OD1. A hallmark of ALS is neurofilament accumulation in cell bodies and proxima l 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 d isease onset and progression of motor neuron death is unknown. In order to addr ess 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.