Rashmi Kothary

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Rashmi Kothary

Office: 613-737-8707
Work E-mail: rkothary@ohri.ca

Rashmi Kothary

Biography

Department of Cellular and Molecular Medicine, Faculty of Medicine; Ottawa Hospital Research Institute

Faculty of Medicine

Research Focus

To understand the basis of neurological and muscle diseases by examining how the biochemical structures of cells and their nuclei are related to these diseases. More specifically, this work concentrates on the following distinct issues: the role of a protein that is essential for interactions within cell membranes, the way in which the sheath protecting the body's nerve channels is maintained, and the mechanisms responsible for the loss of neurons caused by spinal muscular atrophy (SMA).

Research Relevance

The treatment of neuromuscular conditions such as spinal muscular atrophy and multiple sclerosis will only be possible with a clear understanding of the molecular events, which initiate and participate in the pathogenesis, that lead to these conditions. This is an important prelude to the development of therapeutic strategies designed to reduce or reverse the resulting damage.

Signals and sheaths: unraveling the mysteries of motor neurons

When the physical architecture of cells begins to break down, the function of cells within the body are compromised and a wide range of problems can arise. For example, signals controlling movements are transmitted along nerve tracts protected by a sheath of myelin, a specialized combination of proteins and lipids. If the cells that make up this sheath are lost, so too is the capability of the underlying nerves, resulting in the severe lack of coordination and muscle control associated with multiple sclerosis.

Rashmi Kothary and his team have been examining the specific molecular processes responsible for creation and maintenance of this myelin sheath. These researchers have been among the first to demonstrate the critical role of integrins, proteins that transmit signals from the extracellular milieu to the interior of cells, in generating and regenerating the myelin sheath. Their discovery has profound implications for the design of potential therapies for multiple sclerosis, which could be based on modulating the integrin signaling pathway to restore lost myelin.

This work has built on Kothary's ongoing exploration of dystonia musculorum, a hereditary neurodegenerative disorder characterized by the breakdown of intracellular scaffolds. By cloning the gene responsible for this ailment, he identified the encoded protein as part of a new class of proteins known as plakins, which play a key part in maintaining a cell's structural integrity. More recently, his laboratory has shown that this linker protein has an important role at the nuclear envelope.

Kothary has applied his expertise to another inherited disease, spinal muscular atrophy, which affects motor neurons in young infants and children. He is examining the function of a gene that appears to cause the breakdown in motor neurons that define this crippling condition. The ensuing insights are expected to point the way to promising therapies.

Awards and Accomplishments

  • Medical Research Council of Canada Scholarship
  • FRSQ Senior Researcher Award
  • Dr. J. David Grimes Career Achievement Award 
  • Excellence in Mentoring Award

 

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