Lisa Ellerby’s work is focused on “polyglutamine expansion disorders,” such as Huntington’s disease (HD), Kennedy’s disease, spinocerebellar ataxia and Machado- Joseph disease. Her goal is to understand the mechanisms that result in cell death in these diseases and identify new molecular targets for potential drug development. Lisa M. Ellerby, Ph.D., Associate Professor
Molecular and cellular mechanisms of polyglutamine diseases
Ellerby believes that identifying the toxic fragments which result from the cleavage of the Huntington protein is a critical step toward finding a cure for this rare, incurable, genetic disorder that causes the loss of neurons in certain parts of the brain. Huntington’s disease results in a loss of movement control, personality changes, dementia, and early death.
In order to identify new molecular targets for HD she has developed cellular models of HD. Using these models, she, in collaboration with Dr. Robert Hughes, has evaluated which genes in the druggable genome prevent HD toxicity when knocked down. Ellerby is also involved in the development of methods that attempt to stimulate nerve cell growth to replace those that have been lost in Huntington’s sufferers.
One of the exciting scientific developments during the past year was a study led by Dr. Ellerby, in collaboration with other scientists, which identified the role of toxic fragments which result from the cleavage of ataxin-7 (SCA7), a polyglutamate disease protein. The study was done in the spinocerebellar tract, which connects the spinal cord to the brain. She has found that mice genetically engineered to develop SCA7 generate these toxic fragments. If the SCA7 mice are made without the production of these toxic fragments the onset of the disease is delayed and they live double the lifespan of the mice with SCA7. She went on further to show the enzyme responsible for the production of these fragments is caspase-7, a protease that causes cell death. The use of caspase-7 inhibitors which block the production of toxic fragments may have therapeutic affects in SCA7.
