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2007-A-026-FEL - Abstract

Grant Information

Grant
2007-A-026-FEL
Aging - Fellowship
Title
Analysis of Frontotemporal Dementia Genes in Drosophila
Investigator
Huidy Shu, MD, PhD
Institution
UCSF
Biochemistry and Biophysics
Funding Status
  • Completed
  • 3 years, $60,000 per year
  • 7/1/2007 to 6/30/2010

Abstract

2007-A-026-FEL - Abstract
Brief Summary
"Analysis of Frontotemporal Dementia Genes in Drosophila"

Frontotemporal dementia (FTD) is the most common member of a family of dementing illnesses characterized by focal degeneration of the frontal and temporal lobes of the brain. Patients with FTD differ from Alzheimer’s disease (AD) patients in that their presenting symptoms are usually behavioral changes or language dysfunction in the absence of significant memory impairment. Little is known about the molecular causes of FTD compared to AD. However, recent human genetic studies have isolated a number of genes that are mutated in rare families with hereditary FTD. One of these genes encodes Valosin-containing protein (VCP), an evolutionarily conserved protein that has a variety of roles within nerve cells, or neurons.

I am currently studying VCP in the fruit fly species Drosophila melanogaster because of the powerful methods available to study neuronal structure and function in Drosophila. I have genetically modified fruit flies to have too much and too little VCP activity, and I have genetically engineered fruit flies to carry a specific VCP mutation that causes FTD in humans. Using a variety of genetic, morphologic and physiologic techniques, I hope to discover the molecular mechanisms of neuronal dysfunction and degeneration caused by mutations in VCP. A detailed understanding of these mechanisms may help to facilitate the rational development of effective therapies for FTD.

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