The Cellular Neurochemistry Laboratory studies (1) the role of environmental factors in developmental disabilities, including autism spectrum disorder, (2) signal transduction and lipid abnormalities in autism, and (3) the regulation of amyloid beta-protein (Aβ) fibrillogenesis, which is a key event in amyloid plaque formation in the brains of adults with Down syndrome or Alzheimer disease. Recent data from several laboratories including IBR’s Morphometry Laboratory have also shown Aβ deposition in the brains of individuals with autism.
Our current projects are addressing the following:
- The role of environmental risk factors in developmental disabilities and behavioral abnormalities: We are studying the effects of methylmercury, bisphenol A, and alcohol alone and in combination on the development and behavior of larvae and flies. We are also analyzing gene expression, proteins, oxidative stress, mitochondrial functions, and lipidomics to understand the leading cause of behavioral and developmental disabilities caused by these environmental risk factors. In addition, we are studying whether mitochondria from the lymphoblasts of individuals with autism are more susceptible to damage caused by environmental risk factors than mitochondria from the lymphoblasts of control subjects.
- Control of hydrophobic domains formation of fibrillar Aβ and role of gelsolin in beta-amyloidosis: We are investigating the properties of abnormal folding of Aβ and identifying the compounds that can inhibit it. It is likely that these compounds can be used as therapeutic agents for diseases involving beta-amyloidosis. We have reported that expression of gelsolin, a beta-amyloid–, and an actin-binding protein, inhibits Aβ fibrillization and that its levels are increased in cells under oxidative stress. Cells under oxidative stress conditions are known to undergo apoptosis. We are studying the role of gelsolin in apoptosis.
- Protein phosphorylation and phosphoinositide metabolism in lymphoblasts and brain in autism: We are studying signal transduction and lipid metabolism in the lymphoblasts and post-mortem brain samples of individuals with autism as compared to normal subjects. Understanding the biochemical changes and signal transduction in the blood and brains of children with autism will assist in the diagnosis and/or therapeutic intervention of autism.