Laboratory of Transcriptional Profiling
Our laboratory focuses on the molecular underpinnings of Alzheimer’s Disease. We focus on a protein called tau that is found normally in neurons. But when the tau protein aggregates or clumps into neurofibrillary tangles, it disrupts the integrity of the cells. This tau pathology is one of the classic hallmarks of Alzheimer's disease.
In another set of studies we are examining every protein found in the brain using a method based on cutting edge microarray technology. We are studying abnormal expression of proteins in tissue from people at high risk for AD and people with AD. We hope to identify novel brain chemicals that are involved in the pathological processes that result in neurodegenerative disease like AD and also protective factors. This will help us identify brain chemicals that can become treatment targets for new drugs.
Our current work involves gene expression profiling approaches to Alzheimer's disease and cellular models of neurodegeneration. We have a collaboration with Terry Goldberg, PhD, also at the Center, on the study of post-mortem brain samples to look for regional differences in brain transcripts (i.e. brain chemicals) of people with genes that put them at risk for Alzheimer’s (apoE4 allele carriers) and other tissue from people who have no known genetic risk factors (non apoE4 allele carriers). These differences may help explain why people with this flavor of the apoE gene are at risk for late-onset Alzheimer’s. The post-mortem samples are from people who died of other causes, not Alzheimer’s, so we can isolate early changes in brain before disease. We are also using microarray studies to look at expression of the tau protein and secondary effects due to the isoforms. In molecular experiments in living cells, we are examining the effects of abnormal tau on different cell functions, and how different drugs may impact tau protein. Tau fills the tangles in the Alzheimer’s brain and understanding how and why tau is involved with the disease can help solve the puzzle of the mind-robbing disease and lead to ways to prevent and treat Alzheimer’s.
Lab Member
Name: Shufen Chen, MD
Position: Research Assistant
Research: Works with microarray technology in the study of the Molecular genetics of Alzheimer's disease.
E-mail: schen3@nshs.edu