Chang-En Yu, Ph.D.
Research Associate Professor
Research Interest: Dr. Yu’s research focus is on the molecular genetics of neurodegenerative and psychiatric disorders, which include Alzheimer’s disease (AD), frontotemporal dementia (FTD), Schizophrenia and Autism. The short-term goal is to identify the causative genes and better understand the molecular mechanism of these disorders. The long-term goal is to prevent and treat these disorders. Based on Dr. Yu’s apolipoprotein E gene (APOE) haplotypes study, he has identified a genomic region in the TOMM40 gene that showed very strong genetic association with AD. This association has been confirmed in three independent clinical AD case-control samples. This region is located roughly 15 Kb upstream of APOE gene and spans the N-terminal portion of the Tom40 protein. The Tom40 protein is a mitochondrial outer membrane pore protein, which is responsible for importing proteins into the mitochondria. Genetic markers within this region showed strong linkage disequilibrium (LD) with the e4 risk allele of the APOE gene, while multiple recombination hot spots were clearly present between these two loci. Therefore, the strong LD between APOE e4 risk allele and TOMM40 raises the possibility that part of the risk to AD commonly ascribed to e4 is actually due to variation in the TOMM40 gene and the Tom40 protein. Because evidences from other genetic studies have suggested that mitochondrial abnormalities and oxidative stress play a key role in AD risk; therefore, Dr. Yu has extended his study into functional assays to assess the effect of TOMM40 gene and its protein product on the risk of AD. In addition, a candidate region for Late-Onset Alzheimer’s Disease (LOAD) has been located on the short arm of chromosome 19 by linkage analysis. Dr. Yu has applied the whole candidate region association study to identified potential loci for LOAD in this region; and three loci have shown positive association with LOAD after validation analyses. Currently, rigorous tests are underway to identify the AD-causative genetic changes among these loci. Candidate gene identified from this study will have significant impact on Alzheimer’s disease (AD) and human health. It will provide further information to study molecular mechanism of AD and other complex neurodegenerative disorders.
Education and Training:
College: 1982, National Taiwan University, Taipei, Taiwan
Graduate School: Ph.D., 1990, Microbiology and Immunology, University of Oklahoma, Health Sciences Center
Postdoctoral Fellowship: 1990-1991, Microbiology and Immunology, University of Oklahoma, Health Sciences Center
Postdoctoral Fellowship: 1992-1995, Neurology, University of Washington
Postdoctoral Fellowship: 1995-1997, Geriatric Research Education and Clinical Center, VA puget Sound Health Care System, Seattle, WA
Publications: Go to PubMed.
Research Location Information: VAPSHCS
Seattle VA Puget Sound Health Care System
1660 S. Columbian Way
Seattle, WA 98108
Phone Number: (206)764-2863
Fax Number: (206)764-2569