Ta Yuan Chang, PhD
Professor of Biochemistry & Cell Biology
Biochemistry & Cell Biology
National Taiwan University, Chemistry B.S., 1967
University of North Carolina, Chapel Hill, Biochemistry, Ph.D., 1973
Washington University School of Medicine, St. Louis, Biochemistry, Postdoc., 1973-76
Molecular and Cellular Biology Graduate Programs
Dartmouth Medical School
Department of Biochemistry
Hanover NH 03755
Acyl-Coenzyme A:cholesterol acyltransferase 1(ACAT1) is an enzyme responsible for intracellular cholesterol esterification and storage. It is a membrane bound protein located at the endoplasmic reticulum, and plays important roles in health and in diseases. Our laboratory identified the ACAT1 gene. We are conducting structure- function analysis of ACAT1 in vitro, and taking mouse genetic approaches to determine the pathophysiological role of ACAT1 in Alzheimer’s disease, in atherosclerosis, and in diet-induced obesity. In addition, this lab has been involved in using mutant cell lines to dissect discrete steps in intracellular cholesterol trafficking.
Yamauchi, Y., N. Iwamoto, M. A. Rogers, S. Abe-Dohmae, T. Fujimoto, C. C. Chang, M. Ishigami, T. Kishimoto, T. Kobayashi, K. Ueda, K. Furukawa, T. Y. Chang, and S. Yokoyama. 2015. Deficiency in the lipid exporter ABCA1 impairs retrograde sterol movement and disrupts sterol sensing at the endoplasmic reticulum. The Journal of biological chemistry 290: 23464-23477.
Shibuya, Y., Z. Niu, E. Y. Bryleva, B. T. Harris, S. R. Murphy, A. Kheirollah, Z. D. Bowen, C. C. Chang, and T. Y. Chang. 2015. Acyl-coenzyme A:cholesterol acyltransferase 1 blockage enhances autophagy in the neurons of triple transgenic Alzheimer's disease mouse and reduces human P301L-tau content at the presymptomatic stage. Neurobiology of aging 36: 2248-2259.
Shibuya, Y., C. C. Chang, L. H. Huang, E. Y. Bryleva, and T. Y. Chang. 2014. Inhibiting ACAT1/SOAT1 in microglia stimulates autophagy-mediated lysosomal proteolysis and increases Abeta1-42 clearance. J Neurosci 34: 14484-14501.
Production of ACAT1 56-kDa isoform in human cells via trans-splicing involving the ampicillin resistance gene. Hu, G. J., J. Chen, X. N. Zhao, J. J. Xu, D. Q. Guo, M. Lu, M. Zhu, Y. Xiong, Q. Li, C. C. Y. Chang, B. L. Song, T. Y. Chang, and B. L. Li. 2013. Cell research 23: 1007-1024.
Huang, L. H., K. Nishi, S. Li, T. Ho, R. Dong, C. C. Y. Chang, and T. Y. Chang. 2014. Acyl-coenzyme A:cholesterol acyltransferase 1 - significance of single-nucleotide polymorphism at residue 526 and the role of Pro347 near the fifth transmembrane domain. The FEBS journal 281: 1773-1783.
Huang, L. H., J. Gui, E. Artinger, R. Craig, B. L. Berwin, P. A. Ernst, C. C. Y. Chang, and T. Y. Chang. 2013. Acat1 gene ablation in mice increases hematopoietic progenitor cell proliferation in bone marrow and causes leukocytosis. Arteriosclerosis, thrombosis, and vascular biology 33: 2081-2087.
Murphy, S. R., C. C. Y. Chang, G. Dogbevia, E. Y. Bryleva, Z. Bowen, M. T. Hasan, and T. Y. Chang. 2013. Acat1 knockdown gene therapy decreases amyloid-beta in a mouse model of Alzheimer's disease. Molecular therapy 21: 1497-1506.
Rogers, M. A., J. Liu, M. M. Kushnir, E. Bryleva, A. L. Rockwood, A. W. Meikle, D. Shapiro, B. L. Vaisman, A. T. Remaley, C. C. Y. Chang, and T. Y. Chang. 2012. Cellular Pregnenolone Esterification by Acyl-CoA:Cholesterol Acyltransferase. The Journal of biological chemistry 287: 17483-17492.
Bryleva, E. Y., M. A. Rogers, C. C. Chang, F. Buen, B. T. Harris, E. Rousselet, N. G. Seidah, S. Oddo, F. M. LaFerla, T. A. Spencer, W. F. Hickey, and T. Y. Chang. 2010. ACAT1 gene ablation increases 24(S)-hydroxycholesterol content in the brain and ameliorates amyloid pathology in mice with AD. Proceedings of the National Academy of Sciences of the United States of America 107: 3081-3086.
Chang, C. C. Y., A. Miyazaki, R. Dong, A. Kheirollah, C. Yu, Y. Geng, H. N. Higgs, and T. Y. Chang. 2010. Purification of Recombinant Acyl-Coenzyme A:Cholesterol Acyltransferase 1 (ACAT1) from H293 Cells and Binding Studies between the Enzyme and Substrates Using Difference Intrinsic Fluorescence Spectroscopy. Biochemistry 49: 9957-9963.