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| Name |
Chang, Ta Yuan |
| Location
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Geisel School of Medicine at Dartmouth |
| Primary Field
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Medical Physiology and Metabolism |
| Secondary Field
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Biochemistry |
 Election Citation
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Ta Yuan Chang studies cholesterol homeostasis in the central nervous system and systemic tissues, with a focus on the enzyme that detoxifies and stores cholesterol. |
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Research Interests
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The Chang lab, with T.Y. as the PI and Catherine as the co-I, studies cholesterol homeostasis in the central nervous system and in systemic tissues, with a focus on investigating the biochemistry and physiological roles of the cholesterol storage enzyme acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), named as sterol O-acyltransferase 1 (SOAT1) in GenBank.
ACAT1 is a membrane bound protein in the endoplasmic reticulum. It plays a key role in the cholesterol storage process. Our laboratory discovered the Acat1/Soat1 gene. In many neurodegenerative diseases, cholesterol dys-homeostasis occur; in addition, the cholesterol-rich membrane microdomains in various neuronal cell types are damaged. We showed that, in mouse models for Alzheimer's disease (AD) and for Niemann Pick type C disease (NPCD), blocking cholesterol storage by inactivating the Acat1 gene can divert the cholesterol storage pool, such that the "mobilized" cholesterol facilitates cholesterol homeostasis and repairs the damaged membrane microdomains. Current and future investigations are directed to develop brain-permeable ACAT inhibitors, to investigate the consequences of inhibiting ACAT in cells, and to elucidate the biochemical mechanism that governs sterol-specific activation of ACAT in vitro. |
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