Fatty acids are essential for life but are toxic in their free form. Subcellular organelles called lipid droplets (LDs) play an integral role in lipid metabolism by storing lipids and buffering cellular fatty acid fluctuation to prevent lipotoxicity and provide lipid sources as needed. Extensive research has shed light on how this extraordinary organelle forms and is catabolized. However, it remains elusive how LD characteristics dynamically change to support distinct cellular functions in various contexts, facilitating metabolic adaptation and tissue-specific lipid metabolism. A long-term goal of our research program is to understand how the plasticity of LD proteins and lipids shapes organelle-centric metabolic regulation at both cellular and tissue levels, focusing on the following major research directions: 

1) Determining the spatiotemporal organization of lipid metabolism in cells: What proteins and lipids constitute LDs in different metabolic conditions, and how do they shape the functional plasticity of LDs? Leveraging our expertise in genome engineering, advanced microscopy, and lipid biochemistry, we aim to profile proteins targeted to heterogenous LD populations and elucidate how they shape the fates of LDs in regulating cellular metabolism. 

2) Unraveling the functions of lipid droplets in the brain: Emerging studies have revealed abnormal LD accumulation in neurodegeneration and genetic links between neurological disorders and LD biology, suggesting their pivotal role in brain function across health and disease spectrums. Despite these insights, our current understanding of LDs in the brain remains limited, primarily due to the absence of comprehensive tools and attention from cell biologists capable of capturing their dynamic interplay with neuronal function. Utilizing various molecular toolkits and model systems we have developed, we aim to elucidate the distinct characteristics and functions of LDs in neurons, investigate their impact on motor and cognitive functions in vivo, and explore the crosstalk between neurons and glial cells in regulating lipid homeostasis.