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How are cellular structures and functions coupled, how do they exhibit heterogeneity across the scale in live organisms, and how do they undergo changes with time as an organism grow old? We want to study these questions using multidisciplinary approaches.
My current research program is to decode the chemical language that orchestrates cellular homeostasis and organismal healthspan. One of the central questions in biology is how cells maintain their homeostatic state by adjusting to continuous internal and external changes. Metabolic activity is at the nexus of cellular homeostasis, generating thousands of intermediates and products as metabolites. These metabolites are directly connected with cellular activities and well conserved across different species from prokaryotes toeukaryotes. Despite their well-known functions as structural building blocks and energy sources, how metabolites act as chemical communication cues between organelles within and between cells, with the outside environment, and even across species remains largely unknown. To understand and manipulate metabolite-directed communication systems that promote the healthy survival of an organism, my laboratory has been taking multidisciplinary approaches and focus on three metabolite-based communication systems in different spatial scales, encompassing 1) lysosomal metabolite-directed inter-organelle and inter-tissue crosstalk, 2) bacterial metabolite-mediated microbe-mitochondria dialogue, and 3) volatile metabolite-initiated long-range signaling. We are also interested in new technological paradigms to deepen these mechanistic characterizations, such as organelle-specific metabolomics and proteomics, photo-highlighting based high-throughput/high-resolution genomic screening, and stimulated Raman scattering microscopy for in vivo metabolite tracking.
New Research Areas at Janelia
The overarching goal for our future studies is to understand how organelle structure and function are coupled within the cell, how they exhibit heterogeneity in different organs, and how they undergo changes with time in live organisms. Eukaryotic cells are made up of different compartments (lysosomes, mitochondria, lipid droplets, etc.) with specialized functions. These compartments are tightly connected with each other and their harmonic cooperation is essential for achieving optimal fitness for the cell and ultimately for the organism. Through harnessing the power of functional genomics, multiplex microscopy imaging and organelle/cell-specific multi-omics profiling, we will want to 1) Link organelle connectivity and functionality in time and space, 2) Provide molecular basis governing organelle heterogeneity, 3) Understand physiological individuality in metabolism and longevity.