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Cell Metabolism in Nervous System

Brain cells consume copious amount of energy substrates for various functions. To coordinate substrate input and energy demand, cell organelles are required for orchestrating the evolutionarily conserved metabolic pathways. The intricate interactions between different organelles are pivotal in regulating metabolite trafficking, cell growth, metabolism, immune response, intercellular signaling, etc. Misrouted inter-organellar signaling leads to disrupted bioenergetic processes, and impairs the functions of energy demanding system such as the central nervous system. Indeed, perturbations to dysfunctional mitochondria and/or endolysosomes, two organelles fundamental to cell metabolism, often result in neurological disorders.

Research Approach

Deciphering the molecular underpinning of cell metabolism and bioenergetics will have huge impact on how we approach human diseases pertinent to immune and nervous systems. In our lab, we undertake a multi-disciplinary approach that integrates bioinformatics, model organism genetics, cell biology, lipidomics, and quantitative microscopy to study the cell biology of endolysosomes in brain and immune cells. We use the genetically tractable organism, Drosophila, to model organellar functions and map out the intricacy of the cellular pathways. Due to the versatility, robustness, and convenience of the genetic tools available to Drosophila research, we can swiftly build mechanistic models for specific cellular processes, and test novel concepts on relevant mammalian cells and animal models.

Organellar Signaling and Bioenergetics in Disease

One of the main focuses of our research is to study how endolysosomes participate in organellar signaling and bioenergetics. Endolysosomal functions are particularly paramount to the immune and nervous systems, where pronounced phenotypes are manifested in lysosomal storage and neurodegenerative disorders. Our goal is to decipher the mechanisms of how endolysosomes coordinate signaling modules in different cell types in the nervous system, and to understand the pathogenesis of related diseases at molecular level. To this end, we utilize a multi-disciplinary approach which encompasses bioinformatics, model organism (Drosophila & mouse) genetics, high-resolution imaging, and disease-associated cell models. Our long-term goal is to leverage the mechanistic findings to develop therapeutic concepts for treating degenerative diseases that involve endolysosomal dysfunction.

Our research programs involve studies of vesicular trafficking, glial cell bioenergetics, transcellular signaling, and neuro-immune interaction. We are currently pursuing the following:

1) Dissecting the roles of metabolic organelles in neuroglial lipid transport and lipid metabolism in neurodegenerative disorders such as Alzheimer’s.

2) Deciphering how vesicular transport and organellar signaling regulate metabolic and bioenergetic processes in glial cells.

3) Studying how endolysosomes modulate signaling pathways in macrophage in response to microbes and damaged tissues.

4) Mechanism and functional outcome of the interplay between immune and nervous systems in the context of neurodegeneration.

 

Our research is funded by:

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