Mitochondrial dynamics and neurodegenerative diseases

Mitochondria are highly dynamic organelles that constantly divide and fuse in cells. Mitochondrial fission and fusion (mitochondrial dynamics) influence not only mitochondrial morphology, but also mitochondrial biogenesis, mitochondrial distribution within the cell, and cell death.  Our research goal is to understand the roles of mitochondrial dynamics (fusion and fission)-related proteins in the regulation of mitochondrial function, genome stability, lipid metabolism, and neuron-glia communication, in Huntington’s, Parkinson’s and Alzheimer’s diseases.

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Mitochondrial protein and organelle homeostasis under normal and diseased conditions

Mitochondrial proteostasis and mitochondria-associated autophagy (mitophagy) are events that are important to maintaining mitochondrial proteins and organelle quality. Using an unbiased proteomics approach, we are identifying factors that participate in these events, and aim to understand how protein homeostasis of mitochondria controls neuronal life, mediates cellular communications, and influences neurodegeneration.

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Oligodendroglial metabolism, neuroinflammation, and neurodegenerative diseases

Myelin degeneration and white matter loss that result from oligodendrocyte (OL) death are early events in neurodegenerative diseases that lead to cognitive deficits and correlate with disease status. OLs are the most abundant glial cell type in the brain but the least studied cell population in the context of neurodegeneration, despite their vital role in myelin maintenance and neuronal support. The underlying mechanisms of OL dysfunction and its contribution to the initiation and progression of neurodegeneration remain largely unknown. Using a variety of experimental approaches, we are investigating the detailed molecular pathways and metabolic signatures in OL lineages that contribute to neuroinflammation and the progression of neurodegenerative diseases.

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Zhang et al., Science Advances, 2020

Development of mitochondrial enhancers for treatment of human diseases

As another arc of our research, we have been developing therapeutic options for the treatment of neurological disorders by targeting damaged mitochondria. We utilize rationally designed peptide inhibitors of protein-protein interactions and high throughput screening to developing “mitochondrial medicine” as therapeutic strategies for treating neurodegenerative diseases and other diseases in which mitochondrial dysfunction manifests.

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Hu et al., Nature Communications, 2021