From mitochondrial mechanisms to disease-modifying therapies
We study how mitochondrial dynamics, proteostasis, metabolism and organelle communication shape neuronal health and disease. By integrating molecular and cellular biology, proteomics, genomics, patient-derived iPSC models and disease-relevant animal models, we identify mechanisms that drive neurodegeneration and convert them into therapeutic opportunities.
Mitochondrial Dynamics & Quality Control in 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, immune response and neuron-glia communication in various neurodegenerative diseases.
Zhao et al., Nat Commun 2022
Zhao et al., Nat Commun 2019
Mitochondrial Proteostasis & Organelle Homeostasis Under Normal and Diseased Conditions
Mitochondrial proteostasis is essential for maintaining mitochondrial protein integrity and overall organelle quality. Using unbiased proteomic approaches, we aim to identify key factors that regulate mitochondrial protein homeostasis. Our research focuses on understanding how mitochondrial proteostasis supports cristae structural stability, coordinates communication between cellular and subcellular organelles, and contributes to the mechanisms underlying neurodegeneration.
Hu et al., Acta Neuropathol 2019;
Shang et al., Acta Neuropathol 2022;
Hu et al., Mol Neurodegener 2025
Mitochondrial Metabolism & Neuroimmune Regulation In Neurodegenerative Disease
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.
Zhang et al., Science Advances, 2020
Therapeutic Discovery- Development of Mitochondrial Medicine
A major translational arm of our research focuses on converting mechanistic discoveries into therapeutic strategies. We develop rationally designed peptide inhibitors that target disease-driving protein–protein interactions and use high-throughput screening to identify small molecules that restore mitochondrial function.
