Research Interest:

Protein Folding/Misfolding, Amyloids, and Neurodegenerative Diseases

My research focuses on understanding the mechanism of protein misfolding diseases, amyloidosis, by various techniques including biochemical, biophysical, molecular, and cellular methods. Our long-term goal is to elucidate the disease mechanisms of amyloidosis in the aspects of protein folding and structure, pathogenic protein interactions, and relate the results to the medical consequences. We further utilize the knowledge to develop novel diagnostic means and therapeutic modalities. Many ageing-related neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) belong to amyloidosis. Among them, AD is the most serious problem in the 21st century. Amyloidosis is caused by aggregation of misfolded proteins to form amyloid fibrils comprising specific cross-β structures. Amyloid oligomers that exist in several neurodegenerative diseases imply a common toxicity mechanism in different neurodegenerative diseases. Currently, we are working on three amyloid and amyloid-like proteins and their interacting partners in neurodegenerative diseases. They are amyloid-β (Aβ) peptide and tau protein, the major substance in senile plaques and neurofibrillary tangles of AD patients respectively, α-synuclein, the component of Lewy bodies in PD, and TDP-43, a novel inclusion found in a subtype of frontotemporal lobar dementia (FTLD-U), amyotrophic lateral sclerosis (ALS), and AD. We start from elucidating the mechanism of such aggregation and further developing the diagnostic method, antibodies, and small molecule inhibitors. Moreover, we study the structure, function, and interactions of the related glycan conjugates, precursor proteins, and modifiers. The major research interests are listed as follows:

• Protein folding and misfolding of amyloids in neurodegenerative diseases.

• Amyloid protein oligomerization and the toxicity mechanisms in neurodegenerative diseases.

• Interactions of proteins, glycans, and lipids with the proteins involved in pathogenesis of the neurodegenerative diseases.

• Drug screening, diagnostic, and therapeutic developments in neurodegenerative diseases.

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