Protein ubiquitination, amyloidosis and drug discovery of the related diseases
Our research focuses on two topics:
(1) Protein ubiquitination and linked human diseases
Post-translational modifications (PTMs) are important biological processes related to numerous cellular molecular events such as cell division, signaling ,and protein turnover. Ubiquitination is one of the post-translational modifications which employs a 76-residue small protein called ubiquitin to modify substrate proteins. Nearly half of human proteins are involved in the ubiquitination proteasome system and (mis-)regulated ubiquitinations are frequently correlated with human diseases.
We want to unravel the relationship of protein ubiquitination (or ISGylation) and infectious diseases such as SARS, Dengue fever, influenza, and Tuberculosis. These infections often substantially alter the cellular ubiquitin homeostasis hence suppress innate immunity. We employ biophysics, structural biology, biochemistry, and synthetic biology approaches to understand the infection-caused (de-)ubiquitination mechanism. By holding the knowledge, we aim to develop inhibitors against infections and enhance immunity.
(2) Protein amyloidosis and its impact on neurodegenerative diseases
The aggregated proteins called amyloid residing in the neuron cell frequently link to many neurodegenerative diseases. Parkinson’s disease is a prevalent neurodegenerative disease second to Alzheimer’s disease. There are many factors associated with Parkinson’s disease; and one hallmark is the amyloidosis of alpha-synuclein. Familial mutations, environmental factors, and foods could be the root causes of amyloidosis of alpha-synuclein. We are working on deciphering the mystery of interconversion of alpha-synuclein from intrinsically disordered protein to ordered cross-beta fibrils. By understanding the mechanism, we will have the opportunity to retard and even reverse the aggregation inside neuron cells.