Laboratory of
Mechanisms of Neurodegenerative Diseases
Research Interests

Neurodegenerative diseases (NDD), including Alzheimer¡¯s disease, Parkinson¡¯s disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington¡¯s disease(HD), are devastating brain disorders that gradually become health care crisis around world. Unfortunately, for all of these diseases, treatment options are limited to symptom management. No disease modifying medication is available to stop the progression of these diseases. In many cases, symptoms and neuropathological conditions overlap among these diseases, although each disease has its own distinct features. Therefore, it is important to understand the common molecular pathways leading to neurodegeneration in general and the mechanisms underlying the selective neurodegeneration unique to each disease. The goal of the lab is to gain insights into the novel therapeutic strategies by investigating the molecular mechanisms of neurodegenerative diseases. We use a number of research models (including cellular, mouse and drosophila), and a large variety of techniques.  Our current research interests are in Parkinson¡¯s disease and ALS.

Ongoing directions

Functional characterization of disease-associated proteins
Although most cases of neurodegenerative diseases are sporadic, mutations in many genes cause early onset of the diseases. Understanding the normal functions of the disease-associated proteins, and the molecular pathways affected by their pathogenic mutants,  will generate great insight into the mechanisms underlying various neurodegenerative diseases. Currently, we are investigating  the mode of actions of PD-associated proteins, including -synuclein and DJ-1, and ALS-associated proteins, such as FUS, TDP-43, Ubiquilin 2 and VCP.  We also aim to unveil the functional interactions among disease-related proteins and identify the common molecular pathways ed under disease state.

Post-translational modifications in neurodegenerative diseases
Post-translational modifications (PTMs) serve as signal switches to alter the stability, distribution, interaction patterns of the target proteins. They are readily affected by aging and environment, which are key factors contributing  to sporadic  neurodegenerative diseases . Therefore, characterization of the PTMs of key proteins involved in neurodegenerative diseases will be very important for understanding  the disease mechanisms. We are particularly interested in the regulation of  lysine modifications, such as acetylation, ubiquitination, methylation and SUMOylation, and their functional interplay. Furthermore, these modifications are frequently affected by disease-associated proteins. For example, PD-associated Parkin is a ubiquitin E3 ligase, while ALS-associated FUS is a SUMO E3 ligase. We aim to understand how PTMs affect neurodegeneration, and whether agents regulate specific PTMs could be potential therapeutics.

  

Xu, Jin, Ph.D.

Investigator
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