Investigator: Dr. Wenxue Li

Research Associate, Department of Neurology

Dr. Wenxue Li received his Ph.D. from the Shanghai Institute of Biochemistry Chinese Academy of Sciences. He then went on to complete postdoctoral training in Neuropathology at the Johns Hopkins University. In 2005, Dr. Li joined the Nath laboratory and is currently a Research Associate in the Department of Neurology of the Johns Hopkins University School of Medicine.

Dr. Li’s research focuses on the pathogenesis of neurodegenerative diseases. He has extensive experience in studying the mechanisms of neuronal death induced by toxic proteins and other neurotoxins. He is currently engaged in uncovering the neuropathogenesis of HIV associated dementia (HIVD). One of the critical players in the pathogenesis of HIVD is oxidative/nitrosative stress. Dr. Li found that patients with active HIVD have increased 3-nitrotyrosine modification of proteins in CSF, and intravenous drug use can further increase the accumulation of such proteins. Interestingly, oxidative/nitrosative stress may also serve as one of the host defense systems, as nitration of viral protein Tat may attenuate its neurotoxicity. In addition, NMDA receptor is involved in many neurodegenerative diseases and also in HIVD. Viral proteins may interact with NMDA receptor and the overactivation of NMDA receptor may cause neuronal death. Thus, understanding the role of oxidative/nitrasative stress and NMDA receptor in HIVD may provide us new insight into the pathogenesis of HIVD and may help the design of new antioxidants and neuroprotective therapy.

Dr. Li’s current projects include:

1. How do viral proteins and drugs of abuse lead to the nitration of brain type prostaglandin D synthase (L-PGDS)? As L-PGDS is the major protein nitrated in the patients of active HIVD and drug abuse, understanding the mechanism of nitration of L-PGDS and the effects of viral proteins and drugs of abuse on prostaglandin pathway will be critical for the neuropathogenesis of HIVD.
2. What is the mechanism of HIV-1 inhibition by nitric oxide? Nitric oxide can cause oxidative/nitrasative stress in neurons, but it also inhibits HIV replication. Our data suggest that nitric oxide may inhibit HIV by S-nitrosylation of viral protein Tat. It’s possible that other viral proteins and cellular factors are the target of modification by nitric oxide. Identifying these factors may be important for the design of new anti-HIV drugs.
3. Understanding the interaction between viral protein and NMDA receptor. NMDA receptor is involved in HIV-induced neurotoxicity. But the mechanism is not clear. Our data indicate that Tat can directly bind to and cause neuronal death through NMDA receptor. How Tat interacts with NMDA receptor and causes toxicity needs to be revealed.