Wu, Chun

• Ph.D., University of New Mexico, Alberquerque 

• M.S., Sichuan University 

• B.S., Sichuan University

My research focuses on two topics:

i) Development of a new class of antibiotics targeting bacterial energy metabolism. The current rise in antibiotic-resistant bacteria, such as Methicillin-Drug Resistant Staphylococcus aureus (MRSA), NDM-1-induced antibiotic-resistant E. coli, has created an urgent need for alternative antibiotics. The long-term goal of this project is to develop novel antibiotics that are less susceptible to bacterial resistance. MRSA was chosen as the model organism due to its significance as a major resistant pathogen. Our hypothesis suggests that specific central metabolic enzymes, such as MRSA acetate kinase (ACK) and MRSA fructose bisphosphate aldolase (FBPA) are essential for bacterial growth and absent in humans, making them ideal drug targets. This project focuses on three aims:

• Target Validation: Confirm enzyme essentially in pathogenic bacteria via allelic replacement and inducible gene expression

• Enzyme Characterization and Inhibitor Design: Characterize enzymes using kinetic assays and crystal structure analysis, followed by ligand-based drug optimization

• In Vivo Inhibitor Development: Assess lead inhibitors for antibacterial efficacy and enhance bacterial membrane permeability

ii) Pathogenesis of Multiple sclerosis. Multiple sclerosis (MS) is an autoimmune disorder characterized by  the immune system's attack on the myelin sheath of neurons. Although the cause of MS remains unclear, there are some hypotheses, among which the viral hypothesis, particularly involving the Epstein-Barr virus (EBV), is prominent. The long-term objectives of the project is to develop vaccines that target or modulate the immune response to antigens targeted by autoantibodies in MS patients, reducing the risk of cross-reactivity and subsequent autoimmune attacks on myelin; develop novel therapeutic tools aimed at desensitizing the immune system to these specific antigens, preventing or reducing autoimmune attacks; improve diagnostic tools, allowing for earlier and accurate detection of MS and potentially identifying individuals at risk. The specific aims are: 

• Identify antigens targeted by autoantibodies in MS patients.

• Investigate if humans MS mimics myelin-mimicking proteins from pathogens like EBV or others.

• Determine if disease type and severity depend on the pathogen and whether disease progression follows a pathogen-specific sequence.

• Explore if a consortium of microorganisms triggers demyelination and whether the disease type and progression are pathogen-dependent.

• Assess the role of low vitamin D3 and genetic factors in modulating autoantibody formation and disease course in relation to the initiating pathogen.