My research focuses on how bacterial pathogens cause human diseases. I am particularly interested in understanding the roles of bacterial toxins and other virulent factors in bacterial pathogenesis and developing novel therapeutics against infection. Bacterial toxins and virulence factors that are also excellent model systems for us to investigate fundamental processes of biological sciences, including protein-membrane interaction, protein pore formation and membrane translocation.
Current research projects
1. Mycobacterium tuberculosis ESX-1 secreted proteins: While a lot of effort has been made to prevent and treat tuberculosis in the past century, Mycobacterium tuberculosis remains one of the world’s leading infectious agents, killing 2–3 million people each year and infecting one-third of the world’s population. The extreme success of M. tuberculosis as a pathogen is attributed to its remarkable ability to modulate and evade a variety of host defense mechanisms. Understanding the details how M. tuberculosis manipulates host defense will help develop therapeutics and vaccines for treatment and prevention of tuberculosis. Recent research has shown that one genetic locus of M. tuberculosis, termed ESX-1, is required for the virulence of M. tuberculosis, and ESX-1 appears to encode a novel protein secretion system that secretes a number of proteins of unknown function. My lab is trying to understand the structure and function of the ESX-1 secreted proteins, such as ESAT-6 (EsxA) and CFP-10 (EsxB), particularly how they interact with host membranes and evade the host defense.
2. Structure and function of the anthrax toxin receptors: Anthrax toxin is a tri-partite A-B toxin composed of two A-moieties (enzymatic), called lethal factor (LF) and edema factor (EF), and one B-moiety (binding), called protective antigen (PA). Intoxication requires anthrax toxin bind to cell surface receptors and be internalized into the endosomes through receptor-mediated endocytosis. In endosome the acidic pH triggers PA undergo conformational change to insert into the endosomal membranes and form a protein-conducting channel that translocates LF/EF across the membranes into the cytosol. While two anthrax toxin receptors have recently been identified, neither is known about their roles in regulation of toxin pore formation nor their native cellular function. We are currently working on purification and structural determination of the receptors to further extend our knowledge of the receptor function.