Dr. Ko’s research is focused on determining the molecular pathogenesis of infectious diseases with emphasis on innate immune modulation of bacteria proteins. The manifestation and progression of infectious diseases are the outcomes of complex interactions between bacteria factors and host proteins. Currently, there are two lines of research.
1. Penetrating the Staph Fibrinogen Shield. Staphylococcus aureus is an opportunistic pathogen that is capable of causing life-threatening disease and the emergence of antibiotic resistant strains (i.e. MRSA) highlights the need for novel and effective therapeutics. All S. aureus vaccines tested so far have been ineffective and we think we now know why. We have discovered that S. aureus assembles a shield around itself containing the host protein, fibrinogen. This shield protects the microbe from being killed and removed by the host defense systems. We believe this shield is a likely cause for the failure of all clinical trials that have focused on using antibody vaccination strategies. The goals of the project are to understand the mechanisms used by the bacteria in forming the protective fibrinogen shield and we are exploring strategies to prevent its formation.
2. Bacterial evasion of the complement system. The complement system is not only the first line of defense against microorganisms, but also an important arm of our innate immune response. Complement factors circulate in our plasma in an inactive form, but are rapidly activated upon contact with invading microorganisms or altered self-surfaces. The activation of the complement system has three important outcomes: A) labeling of bacteria with C3b for efficient uptake by phagocytes; B) generation of chemoattractant molecules (C3a/C5a) to recruit immune cells to the sites of infection; C) formation of membrane attach complex for direct killing of Gram-negative Bacteria. Research in lab demonstrated that bacteria proteins, including surface proteins and secreted proteins, not only binds host plasma protein fibrinogen but also recruits complement factors. The goals are to understand the molecular mechanism of the interactions and the precise biological functions of the interactions. One area of deep interest is to elucidate how bacteria manipulate fibrinogen-centered coagulation system and complement system simultaneously to tip these two important host defense mechanisms in favor of bacteria.