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Our research aims to understand how human-restricted bacterial pathogens colonize host tissues and evade the host’s otherwise effective immune response. Our paradigm is the pathogenic Neisseria sp., which includes the bacteria that cause the sexually transmitted disease gonorrhea and rapidly progressing invasive meningococcal meningitis. These bacteria are highly adapted to life in humans, undergoing constant evolution of surface antigens via a combination of antigenic and phase variation, and actively suppressing both innate and adaptive immune responses. Our studies in this regard have led to the development of more relevant in vitro and in vivo models of neisserial infection and disease; to a detailed description of molecular processes that occur downstream of immune activating and inhibitory carcinoembryonic antigen-related cellular adhesion molecule (CEACAM)-related proteins; to reveal a previously unrecognized ‘pathogen-associated molecular pattern’ (PAMP) that allows innate immune detection of bacterial in the tissues; to provide new molecular and immunological insights into the epidemiological synergy between sexually transmitted gonorrhea and HIV-1; to the development of novel vaccines with the potential to broadly protect against neisserial infection; and to the development of a new class of antibiotics that function by activating cylindrical proteases within the bacterial cytoplasm.
Our research aims to understand how human-restricted bacterial pathogens colonize host tissues and evade the host’s otherwise effective immune response. Our paradigm is the pathogenic Neisseria sp., which includes the bacteria that cause the sexually transmitted disease gonorrhea and rapidly progressing invasive meningococcal meningitis. These bacteria are highly adapted to life in humans, undergoing constant evolution of surface antigens via a combination of antigenic and phase variation, and actively suppressing both innate and adaptive immune responses. Our studies in this regard have led to the development of more relevant in vitro and in vivo models of neisserial infection and disease; to a detailed description of molecular processes that occur downstream of immune activating and inhibitory carcinoembryonic antigen-related cellular adhesion molecule (CEACAM)-related proteins; to reveal a previously unrecognized ‘pathogen-associated molecular pattern’ (PAMP) that allows innate immune detection of bacterial in the tissues; to provide new molecular and immunological insights into the epidemiological synergy between sexually transmitted gonorrhea and HIV-1; to the development of novel vaccines with the potential to broadly protect against neisserial infection; and to the development of a new class of antibiotics that function by activating cylindrical proteases within the bacterial cytoplasm.
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