MSTP in PhD Training
Current advisor: Juliane Bubeck Wardenburg, MD, PhD
Undergraduate university: University of California-Berkeley, 2015
Enrollment year: 2018
Mechanisms of T cell immunity to S. aureus
Staphylococcus aureus is a Gram positive commensal bacterium that causes major disease and disability in adults and children, including bacteremia, sepsis, and skin and soft tissue infection (SSTI). S. aureus- associated disease is particularly concerning due to the growing threat of antimicrobial resistant strains (ex. methicillin-resistant S. aureus, MRSA) and the lack of an effective vaccine against the pathogen. We hypothesize that the development of effective therapeutics against S. aureus is encumbered by an insufficient understanding of the native development of immunity against S. aureus, especially as this relates to T cells. Previous data from our lab and others suggest that the adaptive immune response to S. aureus develops early in life. This coincides with early-in-life skin colonization by S. aureus – up to 60% of infants are colonized on the skin with S. aureus within the first few days of life. Exposure to bacteria during infancy and early childhood can lead to immune imprinting, whereby the host immune response is shaped by antigens produced by the colonizing bacteria. However, S. aureus produces a variety of toxins that significantly interfere with the development of a protective immune response in humans. One S. aureus toxin studied in our lab, the ubiquitously expressed cytolytic toxin a-toxin (Hla), is an essential virulence factor in disease pathogenesis and has also been shown to impair the T cell-mediated response to experimental S. aureus skin infection. Our studies of how Hla impedes development of host immunity underscore the critical role of T cell immunity against S. aureus and reinforces the importance of a comprehensive understanding of how anti-S. aureus T cell immunity develops during the normal course of exposure to a pathogen. The objective of this project is to define the development and function of the antigen-specific T cell response to S. aureus in young children and in mouse models of disease, respectively. To this end, we will pursue an in-depth examination of the human T cell response in early life and undertake mechanistic studies in mice to more specifically define how Hla modulates the T cell response. Together, these studies will provide a critical context within which future therapeutic development must operate to develop effective, long-term protection against S. aureus-associated disease.