Projects Pathogenesis of Bacterial Infections

Staphylococcal manipulation of host immune cell assemblies

S. aureus frequently causes invasive infections due to its ability to perturb host multicellular assemblies. During infection, S. aureus secretes a plethora of potent toxins and virulence factors that together manipulate human immune cell responses thereby affecting the clinical outcome of acute and recurrent infections. To dissect the pathogen’s strategy of disrupting host multicellular assemblies, current work seeks to explore the contribution of specific human genes towards staphylococcal pathogenesis and disease. Specifically, we investigate human signaling cascades and cellular pathways targeted by S. aureus-derived cytotoxins. By using cutting-edge technologies and animal models of infectious disease, current projects also focus on the epidemiology and pathology of staphylococcal infections. Ultimately, this research may help to develop new immunomodulatory therapeutic strategies against pathogenic staphylococci, including MRSA.

Host susceptibility to staphylococcal infections

Sequence analyses of human genomes and their diversity led to the discovery of genetic polymorphisms impacting infectious diseases. However, human single nucleotide polymorphisms (SNPs) that influence staphylococcal infections are largely unknown. We investigate the hypothesis that SNPs in specific human genes are associated with the clinical outcome of S. aureus infections. In addition, we focus on chronic and recurrent infections that may have selected for specific traits in the human immune system. To achieve these goals, the laboratory takes advantage of CRISPR/Cas9 mutagenesis of host immune cells and mouse infection models. Predictions will also be validated by using unique biochemical techniques. Combined with genomic and molecular approaches, these studies are designed to answer the question why human populations exhibit variable susceptibility towards S. aureus disease.