Our research interests are centered around microbial pathogens and the impact of human microbial flora on human health and disease. The current focus is on 1) virulence determinants of Staphylococcus aureus and 2) relationship of the oral microbial community and oral cancer.
Staphylococcus aureus is one of the most successful human pathogens, asymptomatically colonizing over 2 billion individuals worldwide and capable of causing invasive and deadly opportunistic infections. We are using genomic approaches to identify virulence determinants associated with S. aureus infections and determine their roles in pathogenicity. The numerous putative virulence factors we have identified include toxins, bacterial surface proteins that mediate adhesion to host tissue as well as putative regulatory elements and genes with possible roles in evasion of innate immunity. We are currently using in vivo and in vitro experimental approaches to verify the functions of these genes. In addition, we have recently initiated a systems biology approach employing animal infection models, deep genome sequencing and RNAseq transcriptome analysis to identify the genomic and transcriptional basis of chronic and complicated S. aureus infections.
In addition to Staphylococcus aureus, the Staphylococcal family includes several species which are emerging as pathogens of clinical relevance. We are currently working on Staphylococcus epidermidis and the contribution of vertical and horizontal genome evolution to their increased virulence. In S. epidermidis, we have identified a putative pathogenicity island (SePI), which appears to have been acquired by cross-species mobilization from S. aureus. We are attempting to determine the mobilization mechanism of the SePI and its role in virulence.
Association of the oral microbial community with oral cancer
Oral cancer is one of the top ten most common cancers, with the incidence increasing in the United States and many other parts of the world. The prognosis for oral cancer is markedly poor, with the average all-stage, 5-year survival rate under 50%. Worldwide, oral cancer is the sixth most prevalent cancer with over 300,000 new cases diagnosed each year. In the United States alone, 30,000 new cases are diagnosed each year with an anticipated 8,000 deaths attributed to the disease.
A major component of the human oral cavity with a direct role in oral health and disease is the oral microbiota or oral microbiome, a complex community of over 800 bacterial species that exist in a dynamic and intimate relationship with the oral surfaces of the human host. Progression from oral health to disease is associated with a shift in oral microbiome community structure and the emergence of potential oral pathogens. Our overall hypothesis is that there is an oral cancer microbiome with a distinct community structure and functional features that can initiate tumorigenesis through interaction with the oral tumor microenvironment.
Using 454-pyrosequencing phylogenetic analyses to identify microbial community structure, we have demonstrated that the oral tumor microenvironment harbors a distinct population of phyla, genera and species not found in healthy oral tissue. We are currently using 454 metagenomic analyses to identify the functional capacity of these same microbial communities as well as identify other members of the tumor microbial community, including viruses, fungi and Achaea. Finally, we have demonstrated that bacterial species cultivated from the oral tumor microenvironment impact cell signaling pathways responsible for initiation and progression of oral cancer.