Research in my laboratory is focused upon the role of the microbome in human dysbiotic diseases. We study the human oral microbiome as our model system to understand the role of microbial ecology in determining health and disease at mucosal sites in the human body. The cariogenic species Streptococcus mutans is our primary organism of interest for genetic studies of microbiome pathobiology. However, our research also often includes a variety of other oral microbiome species, especially for studies of interspecies interactions among the oral microbiota. We are also interested in the mechanisms of synergistic pathogenesis that occur between different microbiome species during dysbiosis. Few efficacious treatment options are available for the many types of chronic dysbiotic diseases, such as oral diseases, irritable bowel disease, urinary tract infections, etc. The treatment of such diseases poses a unique challenge because the few species associated with pathology naturally live amongst potentially hundreds of other beneficial species in mixed communities. Thus, the typical antibiotic treatment approaches used for many other types of infections are either ineffective or can result in serious side effects. Ultimately, effective solutions will require new ecological treatment strategies to reestablish a symbiotic microbiome.
For our S. mutans studies, we are currently focusing on two main research projects. The first project is focused upon post-transcriptional gene regulation. An abundance of recent evidence in a variety of pathogens indicates that most of the critical regulation of virulence occurs post-transcriptionally, yet remarkably little is known about post-transcriptional control mechanisms, especially for organisms involved in dysbiotic diseases. Of central interest is to determine how a diverse array of environmental stress signals can activate these pathways to modulate downstream gene expression. The second project involves a new class of prokaryotic signal transduction system that we discovered in S. mutans and now refer to as LytTR Regulatory Systems (LRS). LRS appear to be widely conserved in prokaryotes, but nearly all are currently uncharacterized. In S. mutans, LRS activation can trigger lethality. Therefore, we are interested to determine how LRS transduce sensory information as well as the mechanisms responsible for lethality.
For our polymicrobial infection studies, we have developed a murine abscess model that is critically dependent upon polymicrobial synergism for virulence. Key oral microbiome species in our model include Streptococcus anginosus, Fusobacterium nucleatum, Prevotella nigrescens, and Parvimonas/Peptostreptococcus species. In addition to oral abscesses, these species are routinely isolated from numerous extraoral infections, such as severe liver, lung, and brain abscesses, yet it is entirely unclear how and why these infections occur. Our major interest is to use this model system to understand how a pathogenic community can dysregulate the immune response and trigger immunopathology, which is a hallmark of all chronic inflammatory dysbiotic diseases.
For additional information: http://www.ncbi.nlm.nih.gov/myncbi/browse/collection/41151868/?sort=date&direction=descendingRead more
Areas of interest
- Symbiosis and Dysbiosis
- Bacterial Genetics
- B.S., University of Miami, Coral Gables Florida 1997
- Ph.D., University of California Los Angeles, Los Angeles California 2004
- NIH Pre-IRTA Fellowship 1997-1999
Honors and awards
- 2019 OHSU Faculty Senate Award for Research
Memberships and associations
- American Association of Dental Research Science Information Committee
- International Association for Dental Research (IADR) & American Association for Dental Research (AADR)
- American Society for Microbiology (ASM)