Phone: 352-273-8850 Room: D5-18 P.O. Box 100424
- Host-pathogen interactions
- Structure-function of streptococcal surface proteins
- Immunogenicity/vaccine development
Our research program is concerned with mucosal immunity and its role in host defense, and in the mechanisms by which pathogens subvert host defenses. One of our major areas of interest is molecular vaccines. We are investigating the use of live attenuated Salmonella strains as vehicles to deliver cloned antigens to the Peyer’s patches in the gut in order to efficiently stimulate a mucosal IgA response. Because an immune response can be elicited to a selected antigen and not to the entire organism, problems associated with undesirable and potentially dangerous side effects of whole cell vaccines can be avoided.
The primary interests in my laboratory are in the molecular mechanisms governing the ability of bacteria that are capable of causing diseases in humans to modulate their virulence in response to environmental influences. The specific projects in the lab are focused in three major areas. The first is a detailed study of the genetics and physiology of polysaccharide metabolism and its relationship to virulence and biofilm formation by oral streptococci. The second project is a molecular genetic analysis of the role of the major molecular chaperones in gene regulation and responses to environmental stresses. The third project is a broad based approach to understanding the genetics and physiology of ureases and arginine metabolism by streptococci and actinomycetes.
Our laboratory is primarily interested in autoimmunity with the focus in autoantigens and autoantibodies associated with systemic autoimmune diseases, such as Sjögren’s’ syndrome, and oral cancer. The two main directions are 1) to identify and characterize specific autoimmune target antigens and understand why autoantibodies are induced and continually produced in different disease states and 2) to use human autoantibodies as unique probes to reveal the molecular and cellular functions of interesting macromolecules and subcellular organelles that are autoimmune targets. By understanding the biology of autoantigens in health and disease states, we can appreciate the functional and pathogenic potentials of autoantibodies.
We have identified several novel autoantigens in cytoplasmic foci known as GW bodies (GWB, or RNA processing bodies, PB). Recent data from our laboratory demonstrate cellular functions for these cytoplasmic structures to include siRNA and miRNA mediated function. Specifically our current data suggest that the size and number of GW/P bodies are cellular biomarkers for the RNA interference (RNAi) pathway including both siRNA and miRNA functions. Our laboratory will continue to examine the role of GW/P bodies in cellular miRNA function, their contribution to different disease processes, and the use of RNAi for therapeutics especially in oral medicine and oral cancer.
We apply multidisciplinary approaches (morphological, physiological, pharmacological, biochemical, molecular and genetic) to study the biology of salivary glands, with an emphasis on the synthesis, secretion and functions of mucins. Mucins are major constituents of mucus layers of the body and function as a defense mechanism against invading microorganisms. These glycoproteins are secreted by the highly specialized mucous cell phenotype, which are under complex parasympathetic control. We recently discovered and characterized the gene, Muc19/Smgc, which encodes the mucin (Muc19) that is selectively expressed by mouse sublingual salivary glands. Coincidently, we genetically mapped an autosomal recessive mutation, sld, to a 1 megabase critical region of chromosome 15. The sld phenotype is characterized by the developmental delay and attenuated expression of Muc19. Interestingly, the critical region contains Muc19/Smgc. We are currently delineating whether Muc19 indeed harbors the sld mutation, through construction of knockout mouse models and by bioinformatic/gene expression analysis of the critical region. We are also investigating the associated genetic lesion to determine mechanism(s) by which steady-state levels of Muc19 transcripts are regulated. We recently initiated a project to induce distinct targeted gene deletions of specific salivary constituents (e.g., Muc19) in mice to test their functions in protecting teeth against the oral pathogen, Streptococcus mutans. Genetic manipulations of the bacteria are also being carried out to test putative S. mutans virulence factors in caries development. Determination of the influence of specific bacterial and host determinants in caries development in vivo may ultimately provide important targets for therapeutic intervention in the treatment of patients at high risk for caries.
- Periodontal disease: etiology, diagnosis, progression, prevention and therapy
- Clinical Research
- Clinical Trials
- Molecular biology of virulence of periodontal pathogens
- The molecular basis of the associations of periodontal disease and cardiovascular diseases
- Novel technologies of studying in vivo gene expression in pathogenic organisms
Porphyromonas gingivalis is an important periodontal pathogen. Recently, it has been recognized that P. gingivalis may have an important role in systemic diseases, including cardiovascular disease, prematurity, and low birth weight.
Project 1. Cardiovascular diseases are the leading cause of death in developed countries. We use human coronary artery endothelial cells as model to study the interactions of P. gingivalis with the endothelial layer of the vasculature.
Project 2. Prematurity and associated low birth weight are the leading cause of death in the first month of life. We developed a rat model to study adverse pregnancy outcomes during infection with P. gingivalis. We aim to elucidate the mechanisms by which P. gingivalis virulence factors and the host immune system interact to cause pregnancy complications.
- Mechanisms of antibiotic resistance and the transfer of resistant determinants in oral biofilms using an in vitro biofilm model
- Effects of antibiotics on biofilms relative to planktonic cultures (in broth)
- Live-dead assays of biofilms
- Matrix metalloproteinases (MMPs) levels in children with and without aggressive periodontal disease
- Characterization of subgingival flora in children with periodontitis using DNA-DNA hybridization