Immunology, Inflammation, Microbiology, Caries & Microbiome Research

model of actin filament polymerization
 

The response of the lining of the mouth and associated skin to environmental factors, local and systemic disease, the aging process, and traumatic injury, is not well understood. Nevertheless, such responses have important implications for preventing or treating periodontal disease, oral cancer, and other soft tissue diseases. Investigating the chemical composition, structure, and permeability of this system of tissues will lead to a better understanding of the barrier function of these tissues as a defense against microorganisms and carcinogens. Studying the action of tobacco components and alcohol on the mouth lining will help better define the etiology of oral cancer and how tobacco use may contribute to periodontal disease. And understanding the interactions between the immune system and oral cancer will lead to better treatment strategies.
Dr. Veerasathpurush Allareddy
Dr. Brad A. Amendt
Dr. Steven Armstrong
Dr. Gustavo Avila-Ortiz
Dr. Jeffrey Banas
Dr. Banas's broad research interest is the understanding of the pathogenic mechanisms of bacteria. Much of his work has focused on the microbiology of dental caries. His lab has extensively studied how the glucan-binding proteins (GBPs) synthesized by Streptococcus mutans contribute to the development of the plaque biofilm and ultimately dental caries. Since glucan -- a polymer of glucose derived from the metabolism of sucrose -- is a primary virulence factor that propels the change in microbial ecology that leads to a cariogenic plaque, it has been proposed that proteins that have the property of binding glucan play accessory roles in this process. It is now clear that the GBPs share in structurally supporting the biofilm, each doing so in a unique manner. These studies also revealed that the relative coverage of bacteria at the substratum surface of the biofilm was correlated with the risk of caries development.

Vickerman MM, Mansfield JM, Zhu M, Walters KS, Banas JA. Codon-optimized fluorescent MTFP and mCherry for microscopic visualization and genetic counterselection of streptococci and enterococci. J Microbiol Methods. 2015 Sep;116:15-22. PMID: 26122309.

Lynch DJ, Michalek SM, Zhu M, Drake D, Qian F, Banas JA. Cariogenicity of Streptococcus mutans glucan-binding protein deletion mutants. Oral Health Dent Manag. 2013 Dec;12(4):191-9. PMID: 24390015.

Banas JA, Popp ET. Recovery of viable bacteria from probiotic products that target oral health. Probiotics Antimicrob Proteins. 2013 Sep;5(3):227-231. PMID: 23773472.

Banas JA, Biswas S, Zhu M. Effects of DNA methylation on expression of virulence genes in Streptococcus mutans. Appl Environ Microbiol. 2011 Oct;77(2):7236-42. PMID: 21841035.

Phattarataratip E, Olson B, Broffitt B, Qian F, Brogden KA, Drake DR, Levy SM, BA. Streptococcus mutans strains recovered from caries-active or caries-free individuals differ in sensitivity to host antimicrobial peptides. Mol Oral Microbiol. 2011 Jun;26(3):187-99. PMID: 21545696.

Dr. Kim Brogden
Dr. Brogden’s current area of research focuses on the ability of peptides in saliva (defensins, histatins, etc.) to serve as upstream suppressors of cytokine signaling to recombinant hemagglutinin B (rHagB) and recombinant Fimbrillin (rFimA) from the periodontal pathogen Porphyromonas gingivalis. Recently, human beta defensin 3 and histatin 5 were found to attenuate a pro-inflammatory cytokine response induced by rHagB in human myeloid dendritic cell culture supernatants and the Extracellular signal-Regulated Kinases (ERK 1/2) response induced by rHagB in human myeloid dendritic cell lysates. The mechanism may involve binding of HBD3 to rHagB and rFimA: HBD3 binds to immobilized rHagB and rFimA via surface plasmon spectroscopy and via ELISA and HBD3 inhibits binding of rHagB to cells via confocal microscopy and immunoelectron microscopy. Future research will determine the extent to which defensins can suppress early events in inflammation, an exciting concept that could be exploited to develop therapeutics to prevent or treat a variety of oral mucosal infections, particularly where inflammation plays a role in the pathogenesis of disease and its long-term sequelae.

Fischer C.L., Dawson D.V., Blanchette D.R., Drake D.R., Wertz P.W., Brogden K.A. Protein analysis of sapienic acid-treated Porphyromonas gingivalis suggests differential regulation of multiple metabolic pathways. J Bacteriol. 2015 Oct. 19, pii: JB.00665-15. PMID: 26843519.

Leelakanok N., Fischer C.L., Bates, A.M., Guthmiller J.M., Johnson G.K., Salem A.K., Brogden K.A., Brogden N.K. Cytoxicity of HBD3 for dendritic cells, normal human epidermal keratinocytes, hTERT keratinocytes, and primary oral gingival epithelial keratinocytes in cell culture conditions. Toxicol Lett. 2015 Dec 3;239(2):90-6. doi: 10.1016/j.toxlet.2015.09.006. Epub 2015 Sep 11. PMID: 26367466.

Kinn P.M., Holdren G.O., Westermeyer B.A., Abuissa M., Fischer C.L., Fairley J.A., Brogden K.A., Brogden N.K. Age-dependent variation in cytokines, chemokines, and biologic analytes rinsed from the surface of healthy human skin. Sci Rep. 2015 2;5:10472. doi: 10.1038/srep10472. PMID: 26035055.

Poulsen C., Mehalick L.A., Fischer C.L., Lanzel E.A., Bates A.M., Walters K.S., Cavanaugh J.E., Guthmiller J.M., Johnson G.K., Wertz P.W., Brogden K.A. Toxicol Lett. 2015 Aug 19;237(1):21-9. doi: 10.1016/j.toxlet.2015.05.012. Epub 2015 May 21. PMID: 26005054.

Borgwardt D.S., Martin A.D., Van Hemert J.R., Yang J., Fischer C.L., Recker E.N., Nair P.R., Vidva R., Chandrashekaraiah S., Progulske-Fox A., Drake D., Cavanaugh J.E., Vali S., Zhang Y., Brogden K.A. Sci Rep. 2014 Jan 29;4:3904. doi: 10.1038/srep03904. PMID: 24473528.

Dr. Steven Clark
Dr. David R. Drake
Dr. Drake's current research interests are focused on transmission of specific genotypes of Streptococcus mutans (SM) from mother to child in different populations. His current R01 study is looking at acquisition of SM in American Indian children from birth to three years of age. He is conducting this study in partnership with the Oglala Sioux Tribe in Pine Ridge, South Dakota. Dr. Drake has a field team consisting of dental hygienists and research assistants on site who collect plaque samples from mothers, primary caregivers, and the children. In addition, a comprehensive approach to obtain dietary and behavioral data, as well as oral health (caries assessment) is being done. The plaque samples are shipped via Federal Express to his laboratories here at the University of Iowa, where he and his research team are performing analyses on the microflora isolated from the clinical samples, with a focus on DNA fingerprinting of SM isolates. He is also involved in the R01 research on oral antimicrobial lipids led by Dr. Philip Wertz (PI) and in collaboration with Drs. Kim Brogden and Deborah Dawson.
Dr. Satheesh Elangovan
Dr. Alberto Gasparoni
Dr. Gasparoni's research interests include studying differentiation pathways in normal human oral epithelia.
Dr. Sandra Guzman-Armstrong
Dr. Guzman-Armstrong's research interests include caries disease management in adults including risk assessment, prevention and management of caries lesions at different stages.
Dr. Marcela Hernandez
Dr. Hernández is interested in adhesive systems and their relationship to dental structures; structural changes in dentin related to caries; and stepwise excavation.
Dr. Liu Hong
Dr. Lewis Humbert
Dr. Georgia Johnson
Effects of tobacco products on periodontal host response and the impact of smoking on periodontal treatment outcomes; the role of naturally occurring antimicrobial peptides in periodontal disease and clinical dental implant research.

Poulsen C, Mehalick LA, Fischer CL, Lanzel EA, Bates AM, Walters KS, Cavanaugh JE, Guthmiller JM, Johnson GK, Wertz PW, Brogden KA. Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts and dendritic cells. Toxicol Lett. 2015 Aug 19;237(1):21-9. PMID: 26005054.

Elangovan S, Brogden KA, Dawson DV, Blanchette D, Pagan-Rivera K, Stanford SM, Johnson GK, Recker E, Bowers R, Haynes WG, Avila-Ortiz G. Int J oral Maxillofac Implants. 2014-Dec;29(6):1429-34. PMID: 25397806.

Brogden KA, Johnson GK, Vincent SD, Abbasi T, Vali S. Oral inflammation, a role for antimicrobial peptide modulation of cytokine and chemokine responses. Expert Rev Anti Infect Ther. 2013 Oct;11(10):1097-113. PMID: 24124799.

Tymkiw KD, Thunell DH, Johnson GK, Joly S, Burnell KK, Cavanaugh JE, Brogden KA, Guthmiller JM. J Clin Periodontol. 2010 Nov;81(11):1613-21. PMID: 20681809.

Johnson GK, Guthmiller JM, Joly S, Organ CC, Dawson DV. Interleukin-1 and interleukin-8 in nicotine- and lipopolysaccharide-exposed gingival keratinocyte cultures. J Periodontal Res. 2010 Aug;45(4):583-8. PMID: 20337880.

Dr. Michael Kanellis
Dr. Justine Kolker
Dr. Steven Levy
Dr. Arwa Owais
Dr. Owais's research interests include prevention of dental caries in infants, toddlers, and adolescents, especially children of low income, limited access to care and high risk populations. Also of special interest to her is the medical management of caries in children, adolescents and adults. She is conducting research on silver compounds and their effect on preventing and arresting caries. Dr. Owais is a co-principal investigator of an ongoing clinical trial investigating medical management of dental caries in children using silver nitrate.
Dr. Paula Weistroffer
Dr. Jin Xie
Dr. Xie's research focuses on biostatistics and research design.