Department of Orthodontics
Divisions of Pediatric Dentistry & Community Oral Health
The laboratory of Dr. Koo focuses on understanding the assembly principles and the virulence determinants of oral biofilms, as well as developing novel therapeutic approaches to prevent biofilm-dependent oral infectious diseases such as dental caries.
Biofilms are structured communities of microbial cells that are attached to a surface and enmeshed in a self-produced three-dimensional (3D) matrix of extracellular polymeric substances (EPS). The matrix provides an essential scaffold for the initial assembly and further development of biofilms. It promotes microbial adhesion, cohesion and protection as well as hindering diffusion. Importantly, the matrix also creates spatial and microenvironmental heterogeneity in biofilms, modulating the growth and survival of pathogens (e.g. cariogenic bacteria) locally. The matrix is considered a key factor for the existence of the biofilm lifestyle and full expression of virulence by several bacterial pathogens.
Dr. Koo’s research is particularly interested in elucidating three major questions:
(1) How the extracellular matrix assembles dynamically in 3D. In particular, he is interested in understanding the production and structural organization of EPS, and how they modulate cell adhesion-cohesion, the 3D matrix-scaffold and mechanical stability of biofilms over time.
(2) How the matrix modulates the microenvironmental heterogeneity within biofilms. Here, he focuses on spatio-temporal characterization of local pH and oxygen levels, microbial organization/positioning and gene expression in situ, and how they influence the expression of virulence of the biofilm as a whole.
(3) How to disrupt the matrix-delineated microenvironments and/or target the pathogens embedded in the matrix. He is interested in finding new anti-biofilm agents (that inhibit EPS synthesis or degrade the matrix) from plant-derived foods and organic waste products, as well as using in silico methods. He is also developing a novel drug-delivery system to target biofilm microenvironments using nanotechnology.
To accomplish these goals, his lab uses a combination of molecular, biochemical, imaging and biophysical techniques, which include enzymatic, confocal fluorescence microscopy, AFM/rheometry, transcriptomic and proteomic approaches. Several in vitro and in vivo models to study the assembly of mixed-species cariogenic biofilms are available in his laboratory. He also uses these biofilm models to evaluate the effectiveness of new anti-biofilm approaches.