Our research group is interested in elucidating the fundamental mechanisms of biomolecular recognition and applying the unique capabilities of biological molecules to biotechnologies. We would like to bridge the gap between understanding molecular structure-function relationships, and being able to utilize proteins/peptides/DNA for drug therapies, bioanalytics, diagnostics, and biomaterial development.
“Smart” Biotechnology and Nanotechnology We are developing new biohybrid molecular materials designed to “talk” and “listen”. These “smart” materials are designed for applications in the drug delivery and bioanalytical fields. The drug delivery group is working to develop functional and pH-responsive polymeric carriers for biomolecular therapeutics and vaccines, e.g. proteins, antisense oligonucleotides, RNA interference or silencing RNA, and DNA plasmids. Our challenge is to develop carriers that mimic the ability of viruses and pathogens to deliver macromolecules to specific intracellular compartments, while avoiding their immunogenicity and toxicity.
The bioanalytical group is working to develop smart polymer-protein conjugates, smart polymer-DNA conjugates, and smart polymer-bead conjugates as responsive molecular componentry for diagnostics, lab assays, biochips and arrays, and for upstream processing of complex fluids such as blood. We have a focus on point-of-care diagnostics, including with the Distributed Diagnosis and Home Healthcare group and in diagnostics for resource-poor settings, e.g. diagnostics for Africa.
Biomaterials and Tissue Engineering We are working in collaboration with the Biomaterials and Tissue Engineering group to develop a better understanding of the mechanisms by which materials can be engineered to control cellular responses. A primary focus is on controlling the foreign body reaction to biomaterials. To accomplish this goal, mechanistic studies of macrophage activation on biomaterials are combined with the development of controlled release systems for anti-inflammatory delivery. For the fundamental studies, signaling pathway analysis is being conducted using gene expression profiling and proteomics to identify key molecular targets for controlling cell response to biomaterials. The delivery arm of the project is utilizing new delivery systems for antisense and RNA interference therapeutics that inactivate key macrophage signaling targets or inflammatory cytokines.
Another focus area is controlling vascularization around tissue engineering matrices and tissue regeneration materials. Our work is centered on protein and nucleic acid delivery from hydrogel coatings and matrices. Similar strategies for protein growth factor and nucleic acid delivery from hydrogel matrices are being used to promote hard tissue regeneration for craniofacial and dental applications.
Molecular Recognition Studies Our applied bioengineering projects benefit from connections to more fundamental biophysical studies of molecular recognition in biology. We have two primary projects, the first in the area of biomineralization. This research is directed toward elucidating the fundamental design principles used by nature to engineer bone and teeth. We are investigating the molecular mechanisms used by proteins to control the hierarchical structure of biological calcium composites such as hydroxyapatite and calcium oxalate. These studies connect to our hard tissue regeneration applications.
The second project studies the detailed molecular mechanisms by which proteins regulate small molecule recognition. We are using a combination of site-directed mutagenesis, biophysical characterization, and high-resolution structural characterization to elucidate how proteins generate high-affinity for small molecule ligands. These studies may illuminate design principles for drug design, where high affinity is generally the desired goal. The central project is directed toward determining the structure-function relationships responsible for high-affinity and slow off-rates in the model streptavidin-biotin system. These studies connect to more applied protein engineering efforts with streptavidin, which is a widely utilized protein in diagnostics and bioanalytical technologies.