Human Milk Oligosaccharides
As bacteria play essential roles in maintaining human health and contributing to human illness, the establishment and maintenance of a symbiotic microbiome is key to metabolic, immunologic, and hormonal homeostasis. At no time is this more important than during infancy which is a critical period of growth and immune system development. Human milk contributes substantially to the establishment of a healthy gut microbiome in breastfed infants by providing an inoculum of >400 symbiotic and commensal bacterial species and supplying components that promote or suppress the growth of select bacteria. Yet, our mechanistic understanding of how a host responds to or modulates a bacterial challenge is deficient. The central focusof this program is to define how human milk oligosaccharides (HMOs) maintain microbiome homeostasis over dysbiosis.
Fake IDs and Poisons!
The second arm of our research program seeks to apply the power of chemical synthesis to biologically relevant oligosaccharides and glycoconjugates. To enable this endeavor, we seek to develop enabling methodologies for the synthesis of carbohydrates and their derivatives. Our carbohydrate-based research program spans a range of projects, and currently includes efforts to (1) develop carbohydrate-based anticancer drugs, (2) develop improved methods to modify unprotected carbohydrates, (3) synthesize capsular polysaccharides, and (4) synthesize glycoconjugates with antimicrobial and anti-biofilm activity.
Small Molecule Total Synthesis
Our small molecule research program is focused on the synthesis of natural products which may prove clinically useful in the treatment of human diseases ranging from cancer to neurodegenerative disorders (Alzheimer’s, Huntington’s, and Parkinson’s). Our synthesis candidates have been reported to possess interesting biological activity. After chemical synthesis is complete, we employ the process of Diverted Total Synthesis (DTS) to “edit” the natural product to remove toxicity and produce congeners with enhanced potency. We leverage the core strength of Vanderbilt, carefully chosen collaborative efforts, to rigorously evaluate the biological activity of these fully synthetic compounds in vitro and in vivo.