Research objectives 2018 update: My goals are (1) to develop peptide-based therapeutics against multidrug-resistant pathogens, (2) to investigate the impact of environmental toxicants/antimicrobials on the microbiome, and (3) to develop a global health program in Haiti (microbiome, combatting infections, etc.)
Research objectives 2018: I have a multidisciplinary expertise in antimicrobial therapeutics, microbiology, biochemistry, immunology, toxicology, and pathology. This extensive experience enables me to address two different (although related) problems: multidrug resistance and the impact of antimicrobial therapeutics on the microbiome.
I have investigated the structure-function relationship of antimicrobial peptides (AMPs) using de novo-engineered cationic AMPs (eCAPs) and demonstrated that AMP structure could be optimized to overcome many of the limitations of natural AMPs (e.g., reduced activity in acidic pH and serum salt concentrations). I initially enhanced the design of an initial series of Montelaro-engineered AMPs and demonstrated systemic efficacy against P. aeruginosa, using animal models of in vivo toxicity and sepsis treatment. The data led to six first-author papers in addition to over a dozen collaborative publications. Despite the success of these eCAPs, this was the first trial of optimization of the engineered AMPs, and these peptides are still being engineered mostly through trial and error. Considerable effort is required to completely investigate the potential of this new source of therapeutics. However, my vision goes far beyond the development of AMPs as antimicrobials as described in the following aims.
Aim 1. To establish a rational framework for the design of peptide-based therapeutics. We need to establish a rational framework for peptide design for specific clinical applications against multidrug-resistant pathogens. I will expand AMP engineering to the design of peptide-based therapeutics of enhanced pharmacological properties with the goal to overcome hard-to-treat bacterial infections as well as viral and cancer disease. To be continued/updated…