MD, PhD - Washington University in St. Louis
Research Description
The digestive system executes numerous, complex, well-coordinated tasks to mediate metabolism, gastrointestinal motility, nutrient absorption, and waste excretion. Proteins implicated in normal gastrointestinal physiology or disease states have been coopted or targeted to generate protein-based therapeutics. Yet, development of luminally-acting protein-based therapies remains challenging due to (i) inherent limitations in drug stability or delivery that arise from peptide and antibody scaffolds, (ii) limited exploration of protein designs, and (iii) harsh conditions imposed by low pH and protease activity within the gastrointestinal environment. Miniproteins represent an emerging class of drug scaffolds that, given their length of 30-80 residues, are perfectly suited for the design, screening, and optimization of target inhibition/activation, proteolytic stability, and tissue penetration. Vasilios's research will leverage recent advances in computational protein design with generative artificial intelligence and nucleic acid-based display methodology to develop novel miniprotein-based therapeutics for luminal gastrointestinal disorders.
