Kellen Sharpe

The vast majority of small-molecule drugs used in the clinic work by binding to a particular protein and either turning it on or off. While this mode of action is ideal when disease is caused by aberrant protein function, it is not suitable when disease is caused by a missing or non-functional protein. To address this, the Burke lab has pioneered the field of molecular prosthetics, a strategy that uses small-molecules with protein-like function to replace missing proteins in vivo. In particular, we have utilized the natural products Amphotericin B and Hinokitiol as molecular prosthetics to restore ion transport across cell membranes. My thesis research aims to expand this concept to replace other functional capacities of proteins using fully designed, synthetic small molecules.