Research

We are motivated by Fundamental Innovations in Chemistry...

As a Chemical Biology laboratory, we have strong interests in both chemistry and biology. From a chemistry perspective, we are fundamentally interested in understanding how molecules recognize each other with specificity. Specific molecular interactions are ubiquitous in biology, including protein-protein interactions, protein-nucleic acid interactions, protein-carbohydrate and protein-lipid interactions. These seeming diverse molecular interactions are dictated by a uniform set of elementary driving forces, with hydrogen bonds, electrostatic interactions, and hydrophobic interactions as prominent examples. In addition to better understand these canonical noncovalent interactions, we are also excited to explore additional driving forces for molecular interactions, such as polar-p interactions and covalent binding mechanisms (see illustration below). We explore these novel mechanisms of molecular interaction by designing abiological or nonnatural structural motifs and evaluating their potential for enhancing the potency and specificity of molecular probes and inhibitors of biological targets.

We are motivated by Pressing Biological Problems...

Our group has a long-standing interest to better understand the mechanisms of antibiotic resistance and to test novel strategies for next generational antibiotics. In particular, we have been studying lipid modifications that confer antibiotic resistance.  Perhaps originating from our love for molecular design, we have been developing synthetic molecules that specifically recognize several types of modified lipids seen in superbugs.  Synthetic molecules as such can be potentially used to enable novel diagnosis and treatment  for difficult-to-treat bacterial infections.  Recently, through a collaboration with Professor Weerapana, we have extended our synthetic approach to biology to discover the surface proteome changes that confer cancer cell aggressiveness. 

We are motivated by Cool Technologies...

Innovative technologies such as phage display greatly accelerate the molecular discovery process.   While popular, phage display faces an intrinsic limitation: it can display natural peptides, peptides composed of proteinogenic amino acids. We and others have been developing novel strategies for incorporating designer functional groups and structural motifs into phage displayed peptide libraries.  These chemically enhanced phage libraries can offer many advantages over their natural counterparts.