Our research

Area 1: Site-specific bioconjugation

The development of organic reactions that can proceed under physiological conditions (in aqueous solutions at room temperature near neutral pH) have revolutionized both applied and basic biological research. These reactions have enabled the site-specific attachment of fluorophores and affinity tags to biomolecules (proteins, DNA, RNA, carbohydrates and lipids) enabling cellular imaging and pull down-based studies that have contributed tremendously towards elucidation of their roles in diverse biological processes. In addition to fundamental research, these biocompatible organic reactions have enabled the development of novel therapeutic strategies including antibody-drug conjugates (ADCs) for cancer therapy wherein tumor marker-targeting antibody proteins are site-specifically conjugated to cytotoxic anticancer agents. A major focus of our research is to develop new approaches for facile bioconjugation of proteins that proceed rapidly to form stable linkages. Bioconjugation projects in our group combine organic synthesis and protein chemistry.

Area 2: Chemical Biology of c-di-GMP signaling in bacteria

Antibiotic-resistant bacterial strains are wreaking havoc on mankind. A major reason for the development of bacterial resistance towards traditional antibiotics is that these drugs act by targeting essential bacterial cellular processes which imposes selective pressure on bacteria to evolve drug resistant strains. A promising alternative approach that would impose significantly lesser evolutionary pressure for the creation of resistant strains entails targeting bacterial virulence and regulatory pathways, rather than bacterial growth. A recently discovered signaling system orchestrated by the bacterial secondary messenger, c-di-GMP, is an attractive regulatory mechanism to target as it plays a key role in infection by regulating the formation of bacterial biofilms—complex extracellular matrices that endow bacteria with increased antibiotic tolerance (to levels ~1000-fold greater than those observed in planktonic bacteria). We are designing and testing rationally-designed libraries of small organic compounds as inhibitors of c-di-GMP signaling in bacteria and are also developing chemical tools for studying c-di-GMP signaling in bacteria.

Area 3: Concise routes to complex heterocycles

Substituted heterocycles display rich pharmacological profiles and biological activities, and are therefore attractive scaffolds for drug design. We are developing facile routes for the synthesis of polysubstituted derivatives of heterocycles such as pyrazoles, oxazoles, and piperidines.