Current Research and Scholarly Interests
Our lab uses the tools of molecular design and chemical synthesis, combined with modern molecular biology and genomics techniques, to study the biology of nucleic acids. We have a general interest in the design of small-molecule probes and reagents for the study of RNA and DNA in the cell, and of enzymes that modify them. For example, we are designing cell-permeable reagents that can be used to map structure and contacts of RNAs in living systems. We are also developing novel tools for labeling and caging RNAs, and methods for profiling transcriptome interactions. We are using these tools to uncover new knowledge about the functions of noncoding RNAs in the cell, and to study the potential of new anticancer targets in the transcriptome.
Our lab is also studying DNA repair enzymes, with a focus on development of tools that will help us measure, and potentially treat, cancer and inflammation. We design enzyme mechanism-specific fluorescent probes of DNA base excision repair, and employ them in cellular and animal models of disease. We also use these probes to discover and develop small molecule inhibitors of these enzymes, to be used in translational models of disease. We collaborate with biomedical research groups in translational studies to test our hypotheses regarding the connections of DNA repair to disease.