What we do:
The Kohli Lab started in 2010, as we had just come off a decade marked by tremendous advances in genomics, marked by the sequencing of the human genome and pioneering methods that offered access to troves of DNA sequence information. Against this backdrop, the lab was inspired to understand not simply what information is encoded in genomes, but how this information changes. Our motivation for studying the ‘dynamic genome’ is rooted in its relevance to biology and medicine. Affinity maturation of antibody responses, epigenetic transformations promoting cancer, or the acquisition of antibiotic resistance – representative processes that shaped the disease course of patients – all involve modification or mutation to the genome. Our lab is grounded in enzymology and chemical biology, and aims to understand how enzymes can purposefully target and modify the genome. To this end, our lab has focused on major classes of mammalian DNA modifying enzymes and on the diversity-generating mechanisms at play in bacterial pathogens. As our work deciphering natural processes that reshape genomes advanced, our lab has recognized that mechanistic insights into these processes can also open up new frontiers in biotechnology, allowing us to exploit and target these enzymes to read, rewrite, or erase genomic modifications. These three areas drive the bulk of past and ongoing study in the lab.