We believe that one of the major challenges of modern biology is to understand the mechanisms of gene regulation and harness this knowledge to treat human disease. The importance of gene regulation in generating complex phenotypes is well illustrated by the observation that the number of protein-coding genes is almost the same in humans and nematode worms. Our lack of knowledge regarding the mechanisms that regulate gene expression in higher organisms means that we are unable to design animal models or regenerate tissue for disease treatment. We believe that currently available gene deletion and ectopic overexpression techniques do not allow us to address questions about gene regulation. Rather, we believe that an ability to control endogenous gene expression—limited to naturally-expressing cells in a gene’s physiological context in vivo—would provide us a tool that can enhance our understanding of gene function and open new scientific and therapeutic venues.
Our laboratory’s goal is to develop tools which allow conditional fine-tuning of endogenous gene expression levels. For example, we have done this through 3'UTR editing. Among other things, this tool allows us to address whether an elevation of the level of a given gene is desirable to treat a disease of interest. Recently, our laboratory received an ERC Consolidator Grant on generating improved mouse models and treatment venues for Parkinson’s disease.
Our laboratory uses genetic engineering in mouse models, accompanied by analysis at the molecular, cellular, tissue, behavioral and electrophysiological levels. We are, as a new opening, currently implementing alternative model organisms such as zebrafish model.
As a spin-off from our genetic experiments we have also recently generated a new mouse model for long-segment Hirschsprung’s disease and a new mouse model for Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) which we are currently analyzing in collaboration with Dr. Satu Kuure’s group.