Sadler Lab

We use the power of zebrafish genetics to define genes required for liver growth, regeneration, cancer and response to environmental toxicants. Our research group is a diverse, integrated and collaborative team of undergraduates, graduate students, postdoctoral fellows and researchers. We pioneered using zebrafish to study liver disease, and made landmark discoveries in fatty liver disease and liver cancer using this model. We are fascinated by how cells respond to genome-wide epigenetic changes during development and how these changes promote cancer. W focus on the uhrf1 gene as this is a major epigenetic regulator best studied for its role in DNA methylation. We demonstrated that a loss of function mutant in this gene prevents liver outgrowth in embryos and unleashes transposable elements. UHRF1 is overexpressed in many types of cancer and we have shown that UHRF1 is a bone fide oncogene in liver cancer and its widespread overexpression in cancer types across tissues may point to its role in driving the global hypomethylation of the cancer genome. We are now working to dissect the mechanism by which UHRF1 drives oncogenesis and understand how senescence as a tumor suppressive mechanism is bypassed in cancers caused by UHRF1 overexpression. Our work extends to other model systems to study liver regeneration in mice and limb regeneration in octopus and other cephalopods. We use genomics and quantitative imaging in all our studies and are invested in innovating new ways to integrate data from diverse datasets.