Liver cancer is one of the leading causes of cancer deaths worldwide. Obesity is rapidly emerging as a significant risk factor, and the incidence of obesity is growing at an alarming rate. Although the FDA-approved sorafenib showed initial promise in inhibiting unresectable liver cancers, it is associated with many side effects. Therefore, discovery of more effective drug targets to inhibit liver cancer is needed. A protein called Id1 is highly expressed in human liver cancer samples, but its specific role in cancer initiation and progression is not known. This grant will support Dr. Ande’s studies in highly sophisticated knockout and transgenic mouse models that will uncover the specific role of Id1 in liver tumorigenesis, energy balance, and obesity-associated liver cancer. As a result, Id1 will be tested as a novel drug target to treat not only liver cancer, but also obesity-mediated metabolic disorders and liver disease.