Metabolic deregulation, largely associated with loss of the energy stress sensor AMPK, has become appreciated as a significant risk factor for hepatocellular carcinoma (HCC). HCC is a deadly cancer with very few effective treatments for the advance stages and is increasingly prevalent in Texas, in part due to a high rate of obesity and non-alcoholic fatty liver disease. The high incidence and mortality rates of patients with HCC emphasize the necessity for both understanding the etiology of HCC and developing preventative therapeutics against HCC.

While previous studies have uncovered a correlative role for AMPK activation in HCC, neither the functional role of AMPK in HCC prevention nor the...

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Metabolic deregulation, largely associated with loss of the energy stress sensor AMPK, has become appreciated as a significant risk factor for hepatocellular carcinoma (HCC). HCC is a deadly cancer with very few effective treatments for the advance stages and is increasingly prevalent in Texas, in part due to a high rate of obesity and non-alcoholic fatty liver disease. The high incidence and mortality rates of patients with HCC emphasize the necessity for both understanding the etiology of HCC and developing preventative therapeutics against HCC.

While previous studies have uncovered a correlative role for AMPK activation in HCC, neither the functional role of AMPK in HCC prevention nor the ability of AMPK activation to prevent HCC have been fully elucidated. I plan to establish my laboratory at BCM with the long-term goal of defining the relationship between metabolic disease and cancer to uncover novel therapeutics for cancer prevention. We will focus on evaluating the role of the metabolic sensor AMPK in the prevention of hepatocellular carcinoma.

Our initial goals are to define the role AMPK in hepatocellular carcinoma using genetic loss and hyperactivation of AMPK in the liver, and to determine the therapeutic role of AMPK activation for the prevention of HCC. Through this work, we will achieve a greater understanding of the underlying biology of HCC related to metabolic disorder and generate new avenues for HCC prevention. In addition to yielding novel insights into the basic mechanism of AMPK in HCC, this framework will provide a new paradigm for studying other cancer types where metabolic deregulation plays a critical role in the development and prevention of cancer.

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