Metabolism and Cell Growth

“We are interested in exploring the complex interactions between whole-animal metabolism and cancer”

The prevalence of obesity is increasing globally. Obesity and its associated insulin resistance is a risk factor for severe health complications including type 2 diabetes and cardiovascular diseases. Furthermore, accumulating epidemiological evidence indicates that obesity also leads to elevated risks of developing several types of cancers. Conversely, cancer progression induces cachexia, a complex metabolic syndrome associated with progressive skeletal muscle and adipose tissue loss. However, the biological basis for the interactions between whole-animal metabolism and cancer remain incompletely understood.

The fruit fly Drosophila melanogaster has only recently been used as a model to study human diseases including metabolic disease and cancer, but has started to provide important insights into the biological basis and therapeutic targets of various human diseases. The ability to perform genetic screens in a whole-animal setting provides a powerful systemic approach to identify new and unexpected molecular links between whole-animal metabolism and cancer.

Using Drosophila, we developed a model system to study the link between obesity and cancer. Inducing diet-mediated obesity and insulin resistance in a Drosophila tumor model led to striking enhancement of tumor overgrowth, secondary tumor formation, loss of adipose tissues and animal lethality. We will further develop and utilize Drosophila models as useful whole-animal systems to better understand the biological mechanisms and therapeutic targets involved in these connections that can be utilized to develop preventative interventions and treatment strategies.

Metabolism and Cell Growth

Diet-induced obesity promotes tumor overgrowth in Drosophila. Ras/Src-activated tumors (labeled with GFP; green) in the Drosophila eye epithelial tissues of animals raised on a control diet (left) and a high-sugar diet (right).

Selected Publications

Hirabayashi S (2016). The interplay between obesity and cancer: a fly view. Dis Model Mech 9, 917-926.

Hirabayashi S, Baranski TJ, Cagan RL. (2013). Transformed Drosophila Cells Evade Diet-Mediated Insulin Resistance through Wingless Signaling. Cell 154, 664-675.