Defining the peroxisome-lipid signaling network in innate immunity.

Organisms need an efficient and tightly controlled immune system to defend against infections and cancer. Recently, scientists discovered that immune cells change their "font of energy" and the way they use and transform it (metabolism) to augment the fight against an immune challenge. Peroxisomes are structures found in every cell that control important processes in metabolism. We found that peroxisomes are central regulators of an organism's immune system. Peroxisomes in immune cells are important for producing and managing molecules like "fats" and hydrogen peroxide that are needed to turn on or off immune responses such as the engulfment of invading microbes or cancer cells. Our discovery added a previously unknown contributor to the growing number of cellular "players" that control the immune response. Knowing how the immune responses function is quintessential to understand the mechanisms of diseases of immune disorders and to find new and more effective cures. We use the fruit fly as a model system in our studies to dissect the mechanisms of diseases. We use the fruit fly because their genes can be easily manipulated and they have basic cellular processes, including aspects of immune defense, that are similar to those in humans. Thus, studies in fruit fly can help us to quickly define the mechanisms by which peroxisomes function during systemic immune responses and then transfer our discovery to human health. Our research program aims to define 1) how peroxisomes contribute to changing metabolism in immune cells to activate their "defense mode' during microbial challenge; 2) how immune cells use "fats" to control an organism's way to fight an infection; and 3) how conserved in mammals are the mechanisms and pathways found in fruit flies, so that we can exploit peroxisomes as a disease marker for immune disorders and as therapeutic targets for new and more efficient drugs to treat patients with immune deficiency, autoimmune disease and cancer.