Research summary

How does Aspirin work at the cellular level?

Aspirin inhibits the production of lipid signals called prostaglandins. Prostaglandin signaling controls pain/inflammation, mediates heart health and disease, plays critical roles in fertility and development, and promotes cancer development and progression. While it is understood how prostaglandins are made and signal, and what their physiological outcomes are, it remains unclear how prostaglandin production is regulated and what are the cellular targets that mediate the outcomes of prostaglandin signaling. To address these questions, the Tootle Lab uses Drosophila (fruit fly) oogenesis or egg development as a model.

One key cellular target of prostaglandin signaling is actin. Actin forms the cytoskeleton, mediating cell shape changes and cell migration. Actin also localizes to and functions in the nucleus. The Tootle Lab found that prostaglandins are critical regulators of the actin cytoskeleton, mediating both collective cell migration and developmental events necessary for producing a high-quality egg. The lab discovered prostaglandins also regulate nuclear actin to control nucleolar activities. Finally, the lab recently found that lipid droplets, which accumulate during oogenesis, act as a source of substrate for prostaglandin production necessary for driving actin remodeling. Current research continues to build on these discoveries to:

1. Define the specific prostaglandins and their downstream targets regulating collective cell migration and follicle development.
2. Uncover the functions of, and mechanisms regulating, nuclear actin in follicle development.
3. Dissect the roles of lipid droplets in controlling cell migration and actin remodeling, both in the context of, and independent of, prostaglandin signaling

As prostaglandins, actin, and lipid droplets, as well as the processes they regulate are highly conserved, the Tootle Lab’s studies using the simple fruit fly provide key insight into the roles of these factors in development, fertility, wound healing, and cancer.

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