Mentor:  Katheryn Rothenberg, PhD

Research:

Collective cell migration is essential for embryonic development, wound healing, and cancer invasion. In epithelial wound healing, cells migrate as a cohesive sheet, maintaining cell-cell adhesion while dynamically remodeling their cytoskeleton to close the wound. Ras-associated protein-1 (Rap1), a small GTPase of the Ras family, acts as a signaling hub that integrates upstream mechanical and biochemical cues to regulate cytoskeletal dynamics and intercellular adhesions. In Drosophila embryos, Rap1 is necessary and sufficient for rapid epithelial wound closure, promoting actomyosin polarization via Ephexin-Rho1 and E-cadherin accumulation at tricellular junctions via Canoe. However, the spatiotemporal regulation of Rap1 activity during epithelial sheet migration is unknown. Rap1 is negatively regulated by its GTPase-activating protein (GAP), Rapgap1, which stimulates GTP hydrolysis. We hypothesize that Rapgap1 spatially and temporally inhibits Rap1 activity to maintain balanced migration. To test this, we use spinning disk confocal microscopy to ablate and record time-lapse video of wound closure in stage 14 Drosophila embryos. Proteins of interest are tagged with fluorescent proteins for visualization inside living embryos, and genetic knockdown or overexpression is used to test their roles in epithelial tissue formation and collective migration. Time-lapse images are analyzed using custom-written code to extract meaningful data about adhesion formation and reinforcement, migration speed, and many other characteristics. By understanding the spatiotemporal regulation of Rap1 signaling, my research aims to uncover key mechanisms driving collective migration and identify potential therapeutic targets for improving wound care.

Publications:

• Chang J, Campbell-Hanson KR, Vanneste M...Jiang J...Kenny C. Antagonistic roles for MITF and TFE3 in melanoma plasticity. Cell reports. Apr 22 2025;44(4):115474. PMC12376229

Presentations:

• June 2025 - Poster, "RapGAP1 Negatively Regulates Drosophila Embryonic Wound Healing." HCCC Scientific Research Retreat
• August 2025 - Poster, "RapGAP1 Negatively Regulates Drosophila Embryonic Wound Healing." Biology Department Retreat
• October 2025 - Poster, Midwest Drosophila Conference, Bloomington, IN