Xiaoguang Li
I have the great opportunity to work in the laboratory of Peter Devreotes as a graduate student. The long-term goal of our lab is to have a complete description of the network controlling migratory behavior, which will provide new targets for drugs that could be applied for cell migration. Specifically, here we identified that cells maintain complementary spatial and temporal distributions of Ras activity and Phosphatidylinositol-3,4-Bisphosphate (PI(3,4)P2) during random migration and in response to chemoattractants. Whereas Ras is active in the front, PI(3,4)P2 is distributed in a back to front gradient. In addition, depletion of PI(3,4)P2 by disruption of the 5-phosphatase, Dd5P4, or by recruitment of 4-phosphatase INPP4B to the plasma membrane, leads to elevated Ras activity, cell spreading and altered migratory behavior. Taken together, my work investigated the molecular mechanisms that bring about the mutual inhibitory interaction between Ras activation and PI(3,4)P2. These exciting findings uncover an important role of PI(3,4)P2 in the regulation of Ras activity, which may extend well beyond cell migration.
Questions & Answers
Why did you choose Johns Hopkins for your work?
Johns Hopkins is everyone’s dream school to us medical students in China. It’s a long but great academic journey to pursue graduate study overseas, and there is a strong willingness to study at Johns Hopkins. I am deeply impressed by the excellent learning resources, graduate student-friendly lab atmosphere, and supportive and enduring network of colleagues and collaborators.
What contributed to your project’s success?
First of all, comprehensive training and insightful and patient guidance from my mentor, Peter Devreotes, guided me through this academic success. Second, collaboration with some of the experts in different fields accomplished the project efficiently. For example, we collaborated with experts on the single-molecule pull-down (SiMPull) assay, the simulation using computational model, and the molecular mechanisms of my findings. The third contributions are the excellent equipment, graduate student-friendly lab atmosphere, supportive peers and enduring network of colleagues. From my side, my experimental skills, imagination, creative thinking and research experience on cell biology probably helped me a lot.
What thoughts do you have about Young Investigators’ Day itself, as a celebration of the roles students and fellows play in research at Johns Hopkins?
Recognition for the contributions of early-career scientists across disciplines is very important. Young Investigators’ Day provides students and fellows with a great opportunity to honor their work, and motivates them to pursue even higher.
What has been your best/most memorable experience while at Johns Hopkins?
I will never forget when one of the most difficult experiments finally worked out after a one-year effort on it. We were trying to design an enzyme fragment that would destroy PI(3,4)P2 in living cells. After four different constructs failed, we essentially gave up on the idea. A few months later, I decided to try some more fragments, and one of them worked out when I was making movies of the beautiful migrating cells downstairs at the microscope facility. After I changed the PI(3,4)P2 levels acutely in live cells, the cells went even crazier than I would have ever thought. I became the first person in this field who could make this enzyme fragment work in Dictyostelium cells.
Tell us something interesting about yourself.
I always make jokes to my friends that if I were not a young investigator, I would have been an artist. I enjoy painting, singing, listening to music and watching movies. I also love outdoor sports, exploring, hiking and traveling through the world.