Yukiko Yamashita

In life, there isn’t much that outranks the importance of pursuing truth—or so says Yukiko Yamashita. As a budding scientist in Japan, Yamashita put her philosophy into practice, earning a PhD in biophysics at Kyoto University. After capping off her degree, Yamashita continued her studies in the U.S., joining Margaret Fuller’s lab at Stanford University as a postdoctoral fellow. There, she found a new fascination: stem cells.

Yamashita focused her early research on stem cell division, a process in which a stem cell produces two daughter cells: one that’s a copy of itself and one that’s differentiated, set on a path for a particular cell fate (a heart or sperm cell, for example).

The process requires a delicate balance. Too many stem cells could lead to cancer, while a lack of differentiated cells might result in tissue deterioration. Yamashita became intrigued with the question of how cells maintain that harmony. What determines whether a daughter cell reflects its parent or assumes its own identity?

As a postdoc, and now as an HHMI investigator at the University of Michigan, Yamashita has made transformative contributions centering on this question. She showed, for instance, that stem cell division is asymmetric (resulting in two cells that are not identical) due to the inheritance of a key structure in the cell, called the centrosome. The daughter cell that retains the original copy of the mother cell’s centrosome remains a stem cell, while the daughter cell that receives a duplicate copy will later differentiate. What’s more, she found that the cell implements its own precautionary measure to maintain the correct stem cell–to–differentiated cell ratio—a “checkpoint” that monitors the correct centrosome orientation. If the centrosome is positioned incorrectly, the cell’s division cycle comes to an abrupt halt, stopping the would-be faulty division.

Yamashita and her group also study how stem cells communicate within special microenvironments, called niches. The group recently discovered a thin, microscopic thread, called a microtubule nanotube, that helps facilitate signaling between stem cells and other cells in the niche. Work from Yamashita’s lab suggests that these long tendrils play a critical role in supporting communication to ensure successful stem cell self-renewal and differentiation of daughter cells.

Image: Tony Ding

About the HHMI Investigator Program

HHMI investigators, appointed through rigorous competitions, are among the most creative and promising biomedical researchers in the nation. Scientists receive long-term, flexible support, enabling them to follow their own curiosity in the pursuit of answers to significant biological questions. The Investigator Program is the Institute’s flagship program, with an annual commitment of more than $600 million dollars to support the investigators and their host institutions across the United States. The collaboration between HHMI and these institutions powerfully expands the nation’s research capacity. Read more >>