Fred Hutchinson Cancer Research Center postdoctoral fellow Dr. Siqi Li has been named the Mark Foundation for Cancer Research Fellow, one of thirteen 2022 Damon Runyon Fellows. The four-year, $231,000 fellowship will provide Li a stipend to support her investigations into the interactions between mutated cells and their normal neighbors that could affect tumor growth.
The Damon Runyon Cancer Research Foundation awards these fellowships to encourage the nation’s most promising young scientists to pursue careers in cancer research, according to the foundation’s press release. Li is tracking cancer to its earliest origins.
“I'm particularly interested in the early stage of cancer initiation, when the cells are potentially physiologically normal,” said Li, who is mentored by Hutch cancer geneticist Dr. Slobodan Beronja. “What's actually occurring within the mutated cells? And how are the surrounding cells responding to that?”
Interactions between a mutated cell and its normal neighbors can spur or rein in tumor development and growth, and Li wants to figure out how. Li hopes her findings provide a deeper understanding of the earliest forces shaping tumor formation, and also help pave the way for the development of cancer-preventive therapies that take advantage of our body’s natural processes.
“Siqi is tackling a very complex and challenging biological problem in a physiologically relevant context and an unbiased and functional manner,” Beronja said. “What she uncovers will likely lay a foundation for an exciting research program of her own. I am incredibly proud of her for putting together such a competitive proposal and expect it will give her the early recognition and support for what will no doubt grow to be a successful academic career.”
How tissues handle mutations
Mutations, changes to the letters of our DNA alphabet, accumulate in cells all over our body. Many of these are known cancer-driving mutations.
“Yet those tissues are still physiologically normal, suggesting that there is a way for a healthy tissue to fight back against these mutations, and protect itself,” said Li, who works with skin cells.
Beronja’s team has uncovered several such cancer-fighting processes, showing that normal skin stem cells can respond to mutated neighbors in ways that prevent tumor formation.
Skin stem cells maintain skin tissue by producing skin cells with specialized functions, a process called differentiation. But fully differentiated skin cells don’t divide. Skin stem cells balance this by self-renewing, producing more skin stem cells. Healthy skin balances stem cell renewal with differentiation. Too much differentiation depletes the well of stem cells, but too much self-renewal prevents skin from building its layers and can help promote the overgrowth associated with cancer.
Previous work by Beronja’s group showed that certain cancer-promoting mutations in an individual stem cell can upset this balance, pushing the cells to renew or differentiate more than normal.
“But the surrounding [normal] stem cells will have the opposite behavior,” Li said.
For example, when some mutations prompt skin stem cells to ramp up their self-renewal, normal neighbor stem cells bring balance back to the tissue by differentiating more. Other mutations seem to trigger a form of cellular peer pressure: when mutated skin stem cells differentiate more, their unmutated neighbors differentiate less — and mutated cells eventually get pushed out.
Li aims to outline the molecular signals from mutated skin stem cells that affect their normal neighbors and uncover the molecules that those neighbors use to sense and respond to the mutants.
Her Damon Runyon award will support her as she builds on experimental approaches in the Beronja Lab that enable scientists to study how specific genetic changes impact skin cells. Li will develop new techniques to screen for the molecules involved in communication between normal and mutated skin cells. She will also develop a noninvasive method to track and study these cells and their interactions in mouse skin.
The rewards of the fellowship go beyond supporting her experiments, however, Li said. She looks forward to the opportunity to exchange ideas with fellow awardees. And the fellowship offers her an extra level of autonomy as a young scientist.
“It will allow me more independence as a researcher,” Li said. “I’ll have more control over the directions of my project. It will be key for carving out my niche as a scientist.”
