An NCI-designated Comprehensive Cancer Center
By Maxine Nunes | October 17, 2018
When Li Li, a Ph.D. candidate at City of Hope, was an intern at Taishan Medical University in China, she came to a heartbreaking realization.
“I saw that when it came to helping patients, doctors often had no answers. And overcoming those limitations required research,” she said. “So after careful thinking, I knew that was the field I wanted to pursue.”
Her decision involved a bigger change than simply switching careers. If she wanted to be involved in the most cutting-edge research, she would have to leave her native China for the U.S.
Thanks to that decision, which led her eventually to City of Hope, we are now closer to finding an effective treatment for the neurodegenerative condition, Alexander disease.
Under the supervision of Yanhong Shi, Ph.D., director of the Division of Stem Cell Biology Research, Li designed and developed a groundbreaking study that was published in August in the journal Cell Stem Cell.
Her work with Alexander disease may also shed new light on similar neurodegenerative conditions such as Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis (ALS).
What these diseases have in common is the decreased production of myelin, a substance that forms a sheath around certain nerve fibers. When this sheath is inadequate, it interferes with the transmission of nerve impulses and brain functions.

Discovering the Mechanism that Causes Myelin Defects

Myelin is produced by cells called oligodenrocytes, and when their functions are suppressed, myelin production decreases. However, the mechanism that caused the suppression had not been identified — and that’s what Li set out to find.
She chose Alexander disease for her study because myelin suppression is its primary defect — but to study it she had to overcome an obstacle researchers had faced in the past. Animal models for this disease were unable to exhibit the myelin loss found in patients, and taking human brain samples was too invasive.
The solution, Li thought, might be found by using a Nobel Prize-winning discovery she had worked with to earn her master’s degree, induced pluripotent stem cells (iPSC). Like embryonic stem cells, iPSCs are able to generate any type of cell in the human body — but with one great advantage. They can be reprogrammed from adult cells, often from the skin or peripheral blood.
“I was really amazed by these cells,” she said, “and I came to City of Hope to explore more about them.”
To overcome the problem that had hindered research in the past, Li used iPSCs to create a stem cell model of Alexander disease. This allowed her and her team to identify a protein marker in mutated cells called astrocytes that suppresses the production of oligodenrocytes and myelin — the mechanism scientists had been searching for.
The next stage of their research will involve finding a medication that can reduce the level of the protein identified in this study and thereby restore myelin production.
Though Alzheimer’s, Parkinson’s and ALS diseases are more complex than Alexander disease, the same mechanism is likely to cause myelin suppression — and its discovery may soon bring new hope to millions who suffer from these conditions.
That’s quite an achievement for a student who hopes to receive her PhD next year.

Another Discovery — How to Balance Life and Work

Li is also married and the mother of an 8-month old baby girl, so finding the balance between work and her personal life can be tricky. But she thinks she’s hit on the answer.
“Wherever you are, be there,” she said. “When I’m at work, I’m totally focused on work and when I’m at home I’m very devoted to having fun with my family.”
And if you’re wondering about her name, we asked.
“Yes, Li is my first name and also my last name. They’re different words in Chinese, but in English they’re the same.”