Every second, mitochondria—the microscopic powerhouses of our cells—fuse, break apart, and reorganize. They manage energy, detoxify waste, and shape how cells behave. But what if these tiny structures did more than power life? What if they helped decide what kind of life a cell becomes?
That’s exactly what Dr. Chun Ju Chang and her collaborators proposed in a 2019 study published in Cell Metabolism. Their findings revealed a direct link between mitochondrial dynamics and the identity of stem cells—offering a new lens into cancer progression and regeneration.
“This was a missing piece,” Chang says. “We knew mitochondria mattered. But we didn’t know they could actually direct the fate of a dividing stem cell.”
A scientific career built across borders
Chang’s journey to this discovery spans decades and continents. Born and raised in Taiwan, she later completed her Ph.D. at UCLA and postdoctoral training at the University of Texas MD Anderson Cancer Center. With stops at Roswell Park in New York and now a professorship at China Medical University in Taiwan, she has pursued questions at the intersection of cancer biology, cell signaling, and drug discovery.
Across these roles, she has received over a dozen recognitions, including the Amgen Award in Basic Science Research and the Women in Cancer Research Scholar Award. But her most meaningful contributions often appear in the achievements of her students.
“I believe mentoring is how science continues,” she says. “When a student understands not just how to do an experiment, but why it matters, that’s a win.”
Linking EMT, mitochondria, and stem cell fate
The 2019 study focuses on a cellular process called epithelial-mesenchymal transition (EMT). EMT is known for its role in cancer metastasis, allowing cells to detach, move, and invade new tissues. But EMT also grants cells some stem-like traits, which can make tumors harder to treat.
Chang and her team found that EMT causes mitochondria to fuse—forming long, tubular structures rather than fragmented ones. This change is not just structural. It increases antioxidant capacity and promotes self-renewal in mammary stem cells. The fused mitochondria, they discovered, are directed into at least one daughter cell during stem cell division, helping preserve a pool of renewing stem cell population.
At the heart of this process is MFN1 (Mitofusin 1), a protein required for mitochondrial fusion. The study showed that MFN1 doesn’t just regulate mitochondrial shape. It also interacts with polarity proteins like PKCζ and NUMB, guiding how the fused mitochondria are split during cell division.
“When MFN1 was knocked down,” Chang explains, “cells lost that polarity. Both daughter cells got the same mitochondria, and stemness was reduced.”
Why this matters for cancer
This finding has significant implications. Cancer stem cells are thought to drive recurrence and resistance. If fused mitochondria help sustain those cells, then targeting mitochondrial fusion—particularly MFN1—could be a way to make tumors more treatable.
More broadly, the study challenges assumptions about what drives stemness in cancer. While transcription factors and signaling pathways are well-known players, Chang’s work shows that the physical state of organelles also plays a critical role.
Her team even demonstrated the effect in vivo using genetically modified mice. Deleting miR-200c, a microRNA that limits MFN1, caused excessive mitochondrial fusion and an increase in stem cells in the mammary tissue—linking EMT, mitochondrial behavior, and stem cell expansion at the tissue level.
From the bench to the classroom
Despite the complexity of her findings, Chang is passionate about making science approachable. As a professor at China Medical University, she emphasizes hands-on learning and encourages students to challenge assumptions.
“I always tell them, don’t just read the conclusion. Ask how they got there” she says.
In class, she breaks down advanced concepts in cell signaling and metabolism with visual models and analogies. In the lab, she helps students design clean, logical experiments—often challenging them to predict outcomes before touching a pipette.
“She makes you think in terms of mechanisms,” one former mentee said. “Not just what’s happening, but why.”
Mentoring with intention
Chang credits her own mentors at UCLA and MD Anderson for showing her the value of rigorous but supportive training. Now, she strives to pass that on—especially to young women entering cancer research. She advocates for greater representation in leadership and speaks often about the structural barriers women face in academia.
“It’s not just about seats at the table,” she says. “It’s about making sure people are heard once they’re there.”
The next question
Today, Chang continues to investigate how mitochondrial dynamics affect cell fate—and how these insights might be leveraged in therapy. Her recent work explores whether disrupting MFN1 interactions could selectively deplete cancer stem cells, or whether boosting mitochondrial control might improve regenerative medicine.
She’s not done asking questions.
“As scientists, we don’t always get neat answers. But we get clues. And when the clue leads somewhere new, we follow.”
Interview with Chun Ju Chang
What inspired you to look at mitochondria in the context of stem cell polarity?
When we think about mitochondria, we usually focus on energy production. But I was always curious whether their structure could actually influence how cells make decisions. The link between mitochondrial dynamics and stem cell fate hadn’t been fully explored, so we asked a simple question: what happens to mitochondria when a cell starts to change its identity?
In your study, you found that EMT triggers mitochondrial fusion. Why is that significant?
EMT is a process involved in cancer spread, but it also gives cells stem-like properties. What we discovered is that EMT doesn’t just change how cells move—it also alters their internal architecture. Specifically, it causes mitochondria to fuse, which boosts the cell’s ability to manage stress and divide asymmetrically. That’s a big deal because asymmetric division is one way cells maintain a stem cell pool.
What role does MFN1 play in this process?
MFN1 is a fusion protein, but we found that it does more than just reshape mitochondria. It actually interacts with other proteins that guide cell polarity—like PKCζ and NUMB. That interaction helps mitochondria get sorted into one of the daughter cells during division. So MFN1-polarity protein interaction becomes a kind of bridge between organelle dynamics and cell fate decisions.
Did anything surprise you during this research?
Yes—the extent to which mitochondrial shape impacted stemness. When we induced EMT, mitochondria became highly fused. That shift told us we were looking at a new link.
You’ve worked across the U.S. and Taiwan. How have those experiences shaped your approach?
They’ve made me value both independence and collaboration. In the U.S., I trained in large research centers with a strong focus on translational impact. In Taiwan, I’ve focused more on mentoring and building collaborative research capacity. Both are important. Science doesn’t move forward in isolation.
What advice would you give to a student interested in cell biology and cancer research?
Stay curious. Learn how to ask the right questions and design clean experiments. And remember that some of the biggest discoveries come from small observations. Mitochondria were once just the background of our images. Then we looked closer.
