Jeeyun Chung has been named Assistant Professor of Molecular and Cellular Biology. Her lab will study how cells organize and utilize lipids for cellular functions and why their dysregulation is associated with many metabolic diseases and neurological disorders. Her goal is to build a lab environment where everyone is truly passionate about their scientific questions.
“I am a big fan of curiosity-driven research. Throughout my training, my main scientific contribution has emerged from observations that others haven’t paid attention to or underestimated,” says Chung. “By getting to the bottom of such questions, we were able to address the mechanisms of mysterious cellular events and connect them back to human physiology and disease, which can potentially provide a new perspective of therapeutic development.”
Chung began her academic journey at Yonsei University in South Korea, and completed her graduate training under Pietro De Camilli at Yale University. She went on to postdoctoral work in the joint laboratory of Tobias Walther and Robert Farese Jr. at Harvard School of Public Health and Harvard Medical School, before moving across the river to join MCB. (Don’t let her time at Yale worry you too much—when asked who she supported during The Game, she claimed neutrality and just enjoyed the day).
A simple question leads to complex discovery
A simple question as an undergraduate researcher in South Korea initiated her academic journey.
“Human telomerase that elongates telomeres acts in the nucleus but does not originate there. So how does this protein enter the nucleus and what regulates this process?” she said. “While the mechanisms of how telomerase elongates telomere had been a mainstream of investigation, I questioned about an evident fact: its predominant localization inside the nucleus. We eventually figured out this process by discovering a canonical nuclear localization signal located in the telomerase sequence and site-specific phosphorylation that regulates this event.”
This experience led Chung to be fascinated by the fact that intracellular compartmentalization of eukaryotic cells is used as one of the ways to control protein functions.
“This motivated me to study more of the field of cell biology, and eventually brought me to join the laboratory of Pietro De Camilli at Yale University as a Ph.D. student to study the function of phosphoinositides in the generation of subcellular membrane identity,” she said. “Eukaryotic cells are characterized by organelles with different functions, which are often connected by intracellular trafficking routes. How cells maintain the identity of organelles despite the constant exchange of material is a key question that his lab has been investigating.”
There, she focused on the inositol-containing phospholipid PI4P—which is a minority acidic phospholipid particularly in the membrane of the Golgi apparatus and plasma membrane in most eukaryotic cells—and its roles in controlling the intracellular distribution of lipids.
“Phosphoinositide is a minor pool of membrane lipids. But, thanks to their distinct subcellular distribution, they can confer membrane identity,” Chung said. “I wanted to know how such membrane identity can be shaped and regulated. For example, while various types of membrane lipids evidently have their prevalent subcellular localizations, most of them are synthesized in the Endoplasmic Reticulum. I was curious about how newly synthesized membrane lipids find their destinations and whether PI4P can play a role in this active lipid trafficking.”
Her graduate work produced several papers, including works discovering how PI4P is regulated to confer organelle identity of the plasma membrane and how this PI4P pool mediates non-vesicular phosphatidylserine transport at the membrane contact sites.
Her studies on membrane lipid biology sparked her interest in understanding lipid metabolism and the fascinating subcellular organelles, lipid droplets, that specialize in fat storage.
“Lipid droplets were discovered more than 100 years ago but perceived as inert fat particles for a long time and largely ignored by cell biologists,” she said. “Lipid droplets started getting a huge amount of attention and being recognized as dynamic organelles around the time I did my graduate study. I wanted to understand better what lipid droplets are and what they are doing in a variety of organisms and various human tissues.”
When she started her postdoc training in the Farese-Walther lab, she realized that studying lipid droplets is exciting but challenging since the structure of this organelle is not easily preserved using biochemical approaches. Chung teamed up with various research groups all around the world to overcome the obstacles.
“We needed innovative approaches to visualize the process of lipid droplet biogenesis and characterize molecular features involved in it,” says Chung. “We collaborated with groups that have expertise in electron microscopy, computational simulation method, mouse physiology, and structural biology. With these fun experiences, I learned the true power of interdisciplinary teamwork, and that’s one of the main reasons why I am so excited about the Harvard Cambridge campus, where I can collaborate with scientists from different research backgrounds, such as physics, chemistry, evolution, and engineering.”
During her first postdoc project on the molecular mechanisms of how lipid droplets form, she became increasingly interested in mechanisms underlying the reverse process, lipid droplet mobilization.
“If you think about it, the key to lipid droplet physiology is the cell’s ability to mobilize lipids from the lipid droplets. Increasing observations show the accumulations of lipid droplets in many pathological conditions, yet the mechanisms controlling lipid droplet mobilization and important roles of recycled fat in cellular functions remain ill-defined,” she says.
Her curiosity about the reverse process of lipid droplet biogenesis led to the discovery of the protein spartin, which is mutated in the form of human hereditary spastic paraplegia called Troyer syndrome, as a lipophagy receptor that physically bridges lipid droplets to the autophagy machinery for their degradation.
“One step further, we showed that disruption of spartin function in mouse cortical neurons causes lipid droplet and triglyceride accumulation in vivo. This result implies a contribution of lipophagy in neuronal lipid metabolism and a potential link between impaired lipid metabolism and the pathogenesis of Troyer syndrome,” she said. “It generated many exciting questions about neuronal lipid metabolism and its relevance to neurological disorders.”
Following up on this exciting new discovery, Chung’s lab at Harvard will look at the regulatory mechanisms involved in lipophagy, how the recycled fatty acids are used, and what happens when lipophagy functions well within the context of the brain versus when it leads to neurological disorders. She plans to team up with chemists and imaging experts at Harvard to visualize the famously elusive lipid droplets and manipulate their dynamics, which will increase her understanding of their function and mechanisms.
And she is excited to relocate to Harvard’s Cambridge community for her interests outside of the lab as well.
“I really love to go out to explore new restaurants,” says Chung. “Boston is good for that. There’s so many restaurants and they inspire me to develop new recipes for my cooking. During my postdoctoral training my husband and I explored the area around the Medical School and Newbury Street. Now I’m really excited about the culinary scene in the Cambridge area.” Chung also loves to garden, and is working on growing indoor avocados and pineapples—a tricky multi-year endeavor.
Throughout Chung’s educational career, she has had invaluable experience with her mentors—De Camilli at Yale, and Walther and Farese at Harvard Medical School. That has inspired how she interacts with students.
“Even though I was a young scientist, they always respected my opinions,” she says. “Such motivation coming from the mentor is one of the most important things to make mentees excited about their discovery. I want to be a cheerleader of my laboratory members and help them develop their own ideas and figure out what they want to do in their scientific careers.”
Chung hopes her lab will become known for its encouraging environment alongside scientific breakthroughs. To this end, she has already started participating in MCB’s Community Task Force on Diversity, Inclusion and Belonging.
“The important goal in my lab is to make every trainee feel safe and excited, and I believe that the departmental community could largely influence such a vibe,” says Chung. “Given that I was transitioning from postdoc to professor (and local, making it easy to participate), I thought I could bring a new/different perspective to the community for DIB efforts.”
She is a big believer in championing students and setting them up for successful scientific careers in their own rights. This is inspired by her own struggles with confidence in her academic career and observation that many who want to pursue science might choose a different career path for fear of feeling like an outsider within the lab environment.
“I have a minor disability in my hand, and this made me doubt that I could be successful in the manual aspects of biological research. My parents’ encouragement helped me to try out graduate school before giving up on a research career,” Chung says. “I realized that we cannot understand our capability without trying. Often we give up before trying due to low confidence.
My goal is to create an academic space in which each member gets confidence, can grow, support, and thrive together, later departing the lab as the next generation of scientists with brave and bold ideas that can change the world.”