Dr. Lucy Erin O’Brien is an Assistant Professor at Stanford University in the Department of Molecular and Cellular Physiology. She received a BA in Biochemistry at Harvard University and a PhD in Biomedical Sciences at UCSF. As a postdoc at UC Berkeley (David Bilder’s Lab), she sought new expertise in Drosophila (fly) genetics, development, and stem cell biology. Her research established the fly midgut as a powerful system to study cell and tissue dynamics through imaging-based quantitative analysis. Additionally, her work first demonstrated that midgut stem cells exhibit regular symmetric divisions in addition to asymmetric ones, setting the stage for her current studies. Dr. O’Brien is also a big fan of the outdoors. Before she went to UC Berkeley, she spent three years skiing and kayaking, on personal trips and as an instructor.
The focus of Dr. O’Brien’s research is to understand how stem cells adaptively sense and respond to the changing needs of the organs they support. Over an animal’s lifetime, individual organs can maintain constant size, grow, or shrink, all as part of normal physiology. Organ maintenance, growth, and shrinkage each require precise, yet distinct, types of stem cell division behaviors. However, little is known about the different mechanisms that underlie these distinct behaviors. During her seminar at the Buck Institute, she talked about the adaptive growth of stem cells — stem cells drive a reversible, food-induced growth response through specialized divisions. When flies start to eat, their intestinal stem cells respond to increased food intake by producing more intestinal cells, thus expanding the size of the gut. When food is taken away, the size of their gut shrinks. The reason for this phenomenon is that the intestine is capable of secreting its own insulin to control its own adaptation. The Drosophila Insulin-Like Peptide 3 (dILP3) is expressed in gut visceral muscle upon feeding and signals directly to adjacent stem cells, activating proliferation and growth. She also demonstrated homeostatic renewal of stem cells and progress toward developing whole organ live imaging of the midgut.
Q: It is very interesting to see that the guts of fruit flies can grow 4 times bigger when they are fed. Does this phenomenon also apply to humans?
LO: We don’t know about humans at the same resolution that we do in flies. But what we do know, for instance, is that humans who cannot consume food normally have shrunken intestines. And this effect is not just due to food or no food, but also due to how food gets delivered.
Q: You found that insulin signaling is a big driver of the adaptive growth of intestinal stem cells. Does this research have impact on diabetes or other metabolic disorders?
LO: Yes. It is very intriguing to think about the possible applications. I’m not currently aware of a direct application, but we know that bariatric surgery (weight loss surgery) can cure diabetes very quickly. You can imagine that there are some kinds of signaling from the gut that affect diabetes. Right now our goal is to define on a cell biological level, how gut cells are working, what controls cell division, cell death and cell fate. And then we want to come back to understand how the adaptive growth happens.
Q: Can you talk a little more about the connection between stem cell dynamics and aging?
LO: For example, we know that stem cells become dysfunctional with age. So understanding how exactly they become dysfunctional will help us to understand the aging process. Also, if at a basic molecular level, we really understand how to manipulate stem cell homeostasis or dynamics, that would open the door for developing new ways to make therapies for rejuvenation. The Buck Institute has so many great examples of people who study stem cells during aging, like the Jasper lab.
Q: I noticed that before you went to Berkeley for your Postdoc, you pursued a complete different path. You were a full-time skier and kayaker for a couple of years. Could you tell us why you did that and what brought you back to science?
LO: Growing up I was very much in the “Ivory Tower”. You know, always studying. But when I moved to California for grad school at UCSF, I started discovering the ocean and the mountains. At some point in grad school, I had this crazy idea that I wanted to be an outdoor bum for a few years after grad school. Because when else can you do it? Not as a postdoc or as a faculty. Maybe if you are on a sabbatical, but I don’t know if I want to throw myself down steep mountains at that age.
Q: So when you left science you already knew that you were going to come back?
LO: Yes. I knew that I wanted to come back when I left. I just didn’t know exactly when. But I remember one winter in the mountains, I started feeling that “Ok, this is fun. But it is only fun for you. You are not doing anything to give back to society. You are not helping anybody else.” So I started to feel really selfish. And that’s when I knew I was ready to come back.
Q: Do you still spend a lot of time outdoors? How do you balance your research life with your personal life?
LO: I do much less than I used to. But I still try to go surfing a few times a month in the summer and fall. I do more cycling because it’s easy to fit into a busy day. I have to say that balance is not the word that I think about. It is important to me to be passionate about science and about things outside of science. When things in the lab are particularly hard, it’s nice to have a place that you can go to, where it doesn’t matter what the results of the experiments are or what happens to your paper. I also have a group of friends who aren’t scientists. They help me keep everything in perspective. And then I come back to science and have renewed energy and excitement.
Q: Can you talk a bit about what it’s like to be an Assistant Professor?
LO: I have been in this position for two years now. Still, I’m continually amazed and inspired, every day. It’s exciting to have the chance to create a team and environment where incredible things can happen. It seems there is always “a first” of something happening in our new lab. One thing that’s amazing is instead of having just “my project”, I’m a part of many different people’s projects. I get to hear the cool ideas they come up with and work on these ideas with them. A down side is that there is little time to do experiments on my own, and I miss the hands-on part.
Q: What advice would you give to those who want to pursue academic career?
LO: One helpful analogy for me has been the time I’ve spent in the mountains. If you are trying to get to the summit, it’s almost never the case that there is only one route. There are usually many different routes, and for whatever reason, one route might work for someone and another route might work better for someone else. And even if you think, “this route is not going to work, I’m going over here instead”, sometimes you discover a new path or opening that you never knew existed. This was a really powerful idea for me, because my decisions have not always seemed like the best “career” choice at the time. But things have a way of working out. If the science really speaks to you, you will do it well. You will come up with the great ideas, the important questions. You will find something in it, because it means so much to you.
For more on Dr. Lucy O’Brien’s exciting research, check out the O’Brien Lab website.