Interviewing Dr. Asuka Eguchi

By Addison Evans, Head Journalist 

I recently had the opportunity to interview Dr. Asuka Eguchi, a post-doctoral fellow in the Blau Lab at Stanford University. In college, Dr. Eguchi attended the University of Alabama in Huntsville. For graduate school, she went to the University of Wisconsin-Madison and received her Ph.D. in Cellular and Molecular Biology. She has performed groundbreaking research including her current work on heart failure in Duchenne muscular dystrophy.

She is the perfect example of a woman in STEM who works incredibly hard. Her research proves how much of a hard worker she is. Although she is a woman in STEM, that doesn't discourage her from doing what she is passionate about.  

When did you show interest in biology and STEM?

It wasn’t until college when I realized that you can do research in science. In middle and high school, I was good at math but it didn’t dawn on me that there are people in research labs that do this for a living and think about designing therapies for patients. In college, I got the opportunity to work with neurons and study these neurodegenerative diseases. It was just getting my foot in the door and at first, I was doing really simple things like washing dishes. I very soon got exposed to cell culture. It was thrilling to me to work with cells that are constantly dividing and then sensing the environment. We would expose them to certain stresses and realize that the neurons were much more sensitive than the other types of cells that kind of wrap around the neurons. We would enhance the communication between the neurons to see a different sensitivity to stress. Seeing this made me eager to learn about what other avenues you could look into. Right around this time, there was a breakthrough where you could make stem cells out of any cell type in the body. Now, what’s typically done is you take a blood draw because it’s easy and then you isolate all the cells that have DNA. You can use those cells to make stem cells that can become any cell type. That was just mind-blowing to me and I knew that I wanted to get in on that type of research. That’s kind of how my career trajectory began. In grad school, I studied the process of making stem cells. Now, in my postdoctoral work, I’m using those types of stem cells to make heart cells and then compare healthy and disease states. 

Did you ever consider majoring in something different in college or taking a different path?

In the beginning, I was focused on becoming a doctor or a nurse but as soon as I began doing research, I was hooked and realized that I could become someone like my mentor who is a professor running her own lab. Then, I became focused on “What are the next steps to get there?” Trying to figure out what I wanted to do happened super quickly during my freshman year of college.

Did you have any family members or friends that you saw who inspired you to have a STEM-related career?

I was definitely encouraged a lot in college so that was helpful. In terms of my family, I’m a first-generation college student. I didn’t come from a very academic family but in college, I was inspired by the other professors who were doing research. I felt very encouraged by them to keep pursuing my interests because they felt that I could make an impact. Having their support was something I valued.

Do you notice a gender gap in your field?

Yes. Where fewer women happen is in getting good opportunities and resources. The further you go into science, academic, and pharmaceutical science, where you go into industry and develop drugs and then medical professions as well: The higher ranked people are essentially very male-dominated. It’s hard sometimes to get fewer opportunities, to present at conferences, or to get funding opportunities. If your male colleagues are getting more than you yet you’re expected to be as productive or publish high-impact science like them, it’s challenging to deal with that. There’s a lot of work to be done to really collapse that gender gap. 

Does that ever discourage you to see that your field is male-dominated and that you have to work twice as hard?

Yes, it can be discouraging. I think what’s important to do is surround yourself with positive people and try to focus on your work and not so much on all the hurdles. If you let it weigh you down, then it is hard to push and focus on your work. Focusing on little wins at a time is vital. To make a change, you have to be a leader and you have to be someone who has the power to make the changes. As a student or in my career, where I’m at now, I don’t have the power to make systemic changes on how resources are distributed. You can try to use that to motivate yourself and to be like, “I want to be the source for change so I’m going to try to make it.” 

Can you describe your work with artificial transcription factor (ATF) libraries and how they affect cells?

In grad school, I was focusing on making stem cells out of a cell type that wouldn’t normally become any cell type in the body. I was also interested in making genes turn on. In order to change cell fate, you have to turn on a special set of genes. Sometimes, we already know this recipe of which genes to turn on to make a specific cell type. For example, there are recipes for heart cells. We can do that pretty efficiently now. There are other cell types that are difficult to make and we don’t have good recipes for them. I made a library, which just means that it’s like a collection of all these different proteins that can turn on genes at random. You don’t know which genes they’re going to turn on because they’re binding random base pairs. In my case, it was a 9-base pair library. Any 9-base pair sequence in DNA, in the genome, it could target. Then I would see if it changed into the cell type that I was interested in. I did these types of screens where I made these skin cells into stem cells. Sometimes I made stem cells into heart cells, in more of a reverse direction where you restrict the cell type. It all came from this collection of random proteins. It’s unique in the sense that you have a bag of solutions to the problem. You test out all these random solutions and then find out which ones answered your question. Then you go back to the cell and ask, “What was the solution?”. Then it gives you an idea of “Oh well these genes turned on so that’s what’s important for the cell type.”

It is of my understanding that you have lots of knowledge in Duchenne muscular dystrophy research. Can you go more in-depth into that? 

Duchenne muscular dystrophy (DMD) is a disease that affects boys because the gene that is missing or is problematic in these patients is on the X chromosome. Girls have two X’s so even if one gene has a mutation, the other gene is usually healthy. The healthy copy compensates so we don’t typically see this disease happening in girls. It’s a severe muscle wasting disease so it causes patients to have major problems with their muscles and that includes skeletal muscle but also the heart and the diaphragm. It’s a really sad disease because, by the age of 13-15, these boys are in wheelchairs. They start to have problems breathing and then they have problems with heart failure in their 20s. I’m focusing on the heart and how we can study how their heart cells are behaving in a dish and then try to come up with gene therapy strategies to help delay the onset of heart failure. The protein is really large and it’s really hard to deliver to these patients. The current technology is to use this delivery method called adeno-associated virus and usually, we’re scared of viruses because they make us sick. This virus contains DNA that you can engineer so you can make it a therapeutic virus where it’s just a mechanism for it to enter your body. The problem with the adeno-associated virus is that it is really small in its capacity to deliver genes. It can deliver small genes but not large genes. The packaging size is ⅓ the size of the full-length gene that is missing in Duchenne patients. It’s kind of tricky to figure out how you can use that system to try to deliver therapeutic approaches.

Is anyone developing gene therapy for other symptoms that are occurring in Duchenne patients?

There are already 3 clinical trials ongoing on gene therapy. They’ve tried to miniaturize the gene so that it has some of the more important components. Before it goes to a clinical trial in patients, a lot of research is done in the lab using mice. In the mice, these smaller versions of the protein that’s missing in Duchenne patients helped them with their skeletal muscle. Unfortunately, it’s hard to study the heart in mice because mice do not have heart problems like there are in humans. These mice are missing the same gene, the same protein is gone, but then they still have a normal heart. Sometimes mice and humans aren’t the same and it’s hard to test that out. What I’m trying to figure out is if these miniature gene therapies are helpful in human cells. What I do is make stem cells from blood draws from the patient and then make those stem cells into heart cells. Then, I study more at a cellular level. It’s not a whole heart, though. “Does the cell behave more like a healthy cell if you give it this gene therapy? What is the most effective type of protein to deliver? Could the existing therapies be helpful to the heart?” Those are some questions I’m trying to answer right now. 

Are there any other animals with similar genes that these therapies could be used on? 

The other animal model that’s been used is dogs. It’s also still problematic because it takes a long time for heart problems to develop. In humans, it happens in their 20s, and in a dog, it might take a few years. It seems like the dogs also have differences depending on the breeders. Sometimes it’s hard to get consistent results. It’s called phenotype when you have a manifestation of a disease or a trait. The heart phenotype, where it’s degenerating, is inconsistent in the current animal models. 

How do you value success and what does success mean to you, especially with being so heavily involved in a career where success is taken more lightly?

For my immediate goals, I think about how success would be for me to be able to run my own lab at a research intensive university. I also really value passing on this process of doing science and being able to mentor the new scientists about how to do a well-controlled experiment and to be excited about the process of discovery. I try to have goals in terms of how I assess my success. Every day you can celebrate something. Earlier this week, I was trying to do a simple experiment and it kept failing. I realized what was wrong just yesterday. It was a small error where there are 2 places the reaction could have occurred. I did consider that second part of the reaction and then I was able to quickly troubleshoot through it. That gave me a small feeling of success. I was able to pinpoint where the error came from and make progress. You also have to celebrate your small wins.  

Are there any projects/research you’re currently working on that you feel will be groundbreaking in the future?

Our lab studies muscle in general. One large aspect of the focus of the Blau lab is to study how the skeletal muscle acts differently during aging. It’s been captivating to listen to and see the projects of my labmates who focus on regenerative medicine. They’re looking more at the skeletal muscle and how different strategies can delay aging.

What would you say to young girls who are interested in a job in STEM?

I would just say that you want to surround yourself with positive people who are encouraging and who help you get to your goals. It’s uplifting to be engaged in activities that you find motivating and whether that be hobbies or something related to your career trajectory. Something that gets you excited to wake up in the morning is really important. Another thing is to be kind to yourself because sometimes we put a lot of pressure on ourselves to achieve all of these things.

Image courtesy of Head Journalist Addison Evans with Dr. Asuka Eguchi

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