DULGUUN Amgalan, Ph.D. at Broad Institute of MIT and Harvard - On Leading Genetic Heart Disease Research
Interview and Photos by Nomko Baatar.
I’ll be honest, sometimes I think that written articles are slowly going out of vogue with readers. Today, our life stories and lessons are readily available and attainable through easily digestible media such as podcasts, video interviews, and even social media stories. So it’s an honor that this issue’s interviewee, Dulguun Amgalan, who herself has released several podcast episodes on “Time Out by MYLN” as one of the board members of the Mongolian Young Leaders Network (MYLN), agreed to sit down with me for an interview to discuss her recent accomplishments and future career.
We met the day before her paper, the fruit of her 6-year work, was published on Nature.com, the world’s most cited scientific journal with one of the highest impact factors. The title of her paper, co-authored with her Albert Einstein College of Medicine colleagues, is “A small-molecule allosteric inhibitor of BAX protects against doxorubicin-induced cardiomyopathy”. In non-scientific language, her team found an agent that can prevent heart failure caused by toxic chemotherapy drugs. This is a huge deal.
Her passion and achievements in the field of biology suggest a serious and scholarly demeanor, but those close to her know that she’s quite mischievous behind her playful smile. From her Hobby days until now, she has always been proactive in establishing meaningful relationships and seeking out communities that match her intellectual wit. However, with her recent move from New York to San Francisco via Boston, Dulguun indulged me in my request to spend the day with me meandering through New York, chatting and photographing her. The great thing about sitting down with someone for an interview for a prolonged amount of time is that you understand them indirectly through small tidbits and facts - and it’s clear that Dulguun is someone who cares deeply about solving problems. She doesn’t care for the accolades and recognition as much as about just getting things done. Through nibbling on (too many) scones in a tea shop, looking for Mongolian dinosaur bones in the American Natural History Museum, and enjoying a crisp winter day in Central Park, you understand that it’s very important for her to have younger generations to have someone to look up to in any given field and say, “Hey, I want to do that too”.
In this article, you can learn more about Dulguun’s past research work at the Albert Einstein College of Medicine in New York and University of Tokyo in Japan, the differences between heart attacks and heart failures, her new endeavor in genetics at Harvard, MIT, and Stanford, her interest in both listening to and making podcasts, and her love for ramen - to the point that we ended up getting ramen for dinner.
This interview has been edited and condensed.
Full name: Dulguun Amgalan
Hobby Alumni: 2005 (years attended 1995-2004)
Higher Education: B.Sc. in Biochemistry from University of Tokyo, Japan (2012); and Ph.D in Biomedical Science from Albert Einstein College of Medicine, USA (2018)
Sector(s): Biochemistry; Biomedicine; Genetics
Current Workplace: Broad Institute of MIT and Harvard
Past Workplaces: Albert Einstein College of Medicine
Languages: Mongolian, English, Japanese
Countries Lived In: Mongolia, Japan, Canada, USA
Current phone: iPhone 11
3 Apps to Recommend: Twitter, Overcast (podcast), AllTrails (hiking)
3 Books to Recommend: “Emperor of All Maladies: A Biography of Cancer” by Siddhartha Mulkherjee, “She Has Her Mother’s Laugh” by Carl Zimmer, and the Harry Potter series by J. K. Rowling
3 Movies to Recommend: Inglourious Basterds, Fargo, Okuribito
3 Songs You Are Listening To Most Right Now: Joe Hisaishi scores, Hans Zimmer scores, Holy Ghost by Bent Knee
3 Podcasts To Recommend: For current events - “The Daily” by New York Times, for foreign policy - “Rational Security” by Shane Harris of the Washington Post and Susan Hennessey, Tamara Cofman Wittes and Benjamin Wittes of the Brookings Institution, for biotechnology - “First Rounders” by Natural Biotechnology
3 Twitter Accounts To Recommend: Ed Yong @edyong209, Eric Topol @EricTopol, Neil deGrasse Tyson @neiltyson
ON CAREER
1) So you’re moving from New York to Boston soon. I would love to know what you’re going to be doing there!
I just took a position at the Broad Institute of MIT and Harvard, where I’ll be for the next few months before moving on to the Stanford Cardiovascular Institute in California. I'm changing my field to genetics as I'm looking toward the future - right now, we’re in the era of genomics. Before, sequencing the genome was very expensive, but the cost has dramatically decreased to the point that we can afford to sequence the hell out of everybody who comes in to get treated for cancer and other diseases.
“Because we are learning a lot about how our genetics play a role in diseases (we’re still in an exploratory stage), the next 10-20 years is truly going to be the era of genomics. ”
2) What are you going to be doing in your new role?
I’ll be doing both experimental and computational work - performing a lot of experiments with patient samples, manipulating the DNA, and analyzing the results. Specifically, these experiments will be done using the CRISPR technology, which is a simple yet powerful biological tool for editing a specific part of the gene, for example, for replacing an existing dysfunctional DNA with a new functional one. It’s something very cool and has already been proven to be popular with researchers in the field.
3) Was it a natural transition from what you were doing before or did you have to switch gears a little bit?
It was natural in a sense that I’m still studying the heart, but the approach is quite different. For the past 6 years, I've been focusing on common heart diseases, such as heart attack or heart failure, that mainly manifest in adults. These syndromes occur along your lifetime as a consequence of both genetic as well as environmental/behavioral factors, such as smoking and unhealthy diet. Our group has been trying to develop treatments based on knowledge accrued over the past several decades. But now I’ll be more focused on a condition called congenital heart disease. For children born with heart defects, genetic factors are being realized as an important component of pathology. Since we don't really know how that works, it’s going to be really exciting to discover what’s happening in their hearts. In that sense, it's going to be really different.
4) Please tell me more about your recently published paper and research.
At the beginning, we were trying to discover a drug that inhibits cell death that occurs during heart diseases. Your heart, which is the basic pumping unit of the body, is largely made of heart cells.
“The cells in your body have two decisions - to either live or die. The balance between these two decisions is what maintains your normal physiology.
If there’s an imbalance, such as too much cell survival, then that can lead to cancer. On the other hand, if there’s too much cell death, that can lead to heart diseases or strokes. ”
We were interested in the latter. Why do heart cells die excessively and what kind of drug can prevent that from happening?
Furthermore, there are many different types of heart diseases, so we focused on heart diseases caused by cancer chemotherapy. When cancer patients undergo chemotherapy, the toxicity of the anti-cancer drugs affects not only the cancer cells, but also the cells in other organs as well. As most people know, loss of hair and kidney damage are some of the more prevalent types of unintended consequences. However, heart cell death is another unintended consequence for certain groups of cancer patients: older adults, children with hard-to-treat cancers, patients with recurring cancer, and those who have received other cardiotoxic treatments, such as radiation therapy.
“Since we’re dependent on our hearts for survival, it’s important to block chemotherapy toxicity from affecting the heart. The BAI1 drug we developed prevents such excessive heart cell death. ”
5) How does it work?
Interestingly, cells have their own machinery to commit suicide. If cells are in a great environment, they want to continue living and dividing. But if they’re not, then they get a signal to turn on a genetic program that kills them. There are certain instances where cell death happens naturally, such as during embryonic development, when cells cleanly commit suicide and disappear. However, this also happens in disease contexts where the consequences are not beneficial.
“We exploited the fact that cell death is a very controlled genetic process and we know how to interfere with it. That’s why we studied cell death during both normal and disease contexts to understand the underlying processes behind it. ”
6) What were the differences between normal and disease environments?
We took advantage of a protein called BAX, which is a master regulator of cell death. In its normal state, the BAX protein is inactive inside the cell, but once it receives a signal about a toxic environment (e.g. heart attacks), then the BAX molecule changes its shape to become very lethal, affecting the mitochondria and signaling the cells to die. This is also known as a point-of-no-return event because once BAX commits the cell to die, there is no coming back.
7) So are you turning the BAX molecule off, then? What exactly does the drug you found do?
Well, the issue arises only when the BAX changes its shape, so the BAI1 drug attaches itself to BAX and prevents it from changing shape. This prevents the toxic chemotherapy drugs from damaging the heart without lessening its anti-cancer properties.
8) Wow. How did you come upon developing the BAI1 drug?
It was an extremely collaborative process from start to finish. BAI1 was one of many chemical compounds created by a pharmaceutical company nearly two decades ago, but the very first insight that this drug could be binding to the BAX protein was made by one of our senior lead scientists, Evripidis Gavathiotis, who had previously solved the structural rearrangement of BAX. From there, we worked hard to find the exact mechanisms of the BAI1-BAX interaction and its potential medical applications. Usually, academics try to understand the underlying biological processes behind an observed occurrence while drug companies use that information to develop the drugs (although drug companies do have research arms). It's an organic collaborative process - you need to know the biology to find drugs for certain diseases, but you also need to use the industry technology in academic biological research. The BAI1 drug was one of the many versions we tested.
9) What were some of the challenges you encountered during your research?
A lot of things don't work. I think probably 95% of your experiments fail, but you need to have a really strong will and perseverance to push through and continue generating reproducible data that supports your hypothesis. Or your hypothesis could be wrong and that's fine, but you have to be prepared for that possibility. Maintaining that kind of mentality is very difficult.
10) What were your main coping mechanisms to handle that stress?
At the end of the day, you have to enjoy what you’re doing even if the results are not what you expected. The process of designing and performing the experiments and analyzing the data itself is really fun.
“It’s really cool to discover something just by yourself, something that you thought of, and something that nobody else knows - that kind of feeling stays with you.”
You can't go down the rabbit hole of trying to prove something that’s not true because the data is the data. If you find something and it doesn't agree with your hypothesis, then you modify it and evolve.
11) What was the most rewarding thing you’ve gotten from this journey?
Discovery! (laughs). That feeling is something that people can’t let go of, and it’s the reason why academics stay in the sciences. From chaos you’re finding something great.
12) Who were your biggest inspirations and mentors?
I’m really inspired by my PhD advisor Richard Kitsis, who’s a Professor of Medicine and Cell Biology and Director of the Wilf Family Cardiovascular Research Institute at Einstein. He's a very generous person - when his students need him, his door is always open because he wants to help the next generation.
“I feel like it’s really important in every field that you look out for the younger generations and help them advance because everybody goes through the same thing at some point.
What I learned from Richard Kitsis is to give back to the community and just be helpful, which I have tried by mentoring a few students. ”
13) How did you choose him? Were you assigned to him when you first started as a graduate student, or did you find him yourself?
In the US, you get to rotate through different labs before choosing a specific professor to work with directly. I chose my advisor’s lab because I was really interested in his research on cell death. He is one of the founders of the cardiac cell death field and discovered important molecular processes that occur when a heart cell dies during heart diseases.
14) Did he influence your thesis topic? What were some of the other things you had to take into consideration?
Usually, when you start off as a graduate student, you have a conversation with your mentor on the exact research topic you want to pursue. Your advisor will have several ideas and ask whether you'd like to study them. Or if you have a research topic of your own, then you can convince your advisor that it’s a feasible topic to pursue.
15) How do you work with your own students?
I supervised a number of students over the past few years who wanted to do hands-on research before deep diving into medical school or PhD programs. It takes away from your time, but you also learn how to communicate and help people advance in their own pathways.
16) What are the biggest things that you took away from your mentor that you apply yourself when you are teaching others?
I learned to be patient. When somebody is just starting out, it's really hard and everything is very confusing at first, so you just have to be really patient with people.
17) What were some of your most humane moments in this journey?
One of my students wrote about her work at our lab in her college applications. She later emailed me saying that she got into her dream school, so I was happy that I helped her at least a bit in achieving her dreams. All of my students keep in touch with me, and I am hoping to see them again soon.
18) Would you ever consider moving into a more community related field?
I think when you advance in your career, you naturally have to work with people. We collaborate with a lot of folk - if you look at my paper, you'll see that there are other co-authors besides me. We get advice from many other scientists and institutions. I wasn't really sure what to expect from entering this field, but I have realized more and more that it's very interdisciplinary and collaborative. You can't do science by yourself.
19) How is it like working with a team of scientists on such a project? How did you find them?
We approached experts in their fields internally at Einstein as well as at other universities. For example, it’s really expensive to test on mice, so we approached the zebrafish experts at Harvard Medical School because testing drugs on zebrafish is quicker and cheaper than on others. In that vein, when you approach specialists and discuss your project, they usually get really excited about being involved and agree to collaborate.
20) Having worked both in Japanese and American labs, what are the main differences you’ve observed?
“Culturally, everyone in Japan is a workaholic, especially in academia, so it was hard to adjust to that at first. I had to start at 9-10am and stay until 12-1am in the lab, which was normal. Not that people in America don’t work hard, but I think there is a better work-life balance here. ”
Something else I’ve noticed is that in American labs, you work heavily with your mentor on writing grants for funding. These grants can be very generous once you get them, but also highly competitive and well-regulated in terms of requirements during the application process. The grant writing period is a very stressful one, but I learned a lot about how to present my research to the government and the public. But in Japan, there isn’t much opportunity to get involved in the grant writing process as a student.
21) I’ve read that it’s extremely hard to get national grants, and that sometimes US science students and labs have to rely on private or corporate funding, which may limit the freedom you have over your research. Have you seen that to be true?
Getting national grants is extremely competitive, which is why students have to rely on other sources of funding. I actually got a grant from the American Heart Association, which is a non-governmental private entity. They placed no restrictions on me as long as I was working on impactful research that could lead to the cure for heart disease.
“Overall, I think there are a lot of opportunities for grad students in the US to get foundational, governmental, or nonprofit funding.”
Also, while you don't need to have funding to get into a PhD program, your lab and professors need to have grants to fund you initially. That’s one of the factors you need to consider when looking for potential mentors.
22) What are some of the other things that you wish you knew before starting your PhD program? Anything you would want to share with anyone considering entering this path?
I didn't really realize how long it could take (laughs). I thought I could do it in four years, but that wasn't the case. Depending on the project, sometimes things are out of your control and you have to be patient. But even if I knew that, I would have gotten into it anyway. However, if you’re on the fence, then you have to know that there will be a lot of setbacks during graduate school, so talk to other people and learn about their research and experiences. That’s why it’s also really important to choose your mentor well because they make a huge difference in whether you will enjoy graduate school or not.
Another thing I didn't realize, which turned out to be a good thing, is that…
“...there are so many career paths for PhDs. You’re not only considering an extended career in academia, but also other career paths in consulting, biotech companies, pharmaceutical companies, science writing, and so forth. ”
Coming to the US helped me realize that I don't have to restrict myself to one career, whereas I think I would have taken the more traditional pathway had I stayed in Japan. I’ve realized here that sometimes opportunities come out of nowhere, and you just take them and go with it.
23) So what did the process look like when you were applying for post-graduate positions?
In academia, it's really just cold emailing (laughs). While economics or medical students might have more organized processes, there's really no structure to how we advance from PhDs to the next level in my field. So if you’re interested in a certain lab and their research, you email the lab head about your interest and their open positions. In my case, I contacted a group leader at the Broad Institute and we both realized we could be a good fit. He then called my references, who gave good recommendations, and invited me for an on-site interview to meet the lab members and present my PhD work to them.
24) I don’t think I’ve asked you this yet, but what made you choose to pursue a PhD?
I never intended to become a PhD, but in my 4th year of college at the University of Tokyo, I was doing very interesting work on circadian rhythms and how that affects memories. The project was also focused on proteins, and I wanted to continue my research on them.
25) What did you find out about the circadian rhythms?
There’s a dynamic protein in your brain that shuts down during the day and resurges when you’re asleep, while most proteins are not like that. When you knock out this gene (“deleted the gene” in non-scientist language) from mice, the animals have a lower capacity to memorize objects, which means that this protein is important for memory formation. My research on trying to understand this protein was the very first research I’ve conducted in a lab - unless you count the chemistry lab at Hobby, which is not really research. I mean it’s fun, but it’s not real research (laughs).
AT HOBBY SCHOOL
26) Were you into biology even back at Hobby School? What were your favorite subjects there?
My grandma was a high school chemistry teacher, so I was really inspired by her. At Hobby, I was interested in physics and chemistry - they were very logical to me. But I started to focus more on biology because the International Baccalaureate (IB) program at the International School of Ulaanbaatar (ISU) had a really great biology program.
One of the biggest things I can attribute to Hobby School is definitely learning English. When I entered the 1st grade, some of my classmates who went to the Hobby preschool had some level of English already, while I didn't have anything. But I caught up with them almost within a month.
27) Oh, you went to ISU for your last 2 years of high school? I didn’t know that!
Yes, I did. Oh no, am I ineligible to be interviewed now? (laughs) I guess in my heart, I always thought of myself as more of a Hobby girl more than an ISU one. I attended Hobby from 1st to 9th grades, and then attended and graduated from ISU on a scholarship for the last 2 years. ISU offered the IB program which was recognized in US colleges, and I took three high level courses in Biology, Chemistry, and Math, and three other courses in History, English, and Spanish.
28) Hahah, do you know there’s a popular meme now that the only thing students remember from high school biology is that the mitochondria is the powerhouse of the cell?
That’s true!! Mitochondria IS the powerhouse of the cell, and you can find it from any textbook. Well, the funny thing is, I study mitochondria now.
29) Do you speak Spanish now?
No hablo español (laughs).
30) Any other languages?
In desperate life and death situations, I should be able to recall Spanish and Russian (laughs). Japanese, of course, but I’m afraid of losing my fluency as I keep living in the US. My new resolution for the new decade is to become fluent in Portuguese at the level of a ten year old (laughs).
31) I remember that one time when we were talking to some other Hobby alumni about our Hobby memories. You said you were very mischievous at Hobby. What were you usually up to at Hobby?
Haha, I was! I always used to fool around. When teachers lectured in classes, I would imitate them in a loud voice and the entire class would burst out laughing.
“We had quite a community at Hobby, and I have only good memories of it now. Of course, when you spend so much of your childhood in one class, you can only be fond of it. ”
32) But coming back to school, you mentioned you were interested in studying in the US. What led you to study in Japan instead?
Well, I had an open mind to everything. While I did consider going to the US, I also wanted to go to Japan because I’ve been there as a kid and I knew the language already. Additionally, one of the primary things I was looking for were scholarship opportunities, and at the time, it was very hard to navigate the US college application system.
“Can you imagine, the Common Application was by paper, so you had to mail your applications in? You wouldn’t even know if some of your applications reached their destinations or not! ”
My family didn't know anything, both ISU and Hobby were very new so there was no alumni network established, and because the teachers could do only so much, I had to do everything by myself. On the other hand, the Monbukagakusho Scholarship (also known as the Monbusho Scholarship) offered by the Japanese government was very systematic and easy to follow.
33) Tell me more about the Monbusho program.
“The Monbusho scholarship program provides a full scholarship plus a stipend for 5 years in Japan, with no strings attached. At the time, they didn’t accept a lot of students in their natural sciences program, so I was one of only two students in my program.”
I remember right before the interview, the candidates were all sitting in one room, and one of them turned to me and asked me what I was pursuing. When I answered, he retorted, “Oh, you're probably not going to get it. They only take at most 1 student in a year in the sciences”. While I was dispirited, I still wanted to try my best since I came that far anyway, and faced the conflict head on. Even now, my mentality is that I can't change a course that is already in motion, and I can’t continue thinking about what happened in the past, so I just try to focus on the moment.
PERSONAL
34) And right at this moment, I know we’re in New York, but if you were in Japan right now, what would be the first thing you do?
I would go to a ramen place. And then I would go to an okonomiyaki place. Hovdog shd (laughs). However, the food portions in Japan are tiny. My male Mongolian friends were rarely satisfied.
35) What were some other Japanese social norms that took you aback?
Everything is very etiquette based - you have to talk in a certain way to certain people, so it’s kind of like learning 2 different languages.
“I used to be the president of the Mongolian Student Association in Japan (Yamokh), and we worked with a number of Japanese people who supported our organization. To communicate with them, we had to be super formal, schedule everything in advance, and be very structured in general. People are very shy in Japan; however, once they drink, they do open up a bit. ”
36) What did you do for fun in Tokyo?
We used to karaoke a lot. I’ve also traveled extensively to Hokkaido, Sapporo, Okinawa, and Hiroshima, which was a bit spooky (laughs).
37) What was the advantage of pursuing your graduate degree in the US as opposed to staying and pursuing it in Japan?
In Japan, there's no point in staying for a graduate degree unless you’re in a niche field. Otherwise, the funding is limited, especially when it comes to experimental set ups. If I stayed, I would’ve been continuing my research on circadian rhythms, but I decided to come here instead to concentrate on new research. Additionally, in my field, the US specifically had much more impressive resources and labs, and many papers I was reading were published in the US.
“While at the University of Tokyo, I took a summer internship in the US, where my boss was a graduate of Einstein. He actually introduced me to my school, which, in turn, wooed me into attending their program. ”
38) Did you expect yourself to have moved to New York? And was the first thing you did here?
I didn't think I would've moved to New York, but it happened that way. It was an easy transition, but the only hard part was getting used to the chaos of New York - Tokyo is so clean, everything is on time, and the subway system is really good. I moved here in 2012, went window-shopping on Fifth Avenue, and later went up the Empire State building. At the time, I didn't know a lot of Mongolians here, but slowly, after a while, the Mongolians in Japan started coming to New York.
39) Oh right, I first met you through a mutual friend who studied with you at the University of Tokyo and later with me at New York University.
Remember, we first met when we made buuz at his place, and the jignuur was so small that everyone just had 1 buuz on their plates (laughs).
40) We also made duguin huushuur another time! What else do you do to relax?
I play racquetball - it’s a good way to let out my stress. I was also part of the Bronx Irish Women’s Soccer League - my colleagues from Einstein recruited me into it. Apparently, Irish people establish soccer leagues wherever they settle down. But in general, I do like team-based sports a lot.
41) I do think the kind of sport you play says a lot about you as a person. People who like individual sports such as running tend to be more comfortable by themselves, while people who like team-based sports tend to be outgoing and communicative. And speaking of which, I know you’re very involved in different communities, such as the Mongolian Young Leaders Network. How’s that going?
I’ve been interviewing some of our members for our podcast - I did three episodes so far. I’m learning a lot about interviewing, editing the sounds, and putting together the final product. I’ve been really into podcasts lately, so being on the other side working on them is interesting too. Recently, I’ve been listening to this podcast called “Best Known Method”. In one episode, a professor at Harvard Medical School discusses the genetic causes of heart attacks. It’s fascinating to hear him tell his story about his discoveries and thought processes, and what leads to new insights. I would say his approach is different from mine, which is why it’s enjoyable.
42) Ok, if we lived in a perfect world, what would you be doing in 5-10 years?
I would like to continue my research back in Mongolia, but that would require a lot of funding. Otherwise…
“I’m looking forward to collaborating with the biologists, chemists, and engineers at Stanford on interdisciplinary innovative research to discover new ideas and technologies.”
43) What do you think is the most relevant research needed in Mongolia today?
From my perspective, it’s more biomedical research. It’s expensive, but there are a lot of health problems that need to be addressed. Also there are opportunities to discover interesting biology that is unique to Mongolia.
44) Anything else you want to share with current Hobby students?
“Keep learning and don’t take shortcuts. At the end of the day, our teachers say very cliche things like, “No one can steal what’s in your mind”, but that’s really true. It stays with you - you have to live it to learn it. ”
45) Who would you recommend to interview next from Hobby Alumni? And why?
I want to recommend Tenuun Batzorig, my dear friend and fellow classmate, who is an architect working in a Washington D.C firm. I think her story of coming to the U.S. right after Hobby, studying and working immensely hard to achieve her dream job will be an inspiration to many. But also she is just a cool person who is interested in the arts, music, and many other things, so it would be interesting.
“From my perspective, the most relevant research needed in Mongolia today is more biomedical research. It’s expensive, but there are a lot of health problems that need to be addressed. Also, there are opportunities to discover interesting biology that is unique to Mongolia. ”