Young Jin Kim is a GS5/MSTP doctoral candidate in the Adrian Krainer Lab at Cold Spring Harbor Laboratory. Young Jin studies how synthetic antisense oligonucleotides (ASOs) can be designed to change post-transcriptional gene regulation. His dissertation work shows that ASOs may help treat hereditary diseases where harmful mutations cause defective splicing or degradation of messenger RNAs. Young Jin explores the therapeutic potential of ASOs in cystic fibrosis as well as the rare disease familial dysautonomia, which affects the development of the autonomic nervous system.
Young Jin sat down with us in October to chat about finding his way into genetics research by following his interests and staying motivated by keeping company with excellent scientists. He also discussed what studying rare diseases has taught him about the importance of science communication as well as his strategies for building resilience while on the research grind.
Name: Young Jin Kim
Hometown: Seoul, Korea
Dissertation Lab: Adrian Krainer Lab, Genetics Program
Clinical Interests: Pathology, medical genetics, or neurology with a focus on the neurodevelopmental disorders. “Anything that lets me focus on molecular biology and genetics.”
Tips for resilience: Find cheerleaders, avoid getting jaded, learn a good chokehold.
What were your early lab experiences like? Were you always looking at RNA?
No, initially, when I was an undergrad at SUNY Binghamton, I was in a lab that studied ion channels. Actually it’s kind of a full circle [to be working on ion channels again in cystic fibrosis]. My PI, Dr. Christof Grewer, studied the biophysics of sodium ion channels and peptide transporters. But my early research experiences were pretty depressing, I think, because they didn’t work out very well.
During summers, I studied how mutations in nuclear lamin genes cause muscular dystrophy in Dr. Howard Worman’s lab at Columbia University Medical Center. There, I had a mix of success and failures. Fortunately, I published a second-author paper based on this experience.
How did you decide to pursue the MD/PhD despite discouraging results early on?
I came to Stony Brook as a regular MD candidate, but I ended up making a lot of friends in the MD/PhD program like Ping [He], Nick Schwartz and Alex Jares (MSTP MS4s). I was in anatomy group with Ping, Nick and Alex, so we had a lot of interactions and being around MD/PhDs helps you maintain a certain mindset.
Then the summer after first year, I did an internship at an HHMI lab in Duke. I worked in the Van Bennett Lab, studying ankyrin, an ancient family of membrane-adaptor proteins that’s important for all sorts of things [and are implicated in channelopathies].
After second year, I took a year off of medical school to do the HHMI Medical Research Fellows Program. I worked in Dr. Iva Greenwald’s lab at Columbia University that studies C.elegans genetics. This was a really important experience because I got to interact with a lot of different scientists who were doing super cool things. And the project that I did there—I did everything I could do: tons of cloning, a lot of hours in the microscopy room—but, again, the project didn’t pan out very well.
But [despite not getting good results,] it was fun to interact with scientists, and I found the process of research interesting, so I kept at it.
After that exposure, when I told my wife (who was my girlfriend at the time) that I wanted to do the MD/PhD, she was like, “What! What are you talking about!”
Haha!
No, she was actually very encouraging!
In the Krainer Lab, you’re working on interventions for cystic fibrosis and familial dysautonomia, but at a genetic, transcript-level approach. It seems like you could take expertise in many different directions clinically speaking, toward many different congenital conditions. How does your dissertation work bear on your clinical interests?
Recently I went to a small consortium hosted by the Familial Dysautonomia Foundation, and there I got to meet some physician scientists who do clinical trials also. I had never really put a lot of thought into doing clinical studies, but doing the actual science with the data coming from patient – I think that’s very interesting also.
For a long time now, I have found the RNA and molecular biology underlying different diseases more interesting [than their clinical aspects], so I never had a particular specialty in mind. If the underlying biology is interesting, that’s where I would like to go.
Could you expand a little more on some of attraction and advantages—or challenges—you perceive in doing clinical research?
If you want to be a physician scientist who does translational work [in the clinic], I think you need some level of skill in scicomm or science communication, so that when you try to convince patients to engage in your clinical trial, you can convince them that it’s important. If you can’t communicate how the drug works, let’s say, and the benefits or risks that are associated with it, how the drug can ultimately benefit the patients and the disease community overall…. It’s really going to be hard for the patients to engage.
The Familial Dysautonomia Foundation is a great example…. There is a very small patient community and because of that, the participation of every one of them is crucial. Regardless of the size of the patient population, if you want to bring people to a translational study, you need to be able to engage the patients. But the importance of scientific communication is so immense for familial dysautonomia. One of the big things that the Foundation and the scientific community around familial dysautonomia think about all the time is how are they going to get the message out to the public and how are they going to encourage participation [in clinical studies].
And even in the case of Spinraza, [an FDA-approved ASO for spinal muscular atrophy], there’s been a lot of effort by the SMA Foundation improve awareness about the disease, and this had a tremendous impact on, say, getting the drug covered by insurance companies. So if we’re just talking about the very basic molecular biology, you don’t have to communicate all of that to the public, but if you’re going to move something forward in the clinic, you’re going to need that skill set.
Earlier in the interview, you mentioned a couple times where your research “didn’t pan out well.” What were some ways you overcame the discouragement of projects not panning out as expected?
I think I learned not to take myself too seriously.
What was a time you took yourself too seriously?
You know, like… when your experiment doesn’t work – but that was almost every day for the first year and a half!
What was it like for the first year and a half?
Awful. I was trying to identify ASOs that can do what I wanted them to do, and I just couldn’t do it. Some days you even know this experiment is not going to work, and you look at your data, and you’re like, “Yay, it didn’t work!” Like I was fortunetelling, almost.
But I think in those moments, when you haven’t been punched in the face by the data that many times yet, I think you need some people around you to help you to keep going and stand up. It’s really hard to nurture that [resilience] by yourself when you’re so young. You need people who will be like a personal trainer to encourage you from the side, telling you, “Yeah! You can do it!”
Who were some of your “personal trainers”?
My wife. She is unconditionally saying, “Oh yeah, it’s fine, you’re doing a great job.” I mean, sometimes, she might say it just because she needs to say it, right? But even those kinds of encouragement all help.
In the beginning, you need some nurturing from people. It’s always better to hear it from a senior person whose opinions you care about. It’s good to have some nurturing communication. From there, you start to grow thicker skin, and you can deal with failure a little bit better.
Did your PI or other folks in your lab play that role for you?
My PI is a nice person. He is encouraging, but he’s not the cheerleader type. He’ll say things more like, “Believe in it, and keep working on it.” He doesn’t put you down for experiments that didn’t work, but he doesn’t like to hype up things. He’s a very honest person. So he’s not going to promise that it’s going to work no matter what. He gives a very real analysis of what’s likely. He’s a firm foundation where you can feel that, “if I just continue it will be okay.”
But that’s not always enough to get you out of bed the next day [after a failed experiment] and into lab. Friends like Tomoki Nomaguchi [MSTP graduating class of 2018] were helpful. He was very encouraging.
Especially in the beginning it’s important to quickly identify people you can trust, and I think it’s completely fair for you to expect some nurturing from them. And then you later pay back.
How have you paid back?
I try to be as encouraging as possible without just saying things. Stony Brook MSTP students are very smart, so I don’t have to try to prove that they’re good students. I just need to remind them that they’re good. It can be really hard to remind yourself that when you’re busy beating yourself up and taking yourself so seriously—I mean, 90% of our experiments fail, so we deal with it every day… including me. But then someone – either you or someone else – is going to have to help you stay encouraged and stay healthy.
When you say “you or someone else” needs to help you stay healthy and resilient, apart from finding a good support base, what are some other ways you’ve helped yourself? Are there certain good habits you’ve maintained?
I picked up a new hobby in medical school. That was Brazilian jujitsu.
Did you do martial arts before?
I started Taekwondo when I was four… maybe three. And I kept doing that. And then I did like Aikido for some time….
Do you just have multiple black belts in different martial arts?
… Kind of.
So modest! All right, then! For someone who had already mastered Taekwondo, why switch to Brazilian Jujitsu? What was different about it?
The initial interest was just, “Oh, it’s cool.” [I knew of it as] the foundation of all mixed martial arts, but I’d never tried it. Then one day, I just decided to try it in first year of medical school. I’d started by the time we were leaning about the brachial plexus [in anatomy] — I remember that because I’d gotten a little injury from jujitsu, and I could kind of trace the nerves along the limb and stuff like that…
What’s super different about jujitsu is that it simulates aggressive scenarios as realistically as it gets in a controlled setting. That sort of scenario where someone’s actually trying to hurt you is really hard to simulate in a lot of [other] sports martial arts. But in jujitsu, either someone’s actively trying to take a limb or they’re trying to choke you out. Because that’s the way a match ends; there’s match time, but it can also go on and on until someone—
Have you ever taken a limb??
I never… I mean, yes, of course? But the limb is still on the person! It’s just an expression‼
So we’re trying to do joint locks or chokes—that’s how a submission occurs. But in addition to that, the physical interaction is very aggressive. Initially, I was not able to manage that type of situation. You get an adrenaline rush because your fight or flight engages right away, and when you do that, you tire out super fast. And so my first day, I got choked out and arm barred by a girl who was like five feet tall—much smaller than me—and I was throwing up by the end of the class. I was like, “Ugh, this is horrible. Sign me up.”
What came out of that was I learned to manage any kind of stressful situation in research. You learn how to manage stress a little bit better.
So do you ever choke out your laptop or—
No. But also when I get really upset, I can release that aggression in a controlled manner, with a trained partner where there’s mutual trust. So I think that was good. Anything that helps you to release your stress is good.
And for these kinds of activities, it’s a form of dynamic meditation. You’re actively moving but you’re so focused in that particular moment that it’s almost like meditating. You forget about the stuff that didn’t work in the lab, and you can just focus on the moment, and you feel much better.
If you can find anything like that, you should do it; it doesn’t have to be jujitsu.
Is there anything else you’d like to tell the MSTP community – general warnings or advice or if you have some sort of personal motto?
At the PhD stage, the most important thing is to not be so jaded and find whichever way you can to not be jaded. It’s essentially a learning experience, right?
I want to be clear that I don’t mean we have complete control over whether we want to be jaded or not. The environment can drain us of enthusiasm and make us tired. I want to express that we have to monitor ourselves, and find ways to get out of it if we do [get jaded].
What does it look like to be jaded?
You start thinking everything is bullshit, and you lose interest in everything. Maybe your drive to learn gets lower and lower. You see a lot of smart people as you’re doing the MD-PhD, and I think that’s another factor that may make you more jaded—like, “What am I doing? That person is publishing in [Cell, Nature, Science] journals, and I’m still working on whatever.” But their project is not your project. The question you’re pursuing is different from any other. And after some years in your research, you’re probably the only one who can do what you do – or maybe a very small handful of people who know how to do what you do. You need to remind yourself that and continue to learn to do things.