Dr. Henry Lee

What do you do on a daily basis for your job? What are the skills that you utilize? 

“I work at the Translational Neuroscience Center at Boston Children's, studying and developing translational therapy for diseases in a hospital setting. Our work is closely related to therapy and developing therapy for patients. We study bench work, typically using mice as a model to understand the biology of the diseases that we're interested in. We also test different drugs, and small molecules. Using the mice as a model, we can understand what the underlying biology is and then develop corresponding therapy to test on mice before we go into the clinic with these methods. That's what we call translational, because we are translating our knowledge from the lab to the clinic. It’s what we call the bench bedside translation.  

Over these years, my skill set has been molecular biology and biochemistry. I later expanded them in moving to working with mouse genetics models, using genetic manipulation of the mouse (because we know very well the mouse genome, so we can manipulate their genome and then to understand diseases that are relevant for genetic disorders).”

When did you first get interested in this career/career path? What steps did you take to get to where you are today? 

“I studied at a university in Hong Kong, and my main subject was biochemistry. So, I got a bachelor's degree in biochemistry, and when I started my thesis project in my last year of undergraduate program, I needed to do a laboratory thesis. I found a lab that was working on neuroscience, because I was interested in neuroscience, and started working in the lab doing research. After I finished my undergraduate studies, I got a master's degree at the neighboring laboratory in the same university. I later got a PhD at the University of Pennsylvania studying, again, neuroscience.  

My path was very direct because I started from biochemistry and then molecular biology as my background. In my PhD, I also used those techniques and work. What I'm doing now is more translational, so that means I'm moving that knowledge from the bench to the bedside. That's the new component that I'm now doing, especially in the hospital setting.”

Why are mice a good fit for your research? 

“Mice are a very good animal model for several reasons. One is because they breed very quickly, so we can quickly get a lot of mice. We use them to test different injuries, or different genetic manipulations in the mice. Another reason is because we already have the genome of the mouse fully sequenced, so we know precisely where the genes of the mouse genomes are. When it comes to studying genetic disorders which we are interested in at Boston Children’s, it’s very straightforward; you can directly target those genes on the mice and then manipulate them in certain ways to see if we can mimic the patient’s situation. Because the mouse also has a head and a brain, it also mimics some of the physiology in humans.”

What are projects you’ve worked on? 

“In my previous work, I studied a little bit of the autism behavior in mice. The mice are social animals, they live in a social setting, they live in a group, and they communicate. They talk to each other, although we don't understand their language, and they also exhibit certain behaviors. For example, they can have some autistic-like behavior, or they can have some communication problems. One example is hyperactivity, which is a behavior that we can study in the lab.  

The project that I am specifically studying is regarding a genetic disorder. It's actually an ultra-rare disorder, meaning only a few 100 people in the whole world have the disease. It's very interesting for me because of many reasons. One is because it fits very well with my background of biochemistry and biology, and my PhD, where I studied the brain and how it functions, particularly the inhibition of the brain.  

Essentially, the brain functions by two forces: one is excitation, the other is exhibition. The two forces have to be balanced. If there is an imbalance, it is what we call the “EI imbalance,” where the disease might happen. We also know precisely what gene it is that's having the problem. So my main project in the lab right now is to study how this gene impacts brain development.  

One way to think about gene replacement therapy is by putting the gene back into the brain to see if the replacement works. We show that the mouse without the gene continues having a phenotype (the symptoms) that is similar to the patients. However, once we put back the gene, we show that the mouse can actually recover, or what we call the rescue. This gives us a very good indication that gene therapy might be helpful for the patients.”

What is a challenge others may face when pursuing a career similar to yours? 

“A challenge that might be more relevant for the stage of high school could be identifying what your interest is. In my case it was quite straightforward; somehow, I identified my interest very early on, and I knew that this was something I wanted to do. I did see a lot of my classmates not having any clues as to what they wanted to do, and they wanted to try out different things here and there.  

If you want to identify what your interest is, identify what your passion is, and what you're confident in doing. And you don't need to be finding it out early on, but you should test out different things you might be interested in. Find a way that you can maybe read a book about specific subjects, or if it involves a lot of research, you might want to have hands-on experience and to be in the environment. For research particularly, it's a very engaging activity that you might spend a lot of time thinking about. So is that the lifestyle that you enjoy? Some people love that, some people want more of a work life balance.”

What is your advice on overcoming challenges? 

“If you want to overcome challenges, you should talk to many different people. Talk to people who might have experience, meaning they have done something similar before. Reach out to people who have experience and learn directly from them. Identify someone who can be a mentor. That would be very helpful no matter what stage of your career or your education. Find someone who has walked the path that you might want to walk and learn from them to see how they did what you want to do.”

Editor: Jieling Pua