Taken from ASBMB’s monthly research newsletter: The Monthly Digest (Feb. 2021, Issue 2). Written by Sahithi Gangaram

Liz Enyenihi is a recent Emory University College of Arts and Science Graduate. She is currently on a gap year pursuing an MD/PhD. Writer Sahithi Gangaram sat down to talk about her current research experience and journey.

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Q: When did you first become interested in science? What or who inspired you?

A: It’s hard to pinpoint one specific memory. I feel like I’ve always been the sort of person who has always asked questions about the world. I feel like I have always enjoyed it.

Q: How is science different now, during the pandemic, for you than it was a year ago? 

A: I think the most difficult thing is social distancing because I think a lot of great science comes from people talking to each other, and off-hand interactions where you can collaborate with other members of the lab. So, not being able to do that is kind of difficult. It can also be difficult for trouble-shooting. When you are having technical difficulties in the lab, usually like when everyone is talking it is easier to get to the bottom of the problem. But with people being far apart, it definitely makes it harder. And I think that, due to the pandemic, a lot of people have been able to do more dry-lab stuff and computational work, which has been different. I was actually able to start in-person research when I came to Yale SOM as a postgraduate research associate. When I came here in July, Connecticut was a bit ahead of some other states as far as a pandemic response– so they were able to have people in person. Our lab does split shifts, so the lab is always at fifty percent capacity. Half the people come in in the morning, half come at night. So I’ve been in-person.      

Q: What have been some of the biggest research challenges that you have faced? What did you do to try to overcome them?

A: I think for me something that has been the most frustrating is dealing with technical difficulties that kind of get in the way of getting to the science and really getting into mechanisms and understanding the problems you are trying to face. But, then, if you are dealing with technical problems like this machine is not working or antibody is not working or your buffer is not right– things like that. That can be kind of frustrating. I would say that that is challenging. And, also, things take longer, I feel like than you expect. So, sometimes, you get really excited and make a bunch of plans of what I want to do– like, okay, I’ll finish this in this amount of time, and next week I will do that. But then the first thing does not work, so you’re kind of back to square one. It’s all part of the process. I think patience is important to try to overcome those challenges. And, trying to get advice from others. You have to be humble and acknowledge the errors you might have done and things that you might not be seeing. I think it is really helpful to have other people that you can ask for advice, who are more experienced. That’s been helpful for me. So it is nice to be in a lab where people are supportive of each other.   

Q: Could you elaborate more on the research you had done in the Corbett lab in the Biology department of Emory College, modeling diseases linked to mutations in the RNA exosome using budding yeast? 

I was on a project investigating the RNA exosome, which is a 10 subunit protein complex that processes and degrades RNA. It both trims certain RNAs, like rRNA from the precursors to the mature form, but it can completely degrade other transcripts and it is not really understood how that specificity is regulated. And, additionally, mutations in different subunits of the exosome that are very similar in structure and function lead to very distinct diseases. So, my project was looking at mutations in one of the cap subunits. Previous work saw that mutations in a different cap subunit led to a neurodegenerative disorder, and then I was looking at a disease that causes symptoms such as short stature, hearing loss, vision problems, and symptoms that were overall very different from this first disorder — even though the mutations were very similar in similar subunits. So, because the exosome is very highly evolutionary conserved — from humans all the way down to yeast — we used yeast as the model system to try to investigate how these mutations are actually affecting exosome function. So, I did an experiment on how it is affecting the growth of the yeast, different RNA levels, and protein levels. 

Q: What led you to work at Yale’s School of Medicine as a Postgraduate researcher for the Department of Pharmacology?

A: I did the Amgen Summer Scholars program here over, and I really liked the program so I decided to come back. 

Q: What kind of research are you currently conducting?

A: I am in the pharmacology department, so I’m focused on drug-discovery research. My lab found that a chemotherapy drug could be repurposed to reverse signs of hypertrophic cardiomyopathy in the developmental disorder Newman Syndrome, which is one of the most prominent autosomal dominant genetic disorders. So, building on that finding, they found a key signaling protein– PCR transmembrane protein– that’s involved in the development of hypertrophic cardiomyopathy. But now we’re trying to find out what kind of signaling events are downstream of PCR. So that’s what my project is currently looking at. So first we used RNA seq as an unbiased approach to finding potential targets that were upregulated in the disease, but then came back down with the mutated PCR transmembrane protein.  

Q: What are some of the aspects of your research work that you really like?

A: I think its just exciting to know that you are finding something that no one has ever seen before. And I think it’s cool when different things connect in ways you weren’t expecting. So for example, in my project right now, we’re essentially focused on heart symptoms. And one of the novel targets identified was linked very heavily to obesity, and some metabolic syndromes and I’m interested in chronic disease. So I think that was exciting to think that we were tackling into a totally different problem than we were expecting. I think it’s cool that science can take you in ways than you would expect. 

Q: What motivates you most as a researcher? You mentioned that you plan to be an MD-PhD, what inspired you to want to pursue that?

A: I think what motivates me is thinking about the people we’re helping, and that’s kidn of what drew me to an MD-PhD, because I really like working with people and being to help them. My motivation was really solidified when I was here at Yale last summer, doing mostly full-time research, but we also had some clinical opportunities like doing shadowing at a free clinic here. We also did cadaver dissections where we would first look at the cadaver and think about the particular organ system and then a MD-PhD student would talk about their research pertaining to that. For example, we might look at the lungs and then they talk about their biomedical engineering project looking at articifical organ regeneration. This really helped me develop a translational mindset, by taking what I see in the clinic to the lab and try to solve those problems. Because, from my shadowing experiences, I always feel like I was drawn to what we don’t know. I was kind of surprised by how much we don’t know, like even the drugs that we’re using, we don’t know their mechanisms, which is what drew me to the Pharmacology department. I think it’s exciting to take all of those problems you see and then address them in the lab. But at the same time, as a physician, being able to work with people directly, and in a sense, have a more quick response, because research is on a very different time scale. It could be decades before it comes into therapy vs in the clinic when you’re immediately doing something to help someone. 

Q: I asked initially who or what inspired you to pursue science, was there ever a moment at Emory that made you realize that this is the path you wanted to go into?

A: It’s hard to say one particular moment, but I think that my experiences in the Corbett lab as a whole were really influential. Especially when I got to kind of have more independence over my project. I found that was one of the things that fulfilled me in Emory. I always thought it was kind of cool that research could be a job. There were times where it would get stressful, but a lot of times it does feel like work to me, it just kind of fun!

Q: What is one thing you are hopeful or excited about? In both research and life.

A: One thing I am excited about is that I’ve been applying to MD-PhD programs. The process started back in January but I feel like it’s something I’ve been working towards for years. So now finally, that I’m starting to get acceptances– it’s really exciting to think that I’m going to be a physician-scientist and start this journey. And also, hopefully, by Fall 2021, the vaccines coming and things will reset and be a new chapter for me. I’m really excited about that. And in science, there are so many things that I find exciting. I think gene therapy is very exciting. I didn’t realize how far along we are in that. I also think developments in organ regeneration and biomedical engineering stuff is really cool.  

Q: Do you have any words of advice for undergraduate students? In terms of both college, pursuing research at Emory, as well as pursuing a career in research.

A: I would say try to get as much exposure to different things. Pay attention to what interests you, what excites you, what things you like. And keep in mind that, especially when you’re starting out, you don’t have a good sense of all the options that you have. For example, if you get a PhD, people tend to think that you could become a professor or work in a lab. But you could also do science policy, work for a company, or work for the government like the FDA or something in regulation. So there is a lot of different options. And I think that trying to connect to as many people working in different fields and learning about the options is very beneficial. And just trying to pay attention to what you like and following up on that. And getting exposure, both talking ot people and practically speaking, if you can, get into a lab or do an internship, that lets you really see what a particular path is like. The more things you do like that, you’ll get a better sense of what you do like and what you don’t like. And that can help you in trying to figure out your passions. And also, considering what you like and also what you value, what’s meaningful, and what kind of impact you want to have in the world. So just trying to align those two would be very helpful. And talking to your professors, they’re a really great resource. All of my professors at Emory were really helpful and kind. And even if they’re not in the particular field that you want to go into, I think they can still have really good advice and maybe point you to someone who is more aligned with what you want to do.