Episode 12: Michelle Antoine, PhD

The following interview was conducted in-class, during the Fall 2021 session of Hidden Figures: Brain Science through Diversity, taught by Dr. Adema Ribic at the University of Virginia. What follows is an edited transcript of the interview, transcribed by Chloe Posner, Caroline Luscko, Julia Pappagallo, Liza Ware, Ryan Murphy, Zainab Faisal, and Elizabeth Fastow, who also drafted Dr. Antoine’s biography. The final editing was by Dr. Adema Ribic. The original recordings are available in Podcasts.

Dr. Michelle Antoine is an Earl Stadtman Investigator and the Acting Chief of the Section on Neural Circuits in the NIAAA. She completed her postdoctoral training as a Miller Research Fellow and a UC President’s Postdoctoral Fellow at the University of California, Berkeley, in Dr. Daniel Feldman’s laboratory. Dr. Antoine’s postdoctoral research redefined the classical notion of excitatory-inhibitory balance and its role in autism. She continues to study the synaptic and circuit pathways that contribute to nervous system disorders, ASD in particular.

Dr. Antoine, where did you go to school?

I was born in the Caribbean, on a small island called the Republic of Trinidad and Tobago where I went to an all-female high school. My high school was called Bishop Anstey High School. I was surrounded by a lot of girls my own age with different interests. More importantly, we had a lot of female role models. Overall, I think it was a very positive environment for me. I learned to believe that I could truly pursue science as a career, but I think that the idea of what it meant to be a scientist or a biologist was extremely limited. For me, it meant that you taught at a university and did research or benchwork in the context of a textbook or lab class. I wasn’t able to visualize it as I couldn’t see people who had jobs as research scientists.

When did you first have exposure to science as a profession?

As an undergraduate, I was first exposed to research through the Howard Hughes undergraduate program. I got to spend every semester in a different lab until I found that one lab and professor where I felt like I belonged.

Was that when you decided to be a scientist?

Even during college, I definitely know I wanted to be a scientist. Perhaps I wanted to be a professor, but the institutions I was at weren’t research-heavy institutions. All the intricacies of being a scientist and being a professor weren’t fully known to me until I went to graduate school and I could see what the scope of being a scientist entailed. At that point, I was able to make a more informed decision because I know what all the elements were. That’s when I fully decided to become a scientist.

For many students, medicine is usually the primary path versus going straight into biology or another science. What made you go into science? How did you decide between science and medicine?

I liked the challenge of science. I actually think my parents wanted me to be a physician. I went through the process of enrolling in pre-med classes, but I really enjoyed the challenge of science. In science, you're always searching deeper and trying to find the answer, whereas in medicine, it's always kept as a mystery where something works but you may not know why. Science was about the challenge of knowing why, the logic of it, and the ability to trust that the logic was based on a firm foundation of understanding.

What was your major in college?

I majored in Biology and Math, although, if I could redo college I probably wouldn't do biology-I’d do business administration or something different. I think I would have liked to really take advantage of the liberal arts education because I was very focused on doing science, and I stuck to what was safe and what I knew. I think I would take more chances if I ever had to go back to college.

What did you do after graduating?

After graduation, I went to graduate school at Albert Einstein College of Medicine. If I could choose a role model, Einstein would be one of my role models because science is super complex and there are many elements to it. There is an administrative side, a social side, and an oral and written side of science, so different people can serve in different capacities as role models. Because of this, I have several role models. However, in terms of grit, in terms of persistence, in terms of “this is a great man that did marvelous things very early on despite the fact that having very little support from his family”, he’s one of my role models. Einstein really had to power through and stay true to his convictions.

Was that why you chose to go to Albert Einstein?

I think that I had the choice to go to many other places, but I chose to go to this school because it was a great fit for me. The environment was very collaborative and I knew, somehow, that it would work for me. I liked the idea of being untethered or free to do what I want to do, and it seemed that they would allow me to do that there. I chose this school because I thought that I would be able to do what I wanted to do and learn the way I wanted to learn, which was learning from many people in a somewhat non-structured environment. I didn't want to go through the process of learning in the manner of a recipe; I wanted to make my own path in a lot of ways. I joined a lab that studied involvement and brain patterning, specifically how the brain develops and the early signals that ensure that different regions of the brain are specified. I knew right away that I didn't want to do that, I wanted to do something else.

You switched the research topic?

I wasn't sure how I was going to do it when I joined this lab, but I think it was just a matter of serendipity because I got these mice from Gord Fishell’s lab. I started breeding the mice and realized that some of the mice were really small and some of them were super hyperactive and running around, and I wondered what was wrong. Then, other people saw them and they were like, “What's wrong with your mice?” They were just circling like crazy and they looked, to paraphrase, like they were psychotic. My mentor asked, “Why don't you just find a gene that's causing this? It’s just a gene.” I thought that if it's a gene, then it's definitely disturbing something in the brain and that's why they're crazy. What we ended up finding out was that the original defect wasn't actually in the brain, it was in the ear, in the peripheral nervous system, and those peripheral inputs were shaping the nervous system function.

That’s a very surprising finding! Can you comment on it more?

This finding was shattering in many ways because I initially thought that if there was something wrong, it must be the brain since that is where everything starts. Then I realized that it was actually a sensory problem originating in the peripheral nervous system that would produce these symptoms traditionally classified as autism and ADHD. That was one of my biggest findings.

What did you do after that?

For my postdoc training, I went to the University of California Berkeley and I did research in Dan Feldman’s lab. The opportunity to go there came from a Miller Research Fellowship, which gives its research fellows a three-year opportunity to do research at Berkeley in the lab of their choosing, and, of course, they funded the research. I knew I wanted to learn electrophysiology and view the brain not just from a genetic and molecular standpoint.

What are some highlights of your postdoctoral work?

The highlights of my work there took me back to graduate school! I thought we were just going to prove what we already knew or at least lend support to what we already knew: that balance (between excitation and inhibition) was really a major driver of autism. What we ended up finding out is that, yes, hyperexcitability in autism can exist, but it may have a beneficial role for the brain.

What is the main research topic in your lab?

I started my lab in January of 2020 and the main research topic is the lab circuit function in normal and diseased brains. We look at circuit function from the lens of different diseases like autism, or intellectual cognitive disability. Our first paper that's currently in preparation is all about the phenomenon called a fever effect in autism. People who have autism have symptoms or display symptoms such as cognitive impairment and sensory abnormalities, repetitive behavior, hyperactivity. It's a disorder that starts very early, from as early as six months old, so we know it's some kind of neurodevelopmental disorder. For many individuals, it can be quite disabling. We have very limited treatments for it. Most of the drugs that we have at least are FDA-approved drugs to treat autism, but it doesn't really treat autism symptoms specifically, it treats irritability. In 1980, there was a large group of children out of a therapeutic war in Bellevue Hospital in New Jersey and New York. The doctors noticed that the children who had autism got better when they had a fever. There are many anecdotal reports, and these reports were chronicled in an article in 1980. There's very little research on understanding the reasons behind having a fever. We did our own research in my lab to add to the understanding of it. We found that a fever can work to improve cognitive function in people with autism because it essentially reduces activity in the network. The fever quiets the entire system, and it seems to help improve symptoms.

How has your work evolved over time?

I started off looking at disease and trying to understand the disease from the perspective of genetic and molecular mechanisms. Then, I explored these diseases from the perspective of neurophysiology, and now we're merging the two worlds. We're also focused on understanding systems and looking at system functions from the perspective of multiple circuits.

Have you had any non-research roles?

I think for a very long time I was really quite content just doing a lot of individual type services. Non-formal roles that were all centered on service were an important part of my high school upbringing. It was stressed to us that we should serve our community, so I've always served my community. I volunteered at the food bank community and worked on beautification projects. More recently, I have worked on providing safe spaces for students to learn science. As an tenure-track investigator I feel that my contributions have now become more formal. I am part of the equity, diversity, and inclusion (DEI) committee. I have an official title, and I am an editorial board member at eLife.

Have you published work outside of your own field?

One of my research papers that I think is really far out there, even for me, looked at the origin of handedness. It's not a popular paper, but it was truly very different for me trying to understand why one fifth of children who are twins can have different dominant hands. They're supposed to be genetically identical, and handedness is supposed to be something that we think is due to genetics, but here are these genetically identical individuals where one is right handed or left handed, or ambidextrous, and they differ. I ended up collaborating with researchers, who only work in research on humans and people, that I would never really normally interact with. I think that was a very challenging time for me, and it produced something that was really outside of what I would normally do.

Do you have any other interests and hobbies that you enjoy?

An interesting tidbit is that I do like to cook. I like to explore nature and hiking. I’ve never actually gone camping so that’s on my list of things to do. I’d like to just go somewhere off the grid and just stay there for a week.

You stated that you have worked on providing safe spaces for students to learn science. Could you elaborate on how these spaces have been used to increase diversity and women in STEM?

The idea for creating safe spaces was part of the Inclusive Cell Biology program at UC Berkeley. In classes, women and minority students frequently feel a bit restricted in terms of their ability to open up in terms of questions. There are many things that they might know, but they don’t feel comfortable to ask these questions during class time. The idea was to create a safe space after formal class hours where we can go over the lectures and remove some of the pressures and burdens that are placed on students.

Can you elaborate more on this?

Many times, they might feel as though they represent an entire group when in reality they are just an individual. The idea was to remove some of this burden by altering the composition of the groups so that people can ask questions and get answers to their questions. There were no formal restrictions on who could attend, but we wanted to remove the idea of judgement and group characterization and just provide a space where students can just ask any question they want regardless of how they think it might be perceived. Most of the students who participated in these classes were women and minorities. As founders of the program, I don't know if we have enough data to know how successful the program has been in terms of keeping students in the STEM fields, but it would be interesting to look back in the next few years to see how many students this program helped.

Growing up, did you feel you had an ample support system, or do you feel you could have had someone to look up to or more opportunities growing up?

I should start by saying that I’m naturally introverted. From a very young age, I spent a lot of time alone by choice. I gain a lot of validity from within. In terms of support, I’ve always looked within myself for support. I’ve also been lucky since I’ve encountered some really amazing teachers. Teachers are unsung heroes because a great teacher can really change your life. The enthusiasm they have for you and the class can open your world.

How did you do in grad school as an introvert?

I was lucky when I was in grad school because I’m always the person that doesn’t follow the trends, and I’m always that oddball person who is not in the crowd. In my graduate school, I didn’t really get support from my main department since I was doing molecular biology and genetics in the neuroscience electrophysiology department. Along the way, I gave many talks to other departments where I thought they would be more open to what I was doing. From these experiences, I was able to attract two professors. With one of them, I felt that I could go to him with problems, and he was actually one of the first people that proposed a way of what I was doing that actually worked on the first try. Meeting people like him who fuel my career are the support. I think in my postdoc years there weren't many people there that I could look to for support. But, I think once you anchor your mindset, determination, or drive from within, the people that come into your life are necessary, but you still always have support of your own.

Your main niche in research was on ADHD and Autism. What drove you to get into that field of study?

I didn’t plan my field of study. Instead, I just stumbled into it. I let science guide me, and that’s one thing I love to do. When I went to the University of California Berkeley, I actually wasn’t planning on studying autism, but I was planning on dissecting the circuits that are involved in how the peripheral nervous system contributes to the central nervous system regulation. However, I joined Dan’s lab and he was psyched at the time about the links related to autism. He suggested doing this project on autism, and I thought that would be a pretty good project. It was a good way for me to do what I wanted to do, which was to learn physiology. That was my key goal, and I honestly would have done anything. I wanted to gain a tool that I could apply to the questions that I wanted to understand and answer.

Did having the only male teachers in your school be teachers for STEM classes make you question how or if you could succeed in that field as a woman?

No, I realized today that my only two male professors were my math teacher and my physics teacher. All of my other teachers, my chemistry teacher, my biology teacher, my math teacher, were all women. I think that since the men were a minority, their impact was minimal. It seems strange, but that's really the honest truth because everyone else, especially in dominant roles such as the principal and vice principal, were women. So, it didn't really make me question how or if I could succeed in the STEM field.

Since this is an upper level psychology course, a lot of us have strong backgrounds in the social sciences versus in say biology or neuroscience. With that said, a lot of psychology is focused on abnormal behavior and how the environment plays a role in its development. Do you ever get criticisms from psychologists or scientists that focus more on epigenetics or environmental influences?

Yes, I think I got criticism. When I was in graduate school, my home department, which was neuroscience, wasn’t very supportive of what I was doing because they didn't study disease from the same perspective. Their perspective was studying disease from neural circuit function. I got remarks where some people would say “You're doing psychology work. You're not really doing science,” and actually the Chair of the Department told me this right to my face. At the time, that really did affect me. You think your work is valid, but then there’s this person that’s telling you that it is not. It set me off on a journey to do what they were doing, but better. I then started to do hardcore neuroscience. Ironically, they are now doing what they called “psychology research.” I should remark that this has been their most successful type of research to date since it has gotten them more funding than they have ever gotten in their whole career. It goes to show that sometimes the things that people tell you may hurt for a little bit, but you just have to put it in some kind of context where you realize it's their issue.

Since you have a background of a lot of female teachers, when you entered into the graduate world, did you feel any pushback or aggression from your male peers and teachers? If so, did you power through it?

I most definitely did. I think what motivated me was finding strength from within and specifically, finding a space where what I was doing could be given a fair evaluation or a fair shot instead of being put down from the start. Once I entered that safer space, I was able to meet male investigators that were completely different from the ones in my home environment. This gave me the strength to power through being in my home environment, knowing that there was validation in what I was doing. You just have to power through it, but it shouldn't be this way. Many of us are working to change it, but it is this way, so you have to adapt for now. The beauty of it is that it worked out for me. I just stuck with what I was doing, and when I had a final product, the successful people wanted to give me some kind of validation. It's really good to always keep a little bit of that validation from within because that is not guaranteed. But yes, it's difficult.

How did you find a balance between maintaining your commitment to service while navigating your career path?

I was given the message of service so early in life that it became part of my fabric as a human being. It is something that I need to do. I would say that I've always tried to do service, but quite honestly, the balance shifts depending on the immediate need or your immediate goal. For example, let's say that I started college with 10 service projects. By the time I got to a postdoc, I was doing two service projects. I wouldn't say that I necessarily had a great balance, but it was the balance that was needed at the time because I had to focus on my main goal, which is to become a professor. At some point, when I become a professor, the opportunities for service will show up and I will embrace that. I don't make it a 50/50 commitment. I think it really depends on what I'm doing, but I try to work service into my life. I don't think you need to feel that you have to devote eight hours to something every week.

What kind of advice can you give to prospective students who wish to pursue medicine but also want to find time for outside passions?

For students who want to pursue medicine but also want to find time for outside passions, I think you really have to know yourself. I think you really have to know what you need. For me, I need to feel like I'm giving back to somebody, and I can’t spend five years not doing anything. So I need to fill the need to help the external community, but I need to fill that need from within as well. I think it's always good to have your passions, but the problem arises when your passion starts to get in the way of your other goal of pursuing medicine. There is always some kind of outside factor that reminds you to readjust your balance, and it is okay to readjust your balance so that you can pass your medical school classes or complete sufficient preparation that will get you into medical school.

It is very impressive how long you were in school and how you continued doing a research fellowship at UC Berkeley, and I was wondering if you were ever discouraged by how long it took you to finish Howard Hughes Undergraduate Program, Albert Einstein School of Medicine, and then a postdoctoral position at UC Berkeley?

I think it's a passion for me, and I also had this burning desire to find the answer. When you have that, it just drives you. Obviously, you're doing science, you're going to be discouraged along the way. I was discouraged very early when I worked on something for three long years. Initially, we had this idea that the abnormal behavior in an animal was due to genetics because we crossed animals containing a particular genetic alteration. It turns out that that gene had nothing to do with the phenotype whatsoever and I had to start over. Many of my professors suggested, “Oh, you should just write it up and graduate.” Of course, I was sad. I went home and I had a good cry about it. Then, I realized that I have to pull myself together and start over because I really wanted to know the answer, and I knew that it was super important.

How did you overcome that discouragement and stay determined to continue your passion in biology research?

You can get tunnel vision, and you should have tunnel vision in some ways, but you should also always focus on your end goal. Since my end goal at the time was to be a professor, I knew if I didn't do well in grad school, it would just be harder to make up for that. Every stage of your career, you have to try to do the best that you can in order to get to where you want to be in the future. I knew I couldn't fail, and that was enough for me to wake up and continue along the way. It's okay to be sad and it's okay to be discouraged, but keeping your focus on your end goal really helps. If you're passionate about what you're doing, then time is of little significance because you are driven to find the truth. That's why there's a stereotype about scientists being in a basement for years. They're doing something they really like to do.

Additionally, after being in school for that long, what made you want to continue pursuing a career in independent research rather than college education?

I thought about a career in college education as opposed to a career in independent research because I really like the idea of educating young minds and helping them to learn how to think critically and be independent. However, I think doing that alone wouldn't be enough for me because I felt like I got a little bit more energized from doing research and just observing things and trying to figure out how things work. So, it's that energy and that challenge that made me decide to do research.

Has it been challenging to collect and gather empirical data to support your research and findings?

A lot of our observations in humans are simply associations, or correlations, because for ethical and moral reasons, we can’t go in and lesion parts of the brains of humans in different areas. We have more methods now like deep brain stimulation and so forth that one could argue as being human optogenetics. But, you still can't do it at the same frequency that you can with mice. Mice represent a way in which we can translate our ideas of the mechanism in humans, which we can’t always do, in mice. In terms of finding data, I am always open and willing to collaborate with people that do human research, and I tried to start all my research with a finding in the human population, and seeing whether I can replicate that particular phenotype as much as possible in a mouse. But, it will forever remain an open question whether what you find in mice is relevant in humans, even if the phenotype looks as close as possible to the mouse.

Could you elaborate or tell us more about times you’ve felt personally marginalized in academia and how you’ve overcome these situations?

There's been many times where I felt marginalized in academia and I don't think that ever goes away. For lack of a better phrase, it has been one of the dark consistencies. It's been like this since graduate school, and I think that it was the worst at UC Berkeley and now I'm fine here. I realized that a lot of the marginalization or statements that people make or the things that they do that can potentially or actually make you feel marginalized are due to them not being aware or not actually having an intention to do that. Some people do have an intention and some are just not aware. For me, it's getting that kind of validation from within and surrounding yourself with people that value you, as well as keeping your eye on your ultimate goal. That's how I overcome these situations.

Could you tell us about the role you play on the diversity, equity, and inclusion committee, and what the committee is involved in?

The work that I'm doing is primarily centered on creating a program that bridges or integrates the community into our daily operations. We really want to get to a space where the walls of our institution are so broken down so that we have a lot of different trainees here of different ages that we are interacting with in the labs. There are many of these bridge programs at the NIH where institutions can capitalize and form true formal relationships with the NIH to use their resources and train their students. These institutions tend to be the institutions with a lot of financial resources, the prestigious universities as you would say. Right now, I’m trying to make it more inclusive but adding some other universities to the list that may not be as prestigious, but that I believe are also valuable institutions with really smart, driven, bright students.

 This interview was conducted during the Fall Session of UVA’s Hidden Figures class in 2021.

Class roster: Brink, Julia Elizabeth; Abraham, Carly Elizabeth; Rose, Odell Bayou; Kang, Elizabeth; Posner, Chloe Grace; Luscko, Caroline Ann; Pappagallo, Julia Dominique; Ware, Liza Elizabeth; Murphy, Ryan Martin; Faisal, Zainab; Fastow, Elizabeth; Walker, Mary-Catherine; Petz, Kaitlyn Dorothy; Terblanche, Alexandra Savenye; Nguyen, Katie; Guttilla, Gianna Marie; Hoang, Chloe Nam; Grace, Ann Brown; Smith, Charles Cornelius; Sears-Webb, Delaney Jean; Abed, Jamil; Miao, Julia Stephanie; Johnson, Catherine Anne; Kim, Evalyn; Lee, Sarah; Pietsch, Maggie Malia; Cheng, Kaitlyn Jiaying; Freud, Jordan Maria; Patel, Sonia; Silbermann, Katherine Elizabeth; Lumpkin, Justin; Lemley, Rachel Ann; Hall, Maria Elizabeth; Nugent, Elise Genevieve; Limon, Safiye; Mangan, Erva; Ali, Sophie; Muse, Morgan Noelle; Miley, Sareena Elizabeth; Bennett, Bailey Grace; Mollin, Hannah Beth; Nguyen, Daniel Van; Englander-Fuentes, Emilu Maria; Pest, Marshall Sinclair; Mahuli, Rhea Mina; Chindepalli, Jahnavi; Malyala, Meghana; Weldon, Nathaniel Andreas; Aschmies, Lindsay Elizabeth; Chakrapani, Krithi; Heintges, Bella Grace; Baker, Gabriella Christine; Bonsu, Tenneh Ina; Hall, Ann M; Rodriguez, Kaitlyn; Simmons, Emma Isabela; Davenport, Julia Barrett; Andrews, Tara; Ramirez, Alexa Hidalgo; Petrus, Sarah Anne; Singh, Aanika; Wilson, Sydney Paige; Younan, Krestina.

TA: Kipcak, Arda. Instructor: Ribic, Adema, PhD.