Episode 01: Alev Erisir, MD PhD

The following interview was conducted in-class, during the Spring 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 Zina Lahham, Erin Morrisroe, and Jess Wang, who also drafted Dr. Erisir’s biography. Editing (for brevity) was by Dr. Adema Ribic. The original recordings are available in Podcasts.

Dr. Alev Erisir is a neuroscientist, professor, and Chair of the Psychology Department at UVA. Her laboratory studies synaptic circuitry and the plasticity of neurons and other brain cells in sensory pathways. During her postdoctoral years at New York University, Dr. Erisir studied the structure of the nervous system using electron microscopy. Since then, Dr. Erisir has continued her research on sensory circuits, specifically the visual and taste systems. Dr. Erisir uses quantitative electron microscopy, tract-tracing, immuno-labeling, and 3D reconstructions to identify the molecular signatures of sensory synapses. In Dr. Erisir’s lab at the University of Virginia, one line of work comparatively studies the gustatory thalamus in the rat and tree shrew. In addition, Dr. Erisir has been conducting studies on the pathology of the aging brain, using Alzheimer's mouse models to analyze the association between ultrastructural molecular changes and mild cognitive deficits in the mice. Using serial electron micrographs, Dr. Erisir’s lab examines how hyperactive oligodendrocytes in mice contribute to Alzheimer’s pathology. Dr. Erisir’s research has made a profound impact on our understanding of synapse development and plasticity and has advanced our understanding of sensory circuit structure and function.

Prof. Erisir, can you tell us about your education?

I went to a medical school, right out of high school in Turkey (I grew up in Turkey). My father was a doctor, so I felt like being a doctor is the thing to be. Not only that, the previous 50 years before me was a huge period of women's rights and seeing more women taking professional roles in society. My grandmother was one of the first secondary school teachers of her generation in the country.

What did you do after graduating?

I worked as a doctor in an emergency room for about a year. And after that, I moved to the U.S. and I started applying to graduate programs. As a doctor, my aim was to have a specialty in neurology or psychiatry. But more and more I spent time in medicine, I found myself having more questions than satisfaction. I really wanted to know why things are, how things can be fixed, and so on. That's why I applied to graduate programs and got into a behavioral neuroscience program at the State University of New York at Stony Brook. And I graduated with a PhD in 1996.

Where did you do your postdoctoral training?

I had several years of postdoctoral training at New York University Center for Neuroscience with a wonderful mentor Chiye Aoki, who was and still is a neuroscience electron microscopy lab. And then I had a very short postdoc appointment at New York Medical College in physiology, where I actually got to practice other techniques as well.

When did you start your position at UVA?

I had a research assistant professorship back at NYU for a year where I got to teach and actually build up that kind of experience before looking for jobs, and in 2000 I got a job at UVA. Initially, it was kind of worrisome because I had spent most of my life in big cities, in Istanbul, and then in New York. And I was worried about how we're going to adapt to Charlottesville. It was wonderful, we came here and loved it. I became an associate professor in 2017, and a professor in 2013. And along those years I was also a co-director for the Neuroscience Graduate Program. I was the director of the Cognitive Science Program for several years, and then the Neuroscience Undergraduate Program. And in 2016, I became the chair of the department. This is my fifth year, and I have one more year.

What do you like about being a Department Chair?

One of the greatest advantages of being a chair was service. I see that as a service to my profession, to my department, to the university and campus. It is a rotating position, so everyone hopefully will be available to do it. What actually I came out with, after five years is that there is incredible satisfaction of getting to know my discipline, my colleagues, and being able to actually do something for them, for my profession, or my department, being able to recruit scientists, new scientists, to the department, being able to arrange new programs and I think there are a couple of other things that I feel I have accomplished in the five years are going to stay with me even when I go back to my microscope again.

Which courses did you teach at UVA?

I have been teaching many courses along the way. My main course lately that I taught for many years is Neural Mechanisms of Behavior. Then the Psychobiology lab, Psychopharmacology, Neuroplasticity seminars. I really enjoy being in the classroom and interact with every generation of the UVA students coming through. More recently I've been teaching Functional Neuroanatomy.

What can you tell us about your past research?

My dissertation project was based on the synaptic circuitry in the visual thalamic nucleus, lateral geniculate nucleus. That yielded a couple of baseline papers that got cited many times and revealed a lot of things about the patterns of connectivity in the thalamus. During my postdoc years at New York University, I continued to learn more techniques about electron microscopy. In New York Medical College, I had a chance to work with a wonderful slice physiologist and we did this wonderful study together and it became an actually quite influential paper since then.

What can you tell us about your research at UVA?

The initial project that I had pursued at UVA was the ocular dominance column plasticity and thalamocortical morphology, a project about understanding how the brain connections change during the early developmental period when the slightest change in the visual environment leads to a drastic change in the connectivity of the brain. I continued to address the ocular dominance plasticity using different paradigms, like premature eye-opening, which leads to circuitry changes and molecular changes in the brain. These are the kind of models that mimic what happens when a baby is born prematurely and is subjected to all kinds of sensory information coming into it without the baby being ready for it.

Are you studying only the visual system?

Several programs and several studies in my lab are actually addressing the brain stem gustatory circuitry in a rat model and several papers came out of that. We have been unearthing a lot of clues about how different sensory systems utilize a similar kind of pattern to process any information, whereas there are some differences that may happen in a chemical system (like taste) versus the classical sensory system like vision and audition.

What other projects does your lab pursue?

One of the ongoing projects (in my lab) looks at another pathway, the pathway coming from the superior colliculus to the lateral geniculate nucleus and for this one, we're using a model of tree shrew. Another ongoing project is about the aging brain and the pathology of the aging brain. This is a question that I actually had a huge interest in for decades, but I only got the chance to actually do it in the last 5-10 years. And the last project that I want to tell you about is the three-dimensional connectomics project. One of the purposes of this project is to be able to identify the patterns of selectivity for different inputs coming from different brain regions, and impinging on the different lateral geniculate nucleus neuron dendrites.

What is your one professional accomplishment that you're most proud of?

Neuroscience is a slow life. And science is a very slow life. Things that you do are usually incremental, and something that you do doing your graduate school comes back 15 years later, and that reminds you that this was very important. A lot of people have used this (discovery) since I was just a graduate student. I had no idea that this was going to have such an impact on science. My dissertation has really had an influence on me later in my career. It brings me back to this nicely studied circuitry in the thalamus and being able to apply it to that other sensory systems.

Could you speak a little bit more about how you discovered your passion for neuroscience, and whether that was when you were in school or after med school? When did your passion for neuroscience begin? And how did you discover it?

I spent a lot of time, of course, in medicine. And, as I mentioned, I was really interested more in psychiatry than in neurology, and in a way, those were actually really cool topics. Being in the medical field, you go into the community and get into these discussions about psychotherapy and so on. And then it's of moving out of these discussions in psychotherapy that I got started to get a little bit more interested in neurology because it is this kind of a subdiscipline that covers a lot of very important disorders. Interestingly enough, a lot of them have no solution. There have been a lot of advances made in the last decades in diagnosis, but not in treatment. It was a lot more kind of a “Yeah, okay, we just diagnosed it, and then we can do nothing about it”. That was one of the reasons why I made a career change basically from being a practitioner of medicine to actually studying the reasons and being in a position to come up with ideas and test them for yourself. That put me onto this behavioral neuroscience program, and after that, I was trying out things.

What's the work that you've enjoyed the most (research, teaching, or being a department chair)? And maybe a little bit why that's the most enjoyable work that you've done? Maybe where too?

It is hard to pick. It's almost like everything amalgamates into your daily life. Maybe being in an academic position I have the opportunity to be able to not do the things that I do not want to do. I kind of concentrate my day, not only 24 hours, but 36 hours of it with the things that I enjoy. Definitely being in the lab is a huge, huge rush, being able to do something, and to see something, find something no one ever has done and seen and found before. That is incredible. You can also make deductions, and you see where else this kind of finding can go, how good it can be, come up with ideas, being able to see patterns, and combining these patterns into different meanings. Those are almost doing puzzles everyday. So I really like doing the research in the lab, and not only hands-on research, but being able to train others. Mentees and students in the lab are incredible, very satisfying interactions for me. For teaching, it is so frightening, but then it's also exhilarating that you're able to interact and be able to transfer some information and put them into a format that others can see. I have to admit my administrative work takes so much time, but at the end of the day, I feel satisfied. The short answer is that I can't really pick one.

A quick question about being a woman in a neuroscience lab. I've worked in (Dr. Williams') lab as the only woman researcher and at first, it was very scary and I doubted my decisions in the lab. Do you have any advice for kind of overcoming that doubt and owning your skills?

You said it: as a woman, (the system) has been improving, but it is hard in any way. You need to be able to set your support system. Reach out to the people like you, that actually can support you at the end of the day and tell you that "Oh, that was that was great". And yeah, self-doubt is fuel. Don't stop doubting yourself. But also know that at the end of the day, what you do is what you do, and you're the first person who has done that. Hold on to that feeling. But it's very important for those of you that pursue these kinds of careers to have a support system throughout life, and keeping good relationships with your peers, in the lab, and forever. Those relationships continue. Two of my (main) collaborators now are my really good friends, my co-workers from my graduate school, with whom I have spent a lot of time on a daily and weekly basis. We have never let go of each other we communicate. So keeping ties with your support system is really important. And don't give up.

As a researcher and as a department chair, what are your thoughts about UVA's current position in terms of underrepresented minorities and women compared to other universities, and do you think there's room for improvement or anything of that nature?

There's a huge room for improvement everywhere. One thing that is happening at UVA in the last maybe 5-10 years is the small glimmers of acknowledgment of how bad things have been. Both at the university level and also at the national level, the ratios of minorities and women in science and the retention rates, are and have been horrible. I'm not going to say that there has been any drastic change in that we're still in that 8% to 12% rate for (leading positions) by women and minorities. It’s even worse for minority women. I think what gives us this glimmer of hope is that the start of an acknowledgment of how bad the situation is. It's also to keep on asking about what can we do about it? What can we do? I do see individual faculty and groups, and the departments are actually taking the initiative to do something about it. There are at the university level plans for setting up the hiring priorities so that they will be more open to hiring minorities, and it is an actual challenge. It's not only whether or not the university can recruit any minorities and foreign nationals or women into its ranks, it is also generating the culture and providing a welcoming environment, both to the faculty and to students that will be coming and congregating here. It is a challenge. But the more I can hear a glimmer of acknowledgment of that challenge, the little bit more optimistic I get. It is also empowering and I see that empowerment in my colleagues as well.

You were talking about how when you were on the path for medicine and practicing medicine, you had more questions than you were getting answers for. And that's why you wanted to go into research? How are you able to get the knowledge that you're creating? And also put it in conversation with people who are currently practicing and in the field? How do you make your knowledge accessible?

It kind of goes again about this idea of how science is incremental. When I was in the emergency room, it was really frustrating not being able to help someone at that point, and knowing that this requires an army of people at every level at every hospital and everywhere to provide that service. When I moved to science and kind of resolved myself, to "Okay, I'm gonna generate this little incremental knowledge", with the understanding that I may never ever see how my little basic science findings get to be translated into a bedside finding and turn into a treatment. But that is the thing, it will accumulate. I will do this and other people are going to do something in parallel at the same time. So a collection of that is going to turn into good for the well being of the people around me. The contribution of the basic science is just someone working on their favorite protein without even thinking what it might be and then ten years later somebody just pops out from somewhere else and says, “this is the kind of a trigger that can actually work as a receptor for the change to bring an alleviation for this issue”. It is almost accepting that I will not be the hero, I'm not going to get a Nobel Prize, but I'm really happy that I can actually put a little pebble in the sea, so that is kind of why I have this as my background.

What made your mentor at NYU impactful and how you've maybe taken those positive attributes and applied them to your position as a mentor yourself,

Very good question. I think of my mentor (Dr. Chiye Aoki) as the person who had a huge influence on my career. She took on that role to, almost in a modest way, be there for me to provide the tools that I might need, and teach me what I need. She also gave me the confidence that (I was) going to do this and you and this is going to be my career. In the simplest terms, the post-doc appointments are going into someone else's lab and working on someone's grant. You finish up that project, basically. The first week I was there, she told me: "so here's the project, I really need you to finish for me. We'll build your papers with that. But while you're doing that, here are also other opportunities, please start collecting your preliminary data and start to pursue your experiments, your ideas on the side". She completely gave that freedom to me. It's not like she told me that I had to use whatever I wanted, she came and helped me to do those things and generate those ideas. That actually put me on the path of getting my own grants and getting my job right after that. I see that strategy quite a bit when I am mentoring my graduate students now. It's an attitude of being there, and being able to support, give people room to grow. Once you're left to do something by yourself, that is where the most change comes, the more you own what you do. That's the point that kind of takes you to the next step. I find my mentors influenced my life quite a bit that way.

In such a long-standing career, what has been the biggest hurdle or obstacle you've faced in your professional career, whether that's academic or administrative? And how were you able to overcome that and move forward?

That actually brings me to a good point that I forgot to mention, what I think is one of the big achievements in my life. So after I moved to UVA, I had two children. They were both born in Charlottesville, they grew up here. That brings out a question of how much of your personal life should hold your career back or whether or not they can coexist. For my life, I had no doubt about that. My career and my personal life can coexist. I had my children, and I was teaching until the last moment and three weeks later I came back and gave an exam. And then I put a couch in my office: my children grew up on my couch. Those are the kind of examples that I have seen. From the postdocs that I have worked with, a lot of the recording rigs usually have a playpen, so that the infant can actually stay there while you're doing your recordings overnight. I think it is a conscious decision to tell yourself that it is okay to bring your life into your career, and vice versa, and let them coexist. You don't have to give up one for the account of the other. I think that is one of the pieces of advice that I can give to anyone who is starting to look forward and worry about how are their lives going to turn out. It turns out fine.

How similar is a tree shrew brain to human, are those layers the same in humans? Which layer receives information or output, and is that the same in tree shrews? And is that why they're being used as models?

There are differences. The principle of segregation of different eye inputs and retinal ganglion cell subtypes in the different parallel pathways is conserved throughout primates. The tree shrew is actually the closest relative to the primates, but the fact that the eyes and the eye inputs and different parallel pathways segregate into different layers holds in this species, so that makes the real good model. The advantage of having a segregated system, in terms of the pathways is that one can study the individual differences between the synaptic connectivity, synaptic circuitries in different visual streams, like the ones in the magnocellular versus parvocellular pathways that process-either the acuity versus the movement and so on. That's why I say different models have their beautiful quirks or the opportunities that are given to us and it becomes a challenge to find what opportunity each model is going to give you and go with that.

You said that you're looking forward to going back into the lab after your Chairwoman position is up. Is there any specific (research) goal that you have for your future?

I showed you those three ongoing projects right now that are carried out by two graduate students. That is actually one commitment I made when I admitted those graduate students, their training, their project, their career is very important. I'm hoping to be able to help guide them through their dissertation. Among those projects, I'm actually really excited to pursue that Alzheimer's brain project, the pathology. Maybe whatever is left in me from the MD days that is interested in the brain pathologies rather than the normal brain, but I find it really fascinating. I think there are really, really important ideas to pursue there, which can actually have a more immediate translational value too in terms of the role of the oligodendrocytes in brain injury. I'm actually looking forward to that.

Back when I was in grad school, we had a lab that used to collect eyelash from every student with nice eyelashes, because eyelashes were apparently the only tool that was soft enough to collect sections. Is that still used in electron microscopy?

I had used it until February 2020. Last year, I told everyone that you cannot use an eyelash anymore because also one of the better tools that allows one to be able to collect these fine things from a diamond knife is your saliva. Everyone has their eyelash tool, private eyelash tool you just lick it and then just guide the fine sections into it. Having a private one is still valid, but I said, “ Okay, we're stopping this. No one is licking this anymore”. It's not going to be as easy to collect these sections, not in the post COVID world.

What do you use now?

The Electron Microscopy Sciences company has the Sabre brushes, so they're very expensive. Eyelash is really easy, you get a toothpick and nail polish and your eyelash, you have your ideal tool, but now we buy Sabre brushes.

This interview was conducted during the Spring Session of UVA’s Hidden Figures class in 2021. Class roster:

Addis, Lucas; Ahmed, Anushey; Akram, Amman; Alam, Maisha; Anderson, Sydney; Bhatia, Rhianna; Bonagiri, Paavan; Booth, Morgan; Clarke, Casey; Fisher, Grayson; Gandhi, Shreyal; Hossain, Mohammed; Rayan; Jensen, Kate; Kim, Michael; Lahham, Zina; Lea-Smith, Kori; Leffler, Schuyler; Leventhal, Emily; Mehfoud, Matthew; Morrisroe, Erin; Pham, Twindy; Sajonia, Isabelle; Sisk, Emma; Suram, Ananya; Wang, Jessica Beth; Webster, Tessa; Wilson, Gina. TA: McDonald, Amalia. Instructor: Ribic, Adema, PhD.