Episode 34: Ileana Hanganu-Opatz, PhD

The following interview was conducted in-class, during the Spring 2024 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 Gennese Evelyn Springs, Shevya Panda, Danna Emad Jaber, Nicholas Shelburne Manspile, Vyizigiro Foste, Johnny Azizi, Anna Love Kleppin, Jade Mountain Girl Strand, Kaitlyn Reilly Money, Julien Siguineau Brutus, Neal Dhar, Kendall Ramsey Cox, Bianca Cruz Alinsonorin and Caroline Alice Wynne, who also drafted Dr. Hanganu-Opatz’s biography. The final editing was by Dr. Adema Ribic.

Dr. Ileana Hanganu-Opatz is a Professor at the University Medical Center Hamburg-Eppendorf and the leader of the Institute of Developmental Neurophysiology. She completed her undergraduate work in Romania, studying biology and biochemistry, and has gone on to complete her graduate studies in Germany. Dr Hanganu-Opatz studies brain development in health and disease, and is an expert on the development of sensory and prefrontal cortices. She received the Du Bois Reymond prize in 2008, and is a recipient of a Consolidator Grant from the European Research Council. Dr. Hanganu-Opatz is also a member of the FENS Committee of Higher Education and Training Committee (CHET).

Was there anything from your upbringing that fostered your interest in studying neural physiology? Is there a reason that you’re interested in pathophysiology and their relations to mental disorders such as schizophrenia?

I don't have a personal reason, except [for] the fact that, when I was, I think in high school, I read a book written by Solomon Snyder that describes the limitations of treating mental disorders. Despite the fact that my high school [experience] was some decades ago, I would say we still have the same problem, and the knowledge gap still persists. 

What was the scientific community like growing up and studying in Romania and Germany? Was there any person or experience that shaped the person you are today?

Many people influenced my career positively and negatively.  I started in Romania and I knew I wanted to do research. Even though I started in biochemistry, I'm now a physiologist because I had a fantastic physiology professor who let me go to the lab and do small projects. This was Professor Maria-Luisa Flonta, from the University of Bucharest, and she was really impressive in recognizing young talents. I wish to be like her-she was already quite senior at the time I met her and was the person who let me give a scientific talk for the first time.

What were some of the positive influences? 

I got a fellowship in my last year to do research, and I had the opportunity to choose where to do practical work. There were several labs all over Europe, and I chose Hamburg.

I did my experimental work under the supervision of Jürgen Schwartz. I realized one day that I was simply doing something somebody else had done before, and then I went to his office and asked him, “I want to do something that nobody’s done before.” Looking back, it's was a bit arrogant-I was 21 at that time.

However, he gave me a project that used the patch clamp technique. Many students tried to get a seal on this cell [that Jurgen was studying], but because they were so small, they were immediately sucked into the pipette. I spent many days and nights trying to do this, and on my birthday, I managed to get one seal from those cells, and it was my first publication. He [Jürgen Schwartz] was an important person in my life because he said, “Try. Maybe you manage. Maybe you fail, but try.” 

What were the negative influences?

One of the first sentences that I remember in my first year at university was from a professor: “What do you want to do here? Females don't belong in science work.” I was not upset at that time, but I realized later that female scientists were not as well seen as male scientists. 

This person showed me [that] as a female, you don't need to be angry. You just need to reply quietly and say, “Well, this is how it is. I will prove to you that I can do good science as a female,” and I think every female scientist knows this. I'm married to a scientist also, a Professor, and I know how it is for him, so I think these negative influences exist for both.

Your laboratory is split into different teams: juvenile development, neuronal processing, mental disease, and cognitive olfaction. Do you have a favorite team or area of focus? Why?

They are all fantastic! If I had luck in my scientific career, it was because of my people. Maybe [it’s] luck, maybe [it’s] also a bit of education, [maybe] it is enthusiasm, [but] whatever it is, these teams, especially the team leaders, are amazing scientists. Maybe it’s not clear from the website, but [it’s] not only my intellectual contribution to these teams, but it's also their input, their ideas, their thoughts. 

I am most familiar with very early development-it is something that I started with. I established several techniques when I was a postdoc, including recordings in very young animals; so this is something that I can do hands on. On the other hand, I admire the team that I refer to as the math team. They develop all the modeling strategies and analytical tools. I must say I'm admiring them and try[ing] to understand what they are developing, but I'm not able to do what they do. I can understand and guide them. I can ask smart questions, or maybe sometimes stupid questions, even if they don't exist. Or, [ask] questions that may be a bit lower level. I [acknowledge] how politely they answer these questions when I don’t understand. I think this diversity of expertise is important-I don't think I'm the boss just because I'm the godfather here, but simply because I have more experience in the field. 

In one of your collaborative studies, you examine the resting-state theta-band connectivity of high-risk individuals in regard to schizophrenia using EEG. Can you tell us a bit about your role in this research, and share your thoughts on the potential of EEG microstate analysis?

This study is an example of the collaboration that I’ve had [for] many years with Christoph Muler, a psychiatrist. I am not a medical doctor, so I am not allowed to record the patients. Of course, I was there when the recordings [had] been done, but the German laws are very strict. In this study, together with my team, I provided the analytical tools. 

I believe that EEG is completely underestimated. If you ask me, I think that we[‘ve] looked at EEG [for] so many decades—centuries, almost, since Hans Berger developed this technique— and we still don’t understand exactly what’s going on. For decades, we were focusing on a very artificial separation of rhythms that emerged historically. So, we have alpha, beta, gamma. They are called this because they are observed first, second, [and] third. Even the classification of EEG, it’s a bit… old fashioned, so we have no clue what’s “behind” [it]. We understand now, a bit, what gamma [is]: gamma emerges [from] pyramidal [neurons] to interneurons, and so on. EEg also has something that we call very often “noise”, but very recent studies show that this “noise” gives information about the level of excitation to inhibition. Interestingly, one can look at this “noise” and predict whether the “noise” comes from [the] EEG of a patient, or of a normal person. There’s [been] an explosion of studies in this direction of prediction in the last two years. I believe EEG is a very good tool. 

Based on your research about olfaction and cognitive development, could the loss of smell be connected to the long term brain fog associated with long term Covid?

This is a topic that I’m not an expert on, but I have a good friend, Matt Grub, who contributed to a study that directly investigated the influence of long COVID-19 on smell, and how smell processing, or lack of smell processing, can affect cognitive domains. I can only tell you what I know from their studies, as well as what others have looked at. The problem with smell is that it bypasses the thalamic nuclei, and goes directly to the limbic system. This makes [smell], as a sense, very particular. If you compare it [smell] with hearing or with vision, where it [hearing or vision] goes through the thalamic nuclei and then goes to the neocortical area, smell just goes directly [to the limbic system]. It is clear that if you have a [smell] deprivation over time, which can be caused by many different factors, it might, or should have, an important effect on the downstream areas, such as the hippocampus and prefrontal cortex. It is clear that if during long COVID there is an impairment in smell, this should have an impact on the processing of information in the higher order, cognitive areas. It has been shown that it has, and it’s probably very long, if not irreversible, depending on age. The older people are, the more difficult the recovery. On the other hand, smell deprivation during development has dramatic effects on the maturation of cognition. This is what was shown recently in a study done last year by one of my PhD students. Smell and cognition are tightly related.

Your study on subplate cells as amplifiers of neuronal activity examines the role of subplate neurons in afferent and intracortical activity. Could you elaborate more on how this study arose and what this study was like? 

The subplate cells were the cells that I worked with during my PhD and first post-doctorate stage. I think that at that time [the sublate cells] were very popular. I realized over the years that now they are getting more popular, but there was a big silence period on subplate research for a while. These neurons are present at a specific developmental time window and they seem to guide the thalamic axons towards layer 4 in the neural cortex. In my research, this was the somatosensory cortex. 

What did your study on subplate neurons show? How did/will this discovery contribute to further discoveries on neuronal processing? 

We showed that subplate neurons did more than guiding axons. Their role is to be a template for how the cortex will look later on when it’s finished. Whether the study was relevant for the field later on, I don’t really know. I had the impression that after this study and several other very nice studies, this research went away, but now it’s coming back.

Your lab has identified that prefrontal-hippocampal communication is a hub of disease induced impairment and that its decoupling at the neonatal age is a fundamental mechanism underlying the pathophysiology of schizophrenia. Do you believe that this is a reliable model of drug action?

I get asked very often what my biggest dream in science is and I think that this is one of the dreams I have. For schizophrenia, there is absolutely no treatment for cognitive impairment. People treat schizophrenia, bipolar, and other diseases, but they treat the psychosis. The problem is that they still have cognitive impairment and this is not treatable. We have absolutely no drugs for that. I hope that if one identifies regions, cells, receptors, or synaptic processes that can be addressed by drugs, one could have a better access to the disease. However, as a neurophysiologist, I am an observer-I am only looking at what a neuron is doing. I can manipulate it very artificially with optogenetics, add some electrical currents, but I have absolutely no possibility to develop a drug. What I can provide, together with many other teams, is information about targets that are amenable to therapies later on. It is a small step, but it’s a step. 

How possible would it be to rewire the prefrontal cortex in humans? How much more complex is it than in mice?

I think that the idea of rewiring the prefrontal cortex comes from humans. It is a beautiful hypothesis with absolutely no experimental proof. The first [to discuss this with me] was Wolf Singer in Frankfurt, a godfather of oscillations and synchrony. He told me, "Well, development is very important, but if you missed the chance to educate the child during the first years, don't worry. You still have an opportunity during adolescence, because then everything is reorganized, and then maybe you have a chance to have an impact on the networks that are changing.” I asked him, "What's proof for that?" He said, "Well, I don't know. This is psychology more than neurophysiology.” We then started to look [at] mice to try and get an experimental proof for this theory.  We studied this in mice and we observed not only that there is a reorganization, but we also showed how this reorganization takes place, and what the consequences are. We also showed that this reorganization is controlled by microglia, the immune cells of the brain. What surprises me a lot is that microglia are telling the neurons, “Okay, now you have to reduce.” And yes, apparently all mammalian species have this make, break, rebuild, and humans probably have it too.

Now, the 1 million dollar question is, why? It makes no sense, energetically, but I suspect it has a lot to do with sex hormones. 

How do you stay updated and integrate new technologies or methodologies into your research?

We have a question and then we look to see if a technique is available. Sometimes, we don’t have the technique so we forget about the question or postpone it, maybe somebody will develop the technique. Otherwise, we develop the techniques too, in case we are able to do it. I have to admit that most of the updates come from my teams. 

You’re involved in the science policy space both nationally and internationally, how do you think the government and policy can help facilitate innovation in the scientific field and how have you seen government perception of science change through your career?

I started in a country where the interest for science at the political level was relatively low. I was in Romania after the breakdown of Communism. Everything changed, and of course the priorities were not investing in education and science. This also led to a brain drain in Eastern Europe. I’m one of those people who left Romania, despite an excellent education that I received I went to Germany and had a totally different experience at that time. It was like Paradise. There was a lot of money in the system, funding for many projects, and fantastic support for young generations. I have to admit, I am sad because this is not the case anymore. It has changed and it’s related to how politicians perceive science and what they consider important science. It has something to do with the parties too. Climate change is now the most important subject for politicians. I fully agree that it’s very important but the question is whether science should be focused only in one direction, and not on the diversity of the scientific world. I think that [diversity] is very important for all of us.  There is also less money in the system, and less money leads to fewer possibilities for young people. For example, in the European Horizon 2020, Neuroscience was not even mentioned by name. How can you have an initiative on science without neuroscience? We were really shocked about this. They changed it, but these are just words, and I don’t know how we will see it in money or other forms of support. 

Given your role as a PI and professor, as well as your membership in multiple research and ethical committees, what would you say is your favorite position that you’ve had? Why?

One function that I enjoyed was being the founding member of this young neuroscientist network of excellence, FENS Kavli. It was funded both by the Federation of European Neuroscience Societies, as well as by the Kavli Foundation, and it was initiated by the idea of the Kavli Foundation saying, “We need to somehow, [find] the next generation leaders in neuroscience.” We’ve been established for almost 10 years, and I was one of the founding members. It was a very nice experience to sit with 20 people in one room in a castle in the UK, somewhere in the middle of nowhere, just brainstorming. 

What is one thing you wish more people knew about the work you do? 

People know that I work on development, and they ask me, “Well, do you think that the brain of the kids nowadays is different from the brains that they had 30 years ago?” The first time I heard this question, my response was: “What? Evolution is not so fast.” Later on, I realized that this is a general opinion. I would like to clarify that it's not a problem of the kids, but of education. People began relying on genetics too much, and are not establishing the proper environment-education-for children to thrive. This requires time and requires effort, so it’s easy to not do it. This is also one important aspect that I would really like to see more promoted, to convince parents that even if it's exhausting, it is incredibly important. 

You are a member of the Committee for Higher Education and Training (CHET) of FENS (Federation of European Neuroscience Societies), working to help develop training programs that quote, “optimally fit the needs of next-generation scientists.” What, in your opinion, should be of utmost importance when it comes to training young people who want to become scientists? What advice would you give to early-career researchers interested in pursuing a career in neuroscience or developmental neurophysiology?

The answer is very simple because I give it very often. Listen to your heart. Think about what makes you the most enthusiastic. What is your genuine interest? Do it! Don't care about what people say. What is timely? What is good for you? What fits your skills? Whatever you're interested in, if you, as I call it, burn for something, then go for this.

What do you think are your most significant accomplishments or contributions in this realm of research, subjectively?

In my research there are 2 achievements that I consider significant, one is the paper we published in 2020 in Neuron. [In that], we showed that the miswiring of neural circuits in animal models of schizophrenia is caused by hyperactive microglia. It was the first time I linked [neural] networks with microglia. It is not my achievement, it is the achievement of a very talented PhD student who is on the way to become an independent PI. We have now started the first study with clinicians based on the results of this study. 

Other achievements that I personally have are certainly on the ERC, big grants and the fact that I built my own lab—this is something that I really achieved.